From The MPG Institute for Plant Breeding Research[MPG Institut für Pflanzenzüchtungsforschung](DE): “A two-step adaptive walk in the wild”

From The MPG Institute for Plant Breeding Research[MPG Institut für Pflanzenzüchtungsforschung](DE)

May 18, 2022

Angela Hancock
Max Planck Research Group Leader
hancock@mpipz.mpg.de

Dr Mia von Scheven
Head of Public Relations and Outreach
+49 221 5062-670
pr@mpipz.mpg.de

New research in plants that colonized the base of an active stratovolcano reveals that two simple molecular steps rewired nutrient transport, enabling adaptation.

An international team led by Angela Hancock at The MPG Institute for Plant Breeding Research[MPG Institut für Pflanzenzüchtungsforschung](DE) and including scientists from The Victory Project[Associação Projecto Vitó](CV) and Fogo Natural Park (Cape Verde), The University of Nottingham (UK), and The Ruhr-University Bochum [Ruhr-Universität Bochum,](DE) studied a wild thale cress (Arabidopsis thaliana) population that colonized the base of an active stratovolcano. They found that a two-step molecular process rewired nutrient transport in the population. The findings, published today in the journal Science Advances, reveal an exceptionally clear case of an adaptive walk in a wild population. The discovery has broader implications for evolutionary biology and crop improvement.

Adapting to a novel soil environment

Nutrient homeostasis is crucial for proper plant growth and thus central to crop productivity. Pinpointing the genetic changes that allow plants to thrive in novel soil conditions provides insights into this important process. However, given the immense size of a genome, it is challenging to identify the specific functional variants that enable adaptation.

Members of the research team previously found that wild populations of the molecular model plant, Arabidopsis thaliana, commonly referred to as thale cress, colonized the Cape Verde Islands from North Africa and adapted using new mutations that arose after the colonization of the islands. Here, the scientists focus on the thale cress population from Fogo Island, which grows at the base of Pico de Fogo, an active stratovolcano. “We wanted to know: What does it take to live at the base of an active volcano? How did the plants adapt to the volcanic soil of Fogo?”, said Hancock.

“What we found was surprising,” said Emmanuel Tergemina, first author of the study. “While the plants from Fogo appeared to be healthy in their natural environment, they grew poorly on standard potting soil.” Chemical analysis of Fogo soils showed they were severely depauperate of manganese, an element that is crucial for energy production and proper plant growth. In contrast, leaves from Fogo plants grown on standard potting soil contained high levels of manganese, suggesting the plants had evolved a mechanism to increase manganese uptake.

Two evolutionary steps to a new adaptive peak

The scientists used a combination of genetic mapping and evolutionary analysis to discover the molecular steps that allowed the plants to colonize Fogo’s manganese-limited soil.

In a first evolutionary step, a mutation disrupted the primary iron transport gene (IRT1), eliminating its function. Disruption of this gene in a natural population was striking because this key gene exists intact in all other worldwide populations of the thale cress species – no such disruptions are found elsewhere. Further, the patterns of genetic variation in the IRT1 genomic region suggest that the disrupted version of IRT1 was important in adaptation. Evolutionary reconstruction shows that the mutation swept quickly to fixation across the entire Fogo population so that all Fogo thale cress plants now carry this mutation. Using gene-editing technology (CRISPR-Cas9), the researchers examined the functional effects of IRT1 disruption in Fogo and found that it increases leaf manganese accumulation, which could explain its role in adaptation. However, the loss of the IRT1 transporter came with a cost: it severely reduced leaf iron.

In a second evolutionary step, the metal transporter gene NRAMP1 was duplicated in multiple parallel events. These duplications spread rapidly so that now nearly all thale cress plants in Fogo carry multiple copies of NRAMP1 in their genomes. These duplications amplify NRAMP1 gene function, increasing iron transport and compensating for the iron deficiency induced by IRT1 disruption. Moreover, the amplification occurred by several independent duplication events across the island population. This was unexpected given the short time since colonization (around 5000 years) and the lack of similar events in other worldwide populations. “The rapid rise in frequency of these duplications together with their beneficial effect on nutrient homeostasis indicates these were important in adaptation”, explained Hancock. “Overall, our results provide an exceptionally clear example of how simple genetic changes can rewire nutrient processing in plants, enabling adaptation to a novel soil environment.”

Implications for crop improvement

These results also provide some encouraging news for crop breeding. Traditionally, information about gene function has come from studies of individual mutant lines. However, by using variation that exists in nature, it is possible to uncover more complex multi-step processes that can lead to changes in agriculturally-relevant traits. “The discovery that a simple two-step process alters nutrient transport in this case may offer clues for approaches to improve crops to better fit local soil environments. Moreover, gene disruption and gene amplification, as in the case of IRT1 and NRAMP1 in Fogo, are some of the simplest genetic changes to engineer, which makes them especially exciting because it means that they could be readily transferable to other species,” concluded Tergemina.

See the full article here.

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition

The MPG Institute for Plant Breeding Research was founded in Müncheberg, Germany in 1928 as part of the Kaiser-Wilhelm-Gesellschaft. The founding director, Erwin Baur, initiated breeding programmes with fruits and berries, and basic research on Antirrhinum majus and the domestication of lupins. After the Second World War, the institute moved west to Voldagsen, and was relocated to new buildings on the present site in Cologne in 1955.

The modern era of the Institute began in 1978 with the appointment of Jeff Schell and the development of plant transformation technologies and plant molecular genetics. The focus on molecular genetics was extended in 1980 with the appointment of Heinz Saedler. The appointment in 1983 of Klaus Hahlbrock broadened the expertise of the Institute in the area of plant biochemistry, and the arrival of Francesco Salamini in 1985 added a focus on crop genetics. During the period 1978-1990, the Institute was greatly expanded and new buildings were constructed for the departments led by Schell, Hahlbrock and Salamini, in addition to a new lecture hall and the Max Delbrück Laboratory building that housed independent research groups over a period of 10 years.

A new generation of directors was appointed from 2000 with the approaching retirements of Klaus Hahlbrock and Jeff Schell. Paul Schulze-Lefert and George Coupland were appointed in 2000 and 2001, respectively, and Maarten Koornneef arrived three years later upon the retirement of Francesco Salamini. The new scientific departments brought a strong focus on utilising model species to understand the regulatory principles and molecular mechanisms underlying selected traits. The longer-term aim is to translate these discoveries to breeding programmes through the development of rational breeding concepts. The arrival of a new generation of Directors also required modernization of the infrastructure. So far, this has involved complete refurbishment of the building that houses the Plant Developmental Biology laboratory (2004), construction of a new guesthouse and library (2005), planning of new buildings for the administration and technical workshops (2009), and a new laboratory building completed in May 2012. The new laboratory building includes a section that links the three scientific departments, offices and the Bioinformatics Research Group.

Departments

Department of Plant Developmental Biology
Department of Plant Microbe Interactions
Department of Comparative Development and Genetics
Department of Chromosome Biology

MPG Society for the Advancement of Science [MPG Gesellschaft zur Förderung der Wissenschaften e. V.] is a formally independent non-governmental and non-profit association of German research institutes founded in 1911 as the Kaiser Wilhelm Society and renamed the Max Planck Society in 1948 in honor of its former president, theoretical physicist Max Planck. The society is funded by the federal and state governments of Germany as well as other sources.

According to its primary goal, the MPG Society supports fundamental research in the natural, life and social sciences, the arts and humanities in its 83 (as of January 2014) MPG Institutes. The society has a total staff of approximately 17,000 permanent employees, including 5,470 scientists, plus around 4,600 non-tenured scientists and guests. Society budget for 2015 was about €1.7 billion.

The MPG Institutes focus on excellence in research. The MPG Society has a world-leading reputation as a science and technology research organization, with 33 Nobel Prizes awarded to their scientists, and is generally regarded as the foremost basic research organization in Europe and the world. In 2013, the Nature Publishing Index placed the MPG institutes fifth worldwide in terms of research published in Nature journals (after Harvard University, The Massachusetts Institute of Technology, Stanford University and The National Institutes of Health). In terms of total research volume (unweighted by citations or impact), the Max Planck Society is only outranked by The Chinese Academy of Sciences [中国科学院](CN), The Russian Academy of Sciences [Росси́йская акаде́мия нау́к](RU) and Harvard University. The Thomson Reuters-Science Watch website placed the MPG Society as the second leading research organization worldwide following Harvard University, in terms of the impact of the produced research over science fields.

The MPG Society and its predecessor Kaiser Wilhelm Society hosted several renowned scientists in their fields, including Otto Hahn, Werner Heisenberg, and Albert Einstein.

History

The organization was established in 1911 as the Kaiser Wilhelm Society, or Kaiser-Wilhelm-Gesellschaft (KWG), a non-governmental research organization named for the then German emperor. The KWG was one of the world’s leading research organizations; its board of directors included scientists like Walther Bothe, Peter Debye, Albert Einstein, and Fritz Haber. In 1946, Otto Hahn assumed the position of President of KWG, and in 1948, the society was renamed the Max Planck Society (MPG) after its former President (1930–37) Max Planck, who died in 1947.

The MPG Society has a world-leading reputation as a science and technology research organization. In 2006, the Times Higher Education Supplement rankings of non-university research institutions (based on international peer review by academics) placed the MPG Society as No.1 in the world for science research, and No.3 in technology research (behind AT&T Corporation and The DOE’s Argonne National Laboratory.

The domain mpg.de attracted at least 1.7 million visitors annually by 2008 according to a Compete.com study.

MPG Institutes and research groups

The MPG Society consists of over 80 research institutes. In addition, the society funds a number of Max Planck Research Groups (MPRG) and International Max Planck Research Schools (IMPRS). The purpose of establishing independent research groups at various universities is to strengthen the required networking between universities and institutes of the Max Planck Society.
The research units are primarily located across Europe with a few in South Korea and the U.S. In 2007, the Society established its first non-European centre, with an institute on the Jupiter campus of Florida Atlantic University (US) focusing on neuroscience.
The MPG Institutes operate independently from, though in close cooperation with, the universities, and focus on innovative research which does not fit into the university structure due to their interdisciplinary or transdisciplinary nature or which require resources that cannot be met by the state universities.

Internally, MPG Institutes are organized into research departments headed by directors such that each MPI has several directors, a position roughly comparable to anything from full professor to department head at a university. Other core members include Junior and Senior Research Fellows.

In addition, there are several associated institutes:

International Max Planck Research Schools

Together with the Association of Universities and other Education Institutions in Germany, the Max Planck Society established numerous International Max Planck Research Schools (IMPRS) to promote junior scientists:

• Cologne Graduate School of Ageing Research, Cologne
• International Max Planck Research School for Intelligent Systems, at the Max Planck Institute for Intelligent Systems located in Tübingen and Stuttgart
• International Max Planck Research School on Adapting Behavior in a Fundamentally Uncertain World (Uncertainty School), at the Max Planck Institutes for Economics, for Human Development, and/or Research on Collective Goods
• International Max Planck Research School for Analysis, Design and Optimization in Chemical and Biochemical Process Engineering, Magdeburg
• International Max Planck Research School for Astronomy and Cosmic Physics, Heidelberg at the MPI for Astronomy
• International Max Planck Research School for Astrophysics, Garching at the MPI for Astrophysics
• International Max Planck Research School for Complex Surfaces in Material Sciences, Berlin
• International Max Planck Research School for Computer Science, Saarbrücken
• International Max Planck Research School for Earth System Modeling, Hamburg
• International Max Planck Research School for Elementary Particle Physics, Munich, at the MPI for Physics
• International Max Planck Research School for Environmental, Cellular and Molecular Microbiology, Marburg at the Max Planck Institute for Terrestrial Microbiology
• International Max Planck Research School for Evolutionary Biology, Plön at the Max Planck Institute for Evolutionary Biology
• International Max Planck Research School “From Molecules to Organisms”, Tübingen at the Max Planck Institute for Developmental Biology
• International Max Planck Research School for Global Biogeochemical Cycles, Jena at the Max Planck Institute for Biogeochemistry
• International Max Planck Research School on Gravitational Wave Astronomy, Hannover and Potsdam MPI for Gravitational Physics
• International Max Planck Research School for Heart and Lung Research, Bad Nauheim at the Max Planck Institute for Heart and Lung Research
• International Max Planck Research School for Infectious Diseases and Immunity, Berlin at the Max Planck Institute for Infection Biology
• International Max Planck Research School for Language Sciences, Nijmegen
• International Max Planck Research School for Neurosciences, Göttingen
• International Max Planck Research School for Cognitive and Systems Neuroscience, Tübingen
• International Max Planck Research School for Marine Microbiology (MarMic), joint program of the Max Planck Institute for Marine Microbiology in Bremen, the University of Bremen, the Alfred Wegener Institute for Polar and Marine Research in Bremerhaven, and the Jacobs University Bremen
• International Max Planck Research School for Maritime Affairs, Hamburg
• International Max Planck Research School for Molecular and Cellular Biology, Freiburg
• International Max Planck Research School for Molecular and Cellular Life Sciences, Munich
• International Max Planck Research School for Molecular Biology, Göttingen
• International Max Planck Research School for Molecular Cell Biology and Bioengineering, Dresden
• International Max Planck Research School Molecular Biomedicine, program combined with the ‘Graduate Programm Cell Dynamics And Disease’ at the University of Münster and the Max Planck Institute for Molecular Biomedicine
• International Max Planck Research School on Multiscale Bio-Systems, Potsdam
• International Max Planck Research School for Organismal Biology, at the University of Konstanz and the Max Planck Institute for Ornithology
• International Max Planck Research School on Reactive Structure Analysis for Chemical Reactions (IMPRS RECHARGE), Mülheim an der Ruhr, at the Max Planck Institute for Chemical Energy Conversion
• International Max Planck Research School for Science and Technology of Nano-Systems, Halle at Max Planck Institute of Microstructure Physics
• International Max Planck Research School for Solar System Science at the University of Göttingen hosted by MPI for Solar System Research
• International Max Planck Research School for Astronomy and Astrophysics, Bonn, at the MPI for Radio Astronomy (formerly the International Max Planck Research School for Radio and Infrared Astronomy)
• International Max Planck Research School for the Social and Political Constitution of the Economy, Cologne
• International Max Planck Research School for Surface and Interface Engineering in Advanced Materials, Düsseldorf at Max Planck Institute for Iron Research GmbH
• International Max Planck Research School for Ultrafast Imaging and Structural Dynamics, Hamburg

Max Planck Schools

• Max Planck School of Cognition
• Max Planck School Matter to Life
• Max Planck School of Photonics

Max Planck Center

• The Max Planck Centre for Attosecond Science (MPC-AS), POSTECH Pohang
• The Max Planck POSTECH Center for Complex Phase Materials, POSTECH Pohang

Max Planck Institutes

Among others:
• Max Planck Institute for Neurobiology of Behavior – caesar, Bonn
• Max Planck Institute for Aeronomics in Katlenburg-Lindau was renamed to Max Planck Institute for Solar System Research in 2004;
• Max Planck Institute for Biology in Tübingen was closed in 2005;
• Max Planck Institute for Cell Biology in Ladenburg b. Heidelberg was closed in 2003;
• Max Planck Institute for Economics in Jena was renamed to the Max Planck Institute for the Science of Human History in 2014;
• Max Planck Institute for Ionospheric Research in Katlenburg-Lindau was renamed to Max Planck Institute for Aeronomics in 1958;
• Max Planck Institute for Metals Research, Stuttgart
• Max Planck Institute of Oceanic Biology in Wilhelmshaven was renamed to Max Planck Institute of Cell Biology in 1968 and moved to Ladenburg 1977;
• Max Planck Institute for Psychological Research in Munich merged into the Max Planck Institute for Human Cognitive and Brain Sciences in 2004;
• Max Planck Institute for Protein and Leather Research in Regensburg moved to Munich 1957 and was united with the Max Planck Institute for Biochemistry in 1977;
• Max Planck Institute for Virus Research in Tübingen was renamed as Max Planck Institute for Developmental Biology in 1985;
• Max Planck Institute for the Study of the Scientific-Technical World in Starnberg (from 1970 until 1981 (closed)) directed by Carl Friedrich von Weizsäcker and Jürgen Habermas.
• Max Planck Institute for Behavioral Physiology
• Max Planck Institute of Experimental Endocrinology
• Max Planck Institute for Foreign and International Social Law
• Max Planck Institute for Physics and Astrophysics
• Max Planck Research Unit for Enzymology of Protein Folding
• Max Planck Institute for Biology of Ageing

From Ludwig Maximilian University of Munich [Ludwig-Maximilians-Universität München] (DE) : “The origin of life- a paradigm shift”

From Ludwig Maximilian University of Munich [Ludwig-Maximilians-Universität München] (DE)

11 May 2022

According to a new concept by LMU chemists led by Thomas Carell it was a novel molecular species composed out of RNA and peptides that set in motion the evolution of life into more complex forms.

LMU-chemists Felix Müller (left) and Luis Escobar discussing a new prebiotic molecular design | © Markus Müller / LMU.

Investigating the question as to how life could emerge long ago on the early Earth is one of the most fascinating challenges for science. Which conditions must have prevailed for the basic building blocks of more complex life to form? One of the main answers is based upon the so-called RNA world idea, which molecular biology pioneer Walter Gilbert formulated in 1986. The hypothesis holds that nucleotides – the basic building blocks of the nucleic acids A, C, G, and U – emerged out of the primordial soup, and that short RNA molecules then formed out of the nucleotides. These so-called oligonucleotides were already capable of encoding small amounts of genetic information.

As such single-stranded RNA molecules could also combine into double strands, however, this gave rise to the theoretical possibility that the molecules could replicate themselves – i.e. reproduce. Only two nucleotides fit together in each case, meaning that one strand is the exact counterpart of another and thus forms the template for another strand.

In the course of evolution, this replication could have improved and at some stage yielded more complex life. “The RNA world idea has the big advantage that it sketches out a pathway whereby complex biomolecules such as nucleic acids with optimized catalytic and, at the same time, information-coding properties can emerge,” says LMU chemist Thomas Carell. Genetic material, as we understand it today, is made up of double strands of DNA, a slightly modified, durable form of macromolecule composed of nucleotides.

However, the hypothesis is not without its issues. For example, RNS is a very fragile molecule, especially when it gets longer. Furthermore, it is not clear how the linking of RNA molecules with the world of proteins could have come about, for which the genetic material, as we know, supplies the blueprints. As laid out in a new paper published in Nature, Carell’s working group has discovered a way in which this linking could have occurred.

Luis Escobar from the Carell Group in his laboratory. | © Markus Müller / LMU.

To understand, we must take another, closer look at RNA. In itself, RNA is a complicated macromolecule. In addition to the four canonical bases A, C, G, and U, which encode genetic information, it also contains non-canonical bases, some of which have very unusual structures. These non-information-coding nucleotides are very important for the functioning of RNA molecules. We currently have knowledge of more than 120 such modified RNA nucleosides, which nature incorporates into RNA molecules. It is highly probable that they are relicts of the former RNA world.

The Carell group has now discovered that these non-canonical nucleosides are the key ingredient, as it were, that allows the RNA world to link up with the world of proteins. Some of these molecular fossils can, when located in RNA, “adorn” themselves with individual amino acids or even small chains of them (peptides), according to Carell. This results in small chimeric RNA-peptide structures when amino acids or peptides happen to be present in a solution simultaneously alongside the RNA. In such structures, the amino acids and peptides linked to the RNA then even react with each other to form ever larger and more complex peptides. “In this way, we created RNA-peptide particles in the lab that could encode genetic information and even formed lengthening peptides,” says Carell.

The ancient fossil nucleosides are therefore somewhat akin to nuclei in RNA, forming a core upon which long peptide chains can grow. On some strands of RNA, the peptides were even growing at several points. “That was a very surprising discovery,” says Carell. “It’s possible that there never was a pure RNA world, but that RNA and peptides co-existed from the beginning in a common molecule.” As such, we should expand the concept of an RNA world to that of an RNA-peptide world. The peptides and the RNA mutually supported each other in their evolution, the new idea proposes.

According to the new theory, a decisive element at the beginning was the presence of RNA molecules that could adorn themselves with amino acids and peptides and so join them into larger peptide structures. “RNA developed slowly into a constantly improving amino acid linking catalyst,” says Carell. This relationship between RNA and peptides or proteins has remained to this day. The most important RNA catalyst is the ribosome, which still links amino acids into long peptide chains today. One of the most complicated RNA machines, it is responsible in every cell for translating genetic information into functional proteins. “The RNA-peptide world thus solves the chicken-and-egg problem,” says Carell. “The new idea creates a foundation upon which the origin of life gradually becomes explicable.”

See the full article here.

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition

Welcome to Ludwig Maximilian University of Munich [Ludwig-Maximilians-Universität München] (DE) – the University in the heart of Munich. LMU is recognized as one of Europe’s premier academic and research institutions. Since our founding in 1472, LMU has attracted inspired scholars and talented students from all over the world, keeping the University at the nexus of ideas that challenge and change our complex world.

Ludwig Maximilian University of Munich [Ludwig-Maximilians-Universität München] (DE) is a public research university located in Munich, Germany.

The University of Munich is Germany’s sixth-oldest university in continuous operation. Originally established in Ingolstadt in 1472 by Duke Ludwig IX of Bavaria-Landshut, the university was moved in 1800 to Landshut by King Maximilian I of Bavaria when Ingolstadt was threatened by the French, before being relocated to its present-day location in Munich in 1826 by King Ludwig I of Bavaria. In 1802, the university was officially named Ludwig-Maximilians-Universität by King Maximilian I of Bavaria in his as well as the university’s original founder’s honour.

The University of Munich is associated with 43 Nobel laureates (as of October 2020). Among these were Wilhelm Röntgen, Max Planck, Werner Heisenberg, Otto Hahn and Thomas Mann. Pope Benedict XVI was also a student and professor at the university. Among its notable alumni, faculty and researchers are inter alia Rudolf Peierls, Josef Mengele, Richard Strauss, Walter Benjamin, Joseph Campbell, Muhammad Iqbal, Marie Stopes, Wolfgang Pauli, Bertolt Brecht, Max Horkheimer, Karl Loewenstein, Carl Schmitt, Gustav Radbruch, Ernst Cassirer, Ernst Bloch, Konrad Adenauer. The LMU has recently been conferred the title of “University of Excellence” under the German Universities Excellence Initiative.

LMU is currently the second-largest university in Germany in terms of student population; in the winter semester of 2018/2019, the university had a total of 51,606 matriculated students. Of these, 9,424 were freshmen while international students totalled 8,875 or approximately 17% of the student population. As for operating budget, the university records in 2018 a total of 734,9 million euros in funding without the university hospital; with the university hospital, the university has a total funding amounting to approximately 1.94 billion euros.

Faculties

LMU’s Institute of Systematic Botany is located at Botanischer Garten München-Nymphenburg
Faculty of chemistry buildings at the Martinsried campus of LMU Munich

The university consists of 18 faculties which oversee various departments and institutes. The official numbering of the faculties and the missing numbers 06 and 14 are the result of breakups and mergers of faculties in the past. The Faculty of Forestry Operations with number 06 has been integrated into the Technical University of Munich [Technische Universität München] (DE) in 1999 and faculty number 14 has been merged with faculty number 13.

01 Faculty of Catholic Theology
02 Faculty of Protestant Theology
03 Faculty of Law
04 Faculty of Business Administration
05 Faculty of Economics
07 Faculty of Medicine
08 Faculty of Veterinary Medicine
09 Faculty for History and the Arts
10 Faculty of Philosophy, Philosophy of Science and Study of Religion
11 Faculty of Psychology and Educational Sciences
12 Faculty for the Study of Culture
13 Faculty for Languages and Literatures
15 Faculty of Social Sciences
16 Faculty of Mathematics, Computer Science and Statistics
17 Faculty of Physics
18 Faculty of Chemistry and Pharmacy
19 Faculty of Biology
20 Faculty of Geosciences and Environmental Sciences

Research centres

In addition to its 18 faculties, the University of Munich also maintains numerous research centres involved in numerous cross-faculty and transdisciplinary projects to complement its various academic programmes. Some of these research centres were a result of cooperation between the university and renowned external partners from academia and industry; the Rachel Carson Center for Environment and Society, for example, was established through a joint initiative between LMU Munich and the Deutsches Museum, while the Parmenides Center for the Study of Thinking resulted from the collaboration between the Parmenides Foundation and LMU Munich’s Human Science Center.

Some of the research centres which have been established include:

Center for Integrated Protein Science Munich (CIPSM)
Graduate School of Systemic Neurosciences (GSN)
Helmholtz Zentrum München – German Research Center for Environmental Health
Nanosystems Initiative Munich (NIM)
Parmenides Center for the Study of Thinking
Rachel Carson Center for Environment and Society

From The University of California-Berkeley: “Now fully complete human genome reveals new secrets”

From The University of California-Berkeley

March 31, 2022 [Just found this, missed the first time around.]
Robert Sanders
rlsanders@berkeley.edu

Sequencing the last 8% of the human genome has taken 20 years and the invention of new techniques for reading long sequences of the genetic code, which consists of the nucleotides C, T, G and A. The entire genome consists of more than 3 billion nucleotides. Image courtesy of Ernesto del Aguila III, National Human Genome Research Institute, The National Institutes of Health.

When scientists announced the complete sequence of the human genome in 2003 they were fudging a bit.

In fact, nearly 20 years later, about 8% of the genome has never been fully sequenced, largely because it consists of highly repetitive chunks of DNA that are hard to align with the rest.

But a three-year-old consortium has finally filled in that remaining DNA, providing the first complete, gapless genome sequence for scientists and physicians to refer to.

The newly completed genome dubbed T2T-CHM13, represents a major upgrade from the current reference genome, called GRCh38, which is used by doctors when searching for mutations linked to disease, as well as by scientists looking at the evolution of human genetic variation.

Among other things, the new DNA sequences reveal never-before-seen detail about the region around the centromere, which is where chromosomes are grabbed and pulled apart when cells divide, ensuring that each “daughter” cell inherits the correct number of chromosomes. Variability within this region may also provide new evidence of how our human ancestors evolved in Africa.

“Uncovering the complete sequence of these formerly missing regions of the genome told us so much about how they’re organized, which was totally unknown for many chromosomes,” said Nicolas Altemose, a postdoctoral fellow at the University of California-Berkeley, and a co-author of four new papers about the completed genome. “Before, we just had the blurriest picture of what was there, and now it’s crystal clear down to single base pair resolution.”

Altemose is first author of one paper that describes the base pair sequences around the centromere. A paper explaining how the sequencing was done appeared in the April 1 print edition of the journal Science, while Altemose’s centromere paper and four others describing what the new sequences tell us are summarized in the journal with the full papers posted online. Four companion papers, including one for which Altemose is co-first author, also appeared online April 1 in the journal Nature Methods.

The sequencing and analysis were performed by a team of more than 100 people, the so-called Telemere-to-Telomere Consortium, or T2T, named for the telomeres that cap the ends of all chromosomes. The consortium’s gapless version of all 22 autosomes and the X sex chromosome is composed of 3.055 billion base pairs, the units from which chromosomes and our genes are built, and 19,969 protein-coding genes. Of the protein-coding genes, the T2T team found about 2,000 new ones, most of them disabled, but 115 of which may still be expressed. They also found about 2 million additional variants in the human genome, 622 of which occur in medically relevant genes.

“In the future, when someone has their genome sequenced, we will be able to identify all of the variants in their DNA and use that information to better guide their health care,” said Adam Phillippy, one of the leaders of T2T and a senior investigator at The National Human Genome Research Institute of The National Institutes of Health. “Truly finishing the human genome sequence was like putting on a new pair of glasses. Now that we can clearly see everything, we are one step closer to understanding what it all means.”

The evolving centromere

The new DNA sequences in and around the centromere total about 6.2% of the entire genome, or nearly 190 million base pairs, or nucleotides. Of the remaining newly added sequences, most are found around the telomeres at the end of each chromosome and in the regions surrounding ribosomal genes. The entire genome is made of just four types of nucleotides, which, in groups of three, code for the amino acids used to build proteins. Altemose’s main research involves finding and exploring areas of the chromosomes where proteins interact with DNA.

The spindles (green) that pull chromosomes apart during cell division are attached to a protein complex called the kinetochore, which latches onto the chromosome at a place called the centromere — a region containing highly repetitive DNA sequences. Comparing the sequences of these repeats revealed where mutations have accumulated over millions of years, reflecting the relative age of each repeat. Repeats in the active centromere tend to be the youngest and most recently duplicated sequences in the region, and they have strikingly low DNA methylation. Surrounding the active centromere on both sides are older repeats, probably the relics of former centromeres, with the oldest ones farthest from the active centromere. The researchers hope that new experimental methods will help reveal why centromeres evolve from the middle, as well as why this pattern is so closely associated with binding by the kinetochore and with low DNA methylation. Image courtesy of Nicolas Altemose/UC Berkeley.

“Without proteins, DNA is nothing,” said Altemose, who earned a Ph.D. in bioengineering jointly from UC Berkeley and The University of California-San Francisco in 2021 after having received a D.Phil. in statistics from The University of Oxford (UK). “DNA is a set of instructions with no one to read it if it doesn’t have proteins around to organize it, regulate it, repair it when it’s damaged and replicate it. Protein-DNA interactions are really where all the action is happening for genome regulation, and being able to map where certain proteins bind to the genome is really important for understanding their function.”

After the T2T consortium sequenced the missing DNA, Altemose and his team used new techniques to find the place within the centromere where a big protein complex called the kinetochore solidly grips the chromosome so that other machines inside the nucleus can pull chromosome pairs apart.

“When this goes wrong, you end up with missegregated chromosomes, and that leads to all kinds of problems,” he said. “If that happens in meiosis, that means you can have chromosomal anomalies leading to spontaneous miscarriage or congenital diseases. If it happens in somatic cells, you can end up with cancer — basically, cells that have massive misregulation.”

What they found in and around the centromeres were layers of new sequences overlaying layers of older sequences, as if through evolution new centromere regions have been laid down repeatedly to bind to the kinetochore. The older regions are characterized by more random mutations and deletions, indicating they’re no longer used by the cell. The newer sequences where the kinetochore binds are much less variable, and also less methylated. The addition of a methyl group is an epigenetic tag that tends to silence genes.

All of the layers in and around the centromere are composed of repetitive lengths of DNA, based on a unit about 171 base pairs long, which is roughly the length of DNA that wraps around a group of proteins to form a nucleosome, keeping the DNA packaged and compact. These 171 base pair units form even larger repeat structures that are duplicated many times in tandem, building up a large region of repetitive sequences around the centromere.

The T2T team focused on only one human genome, obtained from a non-cancerous tumor called a hydatidiform mole, which is essentially a human embryo that rejected the maternal DNA and duplicated its paternal DNA instead. Such embryos die and transform into tumors. But the fact that this mole had two identical copies of the paternal DNA — both with the father’s X chromosome, instead of different DNA from both mother and father — made it easier to sequence.

The researchers also released this week the complete sequence of a Y chromosome from a different source, which took nearly as long to assemble as the rest of the genome combined, Altemose said. The analysis of this new Y chromosome sequence will appear in a future publication.

Altemose and his team, which included UC Berkeley project scientist Sasha Langley, also used the new reference genome as a scaffold to compare the centromeric DNA of 1,600 individuals from around the world, revealing major differences in both the sequence and copy number of repetitive DNA around the centromere. Previous studies have shown that when groups of ancient humans migrated out of Africa to the rest of the world, they took only a small sample of genetic variants with them. Altemose and his team confirmed that this pattern extends into centromeres.

“What we found is that in individuals with recent ancestry outside the African continent, their centromeres, at least on chromosome X, tend to fall into two big clusters, while most of the interesting variation is in individuals who have recent African ancestry,” Altemose said. “This isn’t entirely a surprise, given what we know about the rest of the genome. But what it suggests is that if we want to look at the interesting variation in these centromeric regions, we really need to have a focused effort to sequence more African genomes and do complete telomere-to-telomere sequence assembly.”

DNA sequences around the centromere could also be used to trace human lineages back to our common ape ancestors, he noted.

“As you move away from the site of the active centromere, you get more and more degraded sequence, to the point where if you go out to the furthest shores of this sea of repetitive sequences, you start to see the ancient centromere that, perhaps, our distant primate ancestors used to bind to the kinetochore,” Altemose said. “It’s almost like layers of fossils.”

Long-read sequencing a game changer

The T2T’s success is due to improved techniques for sequencing long stretches of DNA at once, which helps when determining the order of highly repetitive stretches of DNA. Among these are PacBio’s HiFi sequencing, which can read lengths of more than 20,000 base pairs with high accuracy. Technology developed by Oxford Nanopore Technologies Ltd., on the other hand, can read up to several million base pairs in sequence, though with less fidelity. For comparison, so-called next-generation sequencing by Illumina Inc. is limited to hundreds of base pairs.

“These new long-read DNA sequencing technologies are just incredible; they’re such game changers, not only for this repetitive DNA world, but because they allow you to sequence single long molecules of DNA,” Altemose said. “You can begin to ask questions at a level of resolution that just wasn’t possible before, not even with short-read sequencing methods.”

Altemose plans to explore the centromeric regions further, using an improved technique he and colleagues at Stanford developed to pinpoint the sites on the chromosome that are bound by proteins, similar to how the kinetochore binds to the centromere. This technique, too, uses long-read sequencing technology. He and his group described the technique, called Directed Methylation with Long-read sequencing (DiMeLo-seq), in a paper that appeared this week in the journal Nature Methods.

Meanwhile, the T2T consortium is partnering with the Human PanGenome Reference Consortium to work toward a reference genome that represents all of humanity.

“Instead of just having one reference from one human individual or one hydatidiform mole, which isn’t even a real human individual, we should have a reference that represents everybody,” Altemose said. “There are various ideas about how to accomplish that. But what we need first is a grasp of what that variation looks like, and we need lots of high-quality individual genome sequences to accomplish that.”

His work on the centromeric regions, which he called “a passion project,” was funded by postdoctoral fellowships. The leaders of the T2T project were Karen Miga of The University of California-Santa Cruz, Evan Eichler of The University of Washington, and Adam Phillippy of NHGRI, which provided much of the funding. Other UC Berkeley co-authors of the centromere paper are Aaron Streets, assistant professor of bioengineering; Abby Dernburg and Gary Karpen, professors of molecular and cell biology; project scientist Sasha Langley; and former postdoctoral fellow Gina Caldas.

See the full article here .

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition

The The University of California-Berkeley is a public land-grant research university in Berkeley, California. Established in 1868 as the state’s first land-grant university, it was the first campus of the University of California system and a founding member of the Association of American Universities . Its 14 colleges and schools offer over 350 degree programs and enroll some 31,000 undergraduate and 12,000 graduate students. Berkeley is ranked among the world’s top universities by major educational publications.

Berkeley hosts many leading research institutes, including the Mathematical Sciences Research Institute and the Space Sciences Laboratory. It founded and maintains close relationships with three national laboratories at DOE’s Lawrence Berkeley National Laboratory, DOE’s Lawrence Livermore National Laboratory and DOE’s Los Alamos National Lab, and has played a prominent role in many scientific advances, from the Manhattan Project and the discovery of 16 chemical elements to breakthroughs in computer science and genomics. Berkeley is also known for student activism and the Free Speech Movement of the 1960s.

Berkeley alumni and faculty count among their ranks 110 Nobel laureates (34 alumni), 25 Turing Award winners (11 alumni), 14 Fields Medalists, 28 Wolf Prize winners, 103 MacArthur “Genius Grant” recipients, 30 Pulitzer Prize winners, and 19 Academy Award winners. The university has produced seven heads of state or government; five chief justices, including Chief Justice of the United States Earl Warren; 21 cabinet-level officials; 11 governors; and 25 living billionaires. It is also a leading producer of Fulbright Scholars, MacArthur Fellows, and Marshall Scholars. Berkeley alumni, widely recognized for their entrepreneurship, have founded many notable companies.

Berkeley’s athletic teams compete in Division I of the NCAA, primarily in the Pac-12 Conference, and are collectively known as the California Golden Bears. The university’s teams have won 107 national championships, and its students and alumni have won 207 Olympic medals.

Made possible by President Lincoln’s signing of the Morrill Act in 1862, the University of California was founded in 1868 as the state’s first land-grant university by inheriting certain assets and objectives of the private College of California and the public Agricultural, Mining, and Mechanical Arts College. Although this process is often incorrectly mistaken for a merger, the Organic Act created a “completely new institution” and did not actually merge the two precursor entities into the new university. The Organic Act states that the “University shall have for its design, to provide instruction and thorough and complete education in all departments of science, literature and art, industrial and professional pursuits, and general education, and also special courses of instruction in preparation for the professions”.

Ten faculty members and 40 students made up the fledgling university when it opened in Oakland in 1869. Frederick H. Billings, a trustee of the College of California, suggested that a new campus site north of Oakland be named in honor of Anglo-Irish philosopher George Berkeley. The university began admitting women the following year. In 1870, Henry Durant, founder of the College of California, became its first president. With the completion of North and South Halls in 1873, the university relocated to its Berkeley location with 167 male and 22 female students.

Beginning in 1891, Phoebe Apperson Hearst made several large gifts to Berkeley, funding a number of programs and new buildings and sponsoring, in 1898, an international competition in Antwerp, Belgium, where French architect Émile Bénard submitted the winning design for a campus master plan.

20th century

In 1905, the University Farm was established near Sacramento, ultimately becoming the University of California-Davis. In 1919, Los Angeles State Normal School became the southern branch of the University, which ultimately became the University of California-Los Angeles. By 1920s, the number of campus buildings had grown substantially and included twenty structures designed by architect John Galen Howard.

In 1917, one of the nation’s first ROTC programs was established at Berkeley and its School of Military Aeronautics began training pilots, including Gen. Jimmy Doolittle. Berkeley ROTC alumni include former Secretary of Defense Robert McNamara and Army Chief of Staff Frederick C. Weyand as well as 16 other generals. In 1926, future fleet admiral Chester W. Nimitz established the first Naval ROTC unit at Berkeley.

In the 1930s, Ernest Lawrence helped establish the Radiation Laboratory (now DOE’s Lawrence Berkeley National Laboratory (US)) and invented the cyclotron, which won him the Nobel physics prize in 1939. Using the cyclotron, Berkeley professors and Berkeley Lab researchers went on to discover 16 chemical elements—more than any other university in the world. In particular, during World War II and following Glenn Seaborg’s then-secret discovery of plutonium, Ernest Orlando Lawrence’s Radiation Laboratory began to contract with the U.S. Army to develop the atomic bomb. Physics professor J. Robert Oppenheimer was named scientific head of the Manhattan Project in 1942. Along with the Lawrence Berkeley National Laboratory, Berkeley founded and was then a partner in managing two other labs, Los Alamos National Laboratory (1943) and Lawrence Livermore National Laboratory (1952).

By 1942, the American Council on Education ranked Berkeley second only to Harvard University in the number of distinguished departments.

In 1952, the University of California reorganized itself into a system of semi-autonomous campuses, with each campus given its own chancellor, and Clark Kerr became Berkeley’s first Chancellor, while Sproul remained in place as the President of the University of California.

Berkeley gained a worldwide reputation for political activism in the 1960s. In 1964, the Free Speech Movement organized student resistance to the university’s restrictions on political activities on campus—most conspicuously, student activities related to the Civil Rights Movement. The arrest in Sproul Plaza of Jack Weinberg, a recent Berkeley alumnus and chair of Campus CORE, in October 1964, prompted a series of student-led acts of formal remonstrance and civil disobedience that ultimately gave rise to the Free Speech Movement, which movement would prevail and serve as precedent for student opposition to America’s involvement in the Vietnam War.

In 1982, the Mathematical Sciences Research Institute (MSRI) was established on campus with support from the National Science Foundation and at the request of three Berkeley mathematicians — Shiing-Shen Chern, Calvin Moore and Isadore M. Singer. The institute is now widely regarded as a leading center for collaborative mathematical research, drawing thousands of visiting researchers from around the world each year.

21st century

In the current century, Berkeley has become less politically active and more focused on entrepreneurship and fundraising, especially for STEM disciplines.

Modern Berkeley students are less politically radical, with a greater percentage of moderates and conservatives than in the 1960s and 70s. Democrats outnumber Republicans on the faculty by a ratio of 9:1. On the whole, Democrats outnumber Republicans on American university campuses by a ratio of 10:1.

In 2007, the Energy Biosciences Institute was established with funding from BP and Stanley Hall, a research facility and headquarters for the California Institute for Quantitative Biosciences, opened. The next few years saw the dedication of the Center for Biomedical and Health Sciences, funded by a lead gift from billionaire Li Ka-shing; the opening of Sutardja Dai Hall, home of the Center for Information Technology Research in the Interest of Society; and the unveiling of Blum Hall, housing the Blum Center for Developing Economies. Supported by a grant from alumnus James Simons, the Simons Institute for the Theory of Computing was established in 2012. In 2014, Berkeley and its sister campus, University of California-San Fransisco, established the Innovative Genomics Institute, and, in 2020, an anonymous donor pledged $252 million to help fund a new center for computing and data science.

Since 2000, Berkeley alumni and faculty have received 40 Nobel Prizes, behind only Harvard and Massachusetts Institute of Technology among US universities; five Turing Awards, behind only MIT and Stanford University; and five Fields Medals, second only to Princeton University (US). According to PitchBook, Berkeley ranks second, just behind Stanford University, in producing VC-backed entrepreneurs.

From Penn Today: “With plants as a model studying the ‘complexity and reproducibility’ of Developmental Biology”

From Penn Today

at

University of Pennsylvania

May 6, 2022
Katherine Unger Baillie
Eric Sucar – Photographer

In his first year at Penn, biologist Aman Husbands is busy working on projects aimed at illuminating the molecular mechanisms that govern plant development.

By studying how plants develop, Aman Husbands, who joined the Department of Biology faculty this year, may make insights that find application well beyond the plant kingdom.

Nearly paper-thin, often with a complex two-dimensional shape, leaves may number into the hundreds of thousands on an organism like a white oak. Yet typically, each leaf appears quite similar in form.

How is it that a plant coordinates the production of these leaves, one after another, so carefully and so reproducibly?

The molecular forces governing this aspect of plant development are a focus of Aman Husbands, who joined Penn’s Biology Department faculty in the School of Arts & Sciences in January. Exploring proteins and protein families involved in different facets of plant growth, Husbands has identified key regulators that appear fundamental to biology, and not just plant biology.

His curiosity-driven research is not only illuminating the basic mechanisms responsible for why plants grow as they do but also has the potential to impact how plants stay resilient in the face of climate change. It may even shed light on aspects of development and disease in other species, humans included.

“You could break down the lab into complexity and reproducibility,” says Husbands, the Mitchell J. Blutt and Margo Krody Blutt Presidential Assistant Professor of Biology. “How do you create these beautiful, complex shapes? Biology should go wrong all the time, and yet it doesn’t. We’re interested in the mechanisms responsible.”

Drawn to plants

As a kid, Husbands, who grew up in Toronto, “wanted to be a marine biologist, like everyone,” he says. Around his second year at The University of Toronto (CA), when he began taking more specialized science courses, another aspect of biology caught his attention.

“Plants, for some reason, I loved,” he says. “It was a system that I just intuitively understood.”

Plant leaves begin to form as a small bump and then flatten into a complex, two-dimensional shape. Some of the research Husbands pursues examines how plants consistently form “these paper-thin structures over and over again,” rarely getting it wrong.

During his undergraduate years he worked with Nancy Dengler, whose lab group studies plant anatomy. Anatomy was also the focus of the lab he joined for his graduate work at The University of California-Riverside. But after a half a year he switched to join the lab of Patricia Springer, who “was asking really interesting questions about plant development, including how plants establish boundaries between their organs,” says Husbands. Springer gave him the freedom to explore the molecular aspects of plant development, and he began to ask questions about protein function.

His doctoral research focused on a family known as the LOB DOMAIN (LBD) genes, transcription factors that control how and when genes are turned on and off. “People assumed these were transcription factors but that had not been formally shown,” he says. Under the guidance of Harley Smith, another Riverside faculty member at the time, Husbands gained the molecular biology skillset to pursue those questions, identifying the binding site recognized by this protein family, which are specific to plants. “I’m still proud of that paper,” he says.

Moving back to the East Coast for his postdoctoral work, he joined the lab of Marja Timmermans at Cold Spring Harbor Laboratory in New York. With Timmermans, now at Eberhard Karl University of Tübingen [Eberhard Karls Universität Tübingen[(DE), Husbands began delving into a transcription factor complex that still makes up “the bread and butter” of his research today, known as the HD-ZIPIIIs. “What interested me about this family is that it’s very, very deeply conserved,” he says, its origins tracing back 750 million years or more in evolutionary time. HD-ZIPIII genes, if manipulated, impact multiple aspects of plant development, Husbands says, including stem cells, the plant vein system, and leaf architecture.

When leaf formation goes wrong

As Husbands moved from Cold Spring Harbor to a faculty position at Ohio State University, where he ran a lab for four years, and now to Penn, a question driving his work is, How can plants reliably churn out leaves that look the way they’re supposed to look? Plant biologists’ term for this is reproducibility or robustness, and Husbands studies it in the context of flat-leaf architecture, or the tendency of plants to consistently form “these paper-thin structures over and over again,” he says. “What makes this more compelling is that leaves don’t start out flat.” When they initially develop, they are ball-shaped, and only later flatten out into what most would recognize as a leaf: a thin form with a distinctive two-dimensional shape.

“It’s a very difficult process,” says Husbands. Plants usually get this right, but leaf growth occasionally goes awry. “You might get leaves curling up or down, which will lead to impacts on fitness,” he says.

Typically, however, Husbands says, “leaves always know, ‘This is my top; this is my bottom. I have a boundary from which to grow.’”

The concept of boundaries driving growth is not unique to plants but one that’s present in almost every developing organism. Thus, insights Husbands draws out in plants may have applications to other groups as well. “It’s a very classical developmental paradigm,” he says.

Other projects of Husbands involve collaborations with computational biologists and mathematicians. In one, he and colleagues are hoping to look for patterns in gene expression data in the hopes that new gene candidates will emerge as being central to the reproducibility and robustness of flat-leaf architecture.

Applications, partnerships, and inspiration

While Husbands is motivated by a love of basic science and discovery, he’s also moving his work into directions that might one day find real-world application. On the plant front, he notes that “engineering robustness,” by intervening with some of the transcription factors he’s studying, could enable plants to withstand the ups and downs of climate change. “We’re a ways away from that, but, if you could find a particular system that is susceptible to climate change, you could use these properties to basically shore it up, stabilize that biology and enable the plant to be resilient in the face of climate extremes.”

Going beyond plants, Husbands and his trainees are also investigating how the lipid binding domains they’ve studied in plants operate in proteins present across the tree of life, including a tumor suppressor protein present in humans. “We want to take knowledge from our work and others to develop strategies to affect activity of this tumor suppressor via this lipid-binding domain,” he says. “The therapeutic applications are obvious. If you develop a ligand to affect the activity of a tumor suppressor, you’re in business.”

With a department strong in plant biology as well as many other facets of science, and additional potential collaborators a stone’s throw away on campus, Husbands jumped at the opportunity to come to the Penn. “Penn is Penn,” he says. “During the recruitment process, just reading about what everyone was doing and their science—it’s just a firehose. You come away and you’re inspired.”

See the full article here .

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition

Academic life at University of Pennsylvania is unparalleled, with 100 countries and every U.S. state represented in one of the Ivy League’s most diverse student bodies. Consistently ranked among the top 10 universities in the country, Penn enrolls 10,000 undergraduate students and welcomes an additional 10,000 students to our world-renowned graduate and professional schools.

Penn’s award-winning educators and scholars encourage students to pursue inquiry and discovery, follow their passions, and address the world’s most challenging problems through an interdisciplinary approach.

The University of Pennsylvania is a private Ivy League research university in Philadelphia, Pennsylvania. The university claims a founding date of 1740 and is one of the nine colonial colleges chartered prior to the U.S. Declaration of Independence. Benjamin Franklin, Penn’s founder and first president, advocated an educational program that trained leaders in commerce, government, and public service, similar to a modern liberal arts curriculum.

Penn has four undergraduate schools as well as twelve graduate and professional schools. Schools enrolling undergraduates include the College of Arts and Sciences; the School of Engineering and Applied Science; the Wharton School; and the School of Nursing. Penn’s “One University Policy” allows students to enroll in classes in any of Penn’s twelve schools. Among its highly ranked graduate and professional schools are a law school whose first professor wrote the first draft of the United States Constitution, the first school of medicine in North America (Perelman School of Medicine, 1765), and the first collegiate business school (Wharton School, 1881).

Penn is also home to the first “student union” building and organization (Houston Hall, 1896), the first Catholic student club in North America (Newman Center, 1893), the first double-decker college football stadium (Franklin Field, 1924 when second deck was constructed), and Morris Arboretum, the official arboretum of the Commonwealth of Pennsylvania. The first general-purpose electronic computer (ENIAC) was developed at Penn and formally dedicated in 1946. In 2019, the university had an endowment of $14.65 billion, the sixth-largest endowment of all universities in the United States, as well as a research budget of $1.02 billion. The university’s athletics program, the Quakers, fields varsity teams in 33 sports as a member of the NCAA Division I Ivy League conference.

As of 2018, distinguished alumni and/or Trustees include three U.S. Supreme Court justices; 32 U.S. senators; 46 U.S. governors; 163 members of the U.S. House of Representatives; eight signers of the Declaration of Independence and seven signers of the U.S. Constitution (four of whom signed both representing two-thirds of the six people who signed both); 24 members of the Continental Congress; 14 foreign heads of state and two presidents of the United States, including Donald Trump. As of October 2019, 36 Nobel laureates; 80 members of the American Academy of Arts and Sciences; 64 billionaires; 29 Rhodes Scholars; 15 Marshall Scholars and 16 Pulitzer Prize winners have been affiliated with the university.

History

The University of Pennsylvania considers itself the fourth-oldest institution of higher education in the United States, though this is contested by Princeton University and Columbia University. The university also considers itself as the first university in the United States with both undergraduate and graduate studies.

In 1740, a group of Philadelphians joined together to erect a great preaching hall for the traveling evangelist George Whitefield, who toured the American colonies delivering open-air sermons. The building was designed and built by Edmund Woolley and was the largest building in the city at the time, drawing thousands of people the first time it was preached in. It was initially planned to serve as a charity school as well, but a lack of funds forced plans for the chapel and school to be suspended. According to Franklin’s autobiography, it was in 1743 when he first had the idea to establish an academy, “thinking the Rev. Richard Peters a fit person to superintend such an institution”. However, Peters declined a casual inquiry from Franklin and nothing further was done for another six years. In the fall of 1749, now more eager to create a school to educate future generations, Benjamin Franklin circulated a pamphlet titled Proposals Relating to the Education of Youth in Pensilvania, his vision for what he called a “Public Academy of Philadelphia”. Unlike the other colonial colleges that existed in 1749—Harvard University, William & Mary, Yale Unversity, and The College of New Jersey—Franklin’s new school would not focus merely on education for the clergy. He advocated an innovative concept of higher education, one which would teach both the ornamental knowledge of the arts and the practical skills necessary for making a living and doing public service. The proposed program of study could have become the nation’s first modern liberal arts curriculum, although it was never implemented because Anglican priest William Smith (1727-1803), who became the first provost, and other trustees strongly preferred the traditional curriculum.

Franklin assembled a board of trustees from among the leading citizens of Philadelphia, the first such non-sectarian board in America. At the first meeting of the 24 members of the board of trustees on November 13, 1749, the issue of where to locate the school was a prime concern. Although a lot across Sixth Street from the old Pennsylvania State House (later renamed and famously known since 1776 as “Independence Hall”), was offered without cost by James Logan, its owner, the trustees realized that the building erected in 1740, which was still vacant, would be an even better site. The original sponsors of the dormant building still owed considerable construction debts and asked Franklin’s group to assume their debts and, accordingly, their inactive trusts. On February 1, 1750, the new board took over the building and trusts of the old board. On August 13, 1751, the “Academy of Philadelphia”, using the great hall at 4th and Arch Streets, took in its first secondary students. A charity school also was chartered on July 13, 1753 by the intentions of the original “New Building” donors, although it lasted only a few years. On June 16, 1755, the “College of Philadelphia” was chartered, paving the way for the addition of undergraduate instruction. All three schools shared the same board of trustees and were considered to be part of the same institution. The first commencement exercises were held on May 17, 1757.

The institution of higher learning was known as the College of Philadelphia from 1755 to 1779. In 1779, not trusting then-provost the Reverend William Smith’s “Loyalist” tendencies, the revolutionary State Legislature created a University of the State of Pennsylvania. The result was a schism, with Smith continuing to operate an attenuated version of the College of Philadelphia. In 1791, the legislature issued a new charter, merging the two institutions into a new University of Pennsylvania with twelve men from each institution on the new board of trustees.

Penn has three claims to being the first university in the United States, according to university archives director Mark Frazier Lloyd: the 1765 founding of the first medical school in America made Penn the first institution to offer both “undergraduate” and professional education; the 1779 charter made it the first American institution of higher learning to take the name of “University”; and existing colleges were established as seminaries (although, as detailed earlier, Penn adopted a traditional seminary curriculum as well).

After being located in downtown Philadelphia for more than a century, the campus was moved across the Schuylkill River to property purchased from the Blockley Almshouse in West Philadelphia in 1872, where it has since remained in an area now known as University City. Although Penn began operating as an academy or secondary school in 1751 and obtained its collegiate charter in 1755, it initially designated 1750 as its founding date; this is the year that appears on the first iteration of the university seal. Sometime later in its early history, Penn began to consider 1749 as its founding date and this year was referenced for over a century, including at the centennial celebration in 1849. In 1899, the board of trustees voted to adjust the founding date earlier again, this time to 1740, the date of “the creation of the earliest of the many educational trusts the University has taken upon itself”. The board of trustees voted in response to a three-year campaign by Penn’s General Alumni Society to retroactively revise the university’s founding date to appear older than Princeton University, which had been chartered in 1746.

Research, innovations and discoveries

Penn is classified as an “R1” doctoral university: “Highest research activity.” Its economic impact on the Commonwealth of Pennsylvania for 2015 amounted to $14.3 billion. Penn’s research expenditures in the 2018 fiscal year were $1.442 billion, the fourth largest in the U.S. In fiscal year 2019 Penn received $582.3 million in funding from the National Institutes of Health.

In line with its well-known interdisciplinary tradition, Penn’s research centers often span two or more disciplines. In the 2010–2011 academic year alone, five interdisciplinary research centers were created or substantially expanded; these include the Center for Health-care Financing; the Center for Global Women’s Health at the Nursing School; the $13 million Morris Arboretum’s Horticulture Center; the $15 million Jay H. Baker Retailing Center at Wharton; and the $13 million Translational Research Center at Penn Medicine. With these additions, Penn now counts 165 research centers hosting a research community of over 4,300 faculty and over 1,100 postdoctoral fellows, 5,500 academic support staff and graduate student trainees. To further assist the advancement of interdisciplinary research President Amy Gutmann established the “Penn Integrates Knowledge” title awarded to selected Penn professors “whose research and teaching exemplify the integration of knowledge”. These professors hold endowed professorships and joint appointments between Penn’s schools.

Penn is also among the most prolific producers of doctoral students. With 487 PhDs awarded in 2009, Penn ranks third in the Ivy League, only behind Columbia University and Cornell University (Harvard University did not report data). It also has one of the highest numbers of post-doctoral appointees (933 in number for 2004–2007), ranking third in the Ivy League (behind Harvard and Yale University) and tenth nationally.

In most disciplines Penn professors’ productivity is among the highest in the nation and first in the fields of epidemiology, business, communication studies, comparative literature, languages, information science, criminal justice and criminology, social sciences and sociology. According to the National Research Council nearly three-quarters of Penn’s 41 assessed programs were placed in ranges including the top 10 rankings in their fields, with more than half of these in ranges including the top five rankings in these fields.

Penn’s research tradition has historically been complemented by innovations that shaped higher education. In addition to establishing the first medical school; the first university teaching hospital; the first business school; and the first student union Penn was also the cradle of other significant developments. In 1852, Penn Law was the first law school in the nation to publish a law journal still in existence (then called The American Law Register, now the Penn Law Review, one of the most cited law journals in the world). Under the deanship of William Draper Lewis, the law school was also one of the first schools to emphasize legal teaching by full-time professors instead of practitioners, a system that is still followed today. The Wharton School was home to several pioneering developments in business education. It established the first research center in a business school in 1921 and the first center for entrepreneurship center in 1973 and it regularly introduced novel curricula for which BusinessWeek wrote, “Wharton is on the crest of a wave of reinvention and change in management education”.

Several major scientific discoveries have also taken place at Penn. The university is probably best known as the place where the first general-purpose electronic computer (ENIAC) was born in 1946 at the Moore School of Electrical Engineering.

ENIAC UPenn

It was here also where the world’s first spelling and grammar checkers were created, as well as the popular COBOL programming language. Penn can also boast some of the most important discoveries in the field of medicine. The dialysis machine used as an artificial replacement for lost kidney function was conceived and devised out of a pressure cooker by William Inouye while he was still a student at Penn Med; the Rubella and Hepatitis B vaccines were developed at Penn; the discovery of cancer’s link with genes; cognitive therapy; Retin-A (the cream used to treat acne), Resistin; the Philadelphia gene (linked to chronic myelogenous leukemia) and the technology behind PET Scans were all discovered by Penn Med researchers. More recent gene research has led to the discovery of the genes for fragile X syndrome, the most common form of inherited mental retardation; spinal and bulbar muscular atrophy, a disorder marked by progressive muscle wasting; and Charcot–Marie–Tooth disease, a progressive neurodegenerative disease that affects the hands, feet and limbs.

Conductive polymer was also developed at Penn by Alan J. Heeger, Alan MacDiarmid and Hideki Shirakawa, an invention that earned them the Nobel Prize in Chemistry. On faculty since 1965, Ralph L. Brinster developed the scientific basis for in vitro fertilization and the transgenic mouse at Penn and was awarded the National Medal of Science in 2010. The theory of superconductivity was also partly developed at Penn, by then-faculty member John Robert Schrieffer (along with John Bardeen and Leon Cooper). The university has also contributed major advancements in the fields of economics and management. Among the many discoveries are conjoint analysis, widely used as a predictive tool especially in market research; Simon Kuznets’s method of measuring Gross National Product; the Penn effect (the observation that consumer price levels in richer countries are systematically higher than in poorer ones) and the “Wharton Model” developed by Nobel-laureate Lawrence Klein to measure and forecast economic activity. The idea behind Health Maintenance Organizations also belonged to Penn professor Robert Eilers, who put it into practice during then-President Nixon’s health reform in the 1970s.

International partnerships

Students can study abroad for a semester or a year at partner institutions such as the London School of Economics(UK), University of Barcelona [Universitat de Barcelona](ES), Paris Institute of Political Studies [Institut d’études politiques de Paris](FR), University of Queensland(AU), University College London(UK), King’s College London(UK), Hebrew University of Jerusalem(IL) and University of Warwick(UK).

From Imperial College London (UK) : “Scientists engineer new tools to electronically control gene expression”

From Imperial College London (UK)

04 May 2022
Ayesha Khan

Researchers have created an improved method for turning genes on and off using electrical signals.

Researchers, led by experts at Imperial College London, have developed a new method that allows gene expression to be precisely altered by supplying and removing electrons.

This could help control biomedical implants in the body or reactions in large ‘bioreactors’ that produce drugs and other useful compounds. Current stimuli used to initiate such reactions are often unable to penetrate materials or pose risk of toxicity – electricity holds the solution.

Gene expression is the process by which genes are ‘activated’ to produce new molecules and other downstream effects in cells. In organisms, it is regulated by regions of the DNA called promoters. Some promoters, called inducible promoters, can respond to different stimuli, such as light, chemicals and temperature.

Using electricity to control gene expression has opened a new field of research and while such electrogenetic systems have been previously identified they have lacked precision during the presence or absence of electrical signals, limiting their applications. The newly proposed system, with engineered promoters, allows such accuracy to be obtained for the first time using electrical stimulus in bacteria.

The research is published today in Science Advances.

Flick of a switch

Co-lead author Joshua Lawrence said: “A major issue in synthetic biology is that it is hard to control biological systems in the way we control artificial ones. If we want to get a cell to produce a specific chemical at a certain time we can’t just change a setting on a computer – we have to add a chemical or change the light conditions.

“The tools we’ve created as part of this project will enable researchers to control the gene expression and behaviour of cells with electrical signals instead without any loss in performance.

“We hope that by further developing these tools we really will be able to control biological systems with a flick of a switch.”

In this research, the PsoxS promoter was redesigned to respond more strongly to electrical stimuli, provided by the delivery of electrons. The newly engineered PsoxS promoters were able not only to activate gene expression but also repress it.

Electrically stimulated gene expression has so far been difficult to conduct in the presence of oxygen, limiting its use in real-life applications. The new method is viable in the presence of oxygen, meaning it can be replicated across different species of bacteria and used in applications such as medical implants and bioindustrial processes.

Electrochemical tools can be adjusted for different tasks by tuning them to a specific level, via change in electrode potential.

Glowing bacteria

Biomedical implants often use a stimulus to produce a certain drug or hormone in the body. Not all stimuli are suitable; light is unable to penetrate the human body and chemical ingestion can lead to toxicity. Electric stimuli can be administered via electrodes, giving direct and safe delivery.

For large bioreactors (sometimes the size of a building), that produce chemicals, drugs or fuels, the large volume of culture can be difficult to penetrate with light and expensive to feed with chemical inducers, so delivery of electrons provides a solution.

For their proof-of-concept study, the researchers took the ‘glowing’ protein from jellyfish, and used the new promoter and electrons to induce its expression in bacteria, making the cells glow only when the system was ‘on’. In a different configuration of the system, researchers created a bacteria that was glowing when the system was ‘off’ and stopped glowing when the system was ‘on’.

Illustration of how the system works. Credit: Imperial College London.

Dr Rodrigo Ledesma Amaro, lecturer at Imperial College London and leader of the RLAlab research group said, “The project originated as a blue sky idea during a synthetic biology student competition.

“Thanks to strong dedication, years of work and a great team effort, that initial idea was turned into a reality and we now have a variety of new technologies to use electricity to control the fate of cells.”

Building a library

The team are now planning on developing different promoters that will act to induce different downstream factors, so that simultaneous electrical signals can express different genes, independent of one another. Building a larger library of promoters and downstream factors means the current system can be adapted for use in yeast, plants and animals.

Dr Ledesma-Amaro, from the Department of Bioengineering at Imperial, supervised the research that was carried out by Joshua Lawrence, currently at The University of Cambridge (UK) and Yutong Yin, currently at The University of Oxford (UK).

The research is the result of a larger collaboration of experts from across Imperial’s Departments of Chemistry, Life Sciences and Bioengineering, the Imperial College Translation & Innovation Hub, Cambridge University and The University of Milan [Università degli Studi di Milano Statale] (IT).

See the full article here.

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition

Imperial College London (UK) is a science-based university with an international reputation for excellence in teaching and research. Consistently rated amongst the world’s best universities, Imperial is committed to developing the next generation of researchers, scientists and academics through collaboration across disciplines. Located in the heart of London, Imperial is a multidisciplinary space for education, research, translation and commercialization, harnessing science and innovation to tackle global challenges.

Imperial College London (legally Imperial College of Science, Technology and Medicine) is a public research university in London. Imperial grew out of Prince Albert’s vision of an area for culture, including the Royal Albert Hall; Imperial Institute; numerous museums and the Royal Colleges that would go on to form the college. In 1907, Imperial College was established by Royal Charter, merging the Royal College of Science; Royal School of Mines; and City and Guilds College. In 1988, the Imperial College School of Medicine was formed by combining with St Mary’s Hospital Medical School. In 2004, Queen Elizabeth II opened the Imperial College Business School.

The college focuses exclusively on science; technology; medicine; and business. The college’s main campus is located in South Kensington, and it has an innovation campus in White City; a research field station at Silwood Park; and teaching hospitals throughout London. The college was a member of the University of London(UK) from 1908, becoming independent on its centenary in 2007. Imperial has an international community, with more than 59% of students from outside the UK and 140 countries represented on campus. Student, staff, and researcher affiliations include 14 Nobel laureates; 3 Fields Medalists; 2 Breakthrough Prize winners; 1 Turing Award winner; 74 Fellows of the Royal Society; 87 Fellows of the Royal Academy of Engineering; and 85 Fellows of the Academy of Medical Sciences.

History

19th century

The earliest college that led to the formation of Imperial was the Royal College of Chemistry founded in 1845 with the support of Prince Albert and parliament. This was merged in 1853 into what became known as the Royal School of Mines. The medical school has roots in many different schools across London, the oldest of which being Charing Cross Hospital Medical School which can be traced back to 1823 followed by teaching starting at Westminster Hospital in 1834 and St Mary’s Hospital in 1851.

In 1851 the Great Exhibition was organised as an exhibition of culture and industry by Henry Cole and by Prince Albert- husband of the reigning monarch of the United Kingdom Queen Victoria. An enormously popular and financial success proceeds from the Great Exhibition were designated to develop an area for cultural and scientific advancement in South Kensington. Within the next 6 years the Victoria and Albert Museum and Science Museum had opened joined by new facilities in 1871 for the Royal College of Chemistry and in 1881 for the Royal School of Mines; the opening of the Natural History Museum in 1881; and in 1888 the Imperial Institute.

In 1881 the Normal School of Science was established in South Kensington under the leadership of Thomas Huxley taking over responsibility for the teaching of the natural sciences and agriculture from the Royal School of Mines. The school was renamed the Royal College of Science by royal consent in 1890. The Central Institution of the City and Guilds of London Institute was opened as a technical education school on Exhibition Road by the Prince of Wales in early 1885.

20th century

At the start of the 20th century, there was a concern that Britain was falling behind Germany in scientific and technical education. A departmental committee was set up at the Board of Education in 1904, to look into the future of the Royal College of Science. A report released in 1906 called for the establishment of an institution unifying the Royal College of Science and the Royal School of Mines, as well as – if an agreement could be reached with the City and Guilds of London Institute – their Central Technical College.

On 8 July 1907 King Edward VII granted a Royal Charter establishing the Imperial College of Science and Technology. This incorporated the Royal School of Mines and the Royal College of Science. It also made provisions for the City and Guilds College to join once conditions regarding its governance were met as well as for Imperial to become a college of the University of London. The college joined the University of London on 22 July 1908 with the City and Guilds College joining in 1910. The main campus of Imperial College was constructed beside the buildings of the Imperial Institute- the new building for the Royal College of Science having opened across from it in 1906 and the foundation stone for the Royal School of Mines building being laid by King Edward VII in July 1909.

As students at Imperial had to study separately for London degrees in January 1919 students and alumni voted for a petition to make Imperial a university with its own degree awarding powers independent of the University of London. In response the University of London changed its regulations in 1925 so that the courses taught only at Imperial would be examined by the university enabling students to gain a BSc.

In October 1945 King George VI and Queen Elizabeth visited Imperial to commemorate the centenary of the Royal College of Chemistry which was the oldest of the institutions that united to form Imperial College. “Commemoration Day” named after this visit is held every October as the university’s main graduation ceremony. The college also acquired a biology field station at Silwood Park near Ascot, Berkshire in 1947.

Following the Second World War, there was again concern that Britain was falling behind in science – this time to the United States. The Percy Report of 1945 and Barlow Committee in 1946 called for a “British MIT”-equivalent backed by influential scientists as politicians of the time including Lord Cherwell; Sir Lawrence Bragg; and Sir Edward Appleton. The University Grants Committee strongly opposed however. So a compromise was reached in 1953 where Imperial would remain within the university but double in size over the next ten years. The expansion led to a number of new buildings being erected. These included the Hill building in 1957 and the Physics building in 1960 and the completion of the East Quadrangle built in four stages between 1959 and 1965. The building work also meant the demolition of the City and Guilds College building in 1962–63 and the Imperial Institute’s building by 1967. Opposition from the Royal Fine Arts Commission and others meant that Queen’s Tower was retained with work carried out between 1966 and 1968 to make it free standing. New laboratories for biochemistry established with the support of a £350,000 grant from the Wolfson Foundation were opened by the Queen in 1965.

In 1988 Imperial merged with St Mary’s Hospital Medical School under the Imperial College Act 1988. Amendments to the royal charter changed the formal name of the institution to The Imperial College of Science Technology and Medicine and made St Mary’s a constituent college. This was followed by mergers with the National Heart and Lung Institute in 1995 and the Charing Cross and Westminster Medical School; Royal Postgraduate Medical School; and the Institute of Obstetrics and Gynaecology in 1997 with the Imperial College Act 1997 formally establishing the Imperial College School of Medicine.

21st century

In 2003, Imperial was granted degree-awarding powers in its own right by the Privy Council. In 2004, the Imperial College Business School and a new main entrance on Exhibition Road were opened by Queen Elizabeth II. The UK Energy Research Centre was also established in 2004 and opened its headquarters at Imperial. On 9 December 2005, Imperial announced that it would commence negotiations to secede from the University of London. Imperial became fully independent of the University of London in July 2007.

In April 2011 Imperial and King’s College London joined the UK Centre for Medical Research and Innovation as partners with a commitment of £40 million each to the project. The centre was later renamed the Francis Crick Institute and opened on 9 November 2016. It is the largest single biomedical laboratory in Europe. The college began moving into the new White City campus in 2016 with the launching of the Innovation Hub. This was followed by the opening of the Molecular Sciences Research Hub for the Department of Chemistry officially opened by Mayor of London- Sadiq Khan in 2019. The White City campus also includes another biomedical centre funded by a £40 million donation by alumnus Sir Michael Uren.

Research

Imperial submitted a total of 1,257 staff across 14 units of assessment to the 2014 Research Excellence Framework (REF) assessment. This found that 91% of Imperial’s research is “world-leading” (46% achieved the highest possible 4* score) or “internationally excellent” (44% achieved 3*) giving an overall GPA of 3.36. In rankings produced by Times Higher Education based upon the REF results Imperial was ranked 2nd overall. Imperial is also widely known to have been a critical contributor of the discovery of penicillin; the invention of fiber optics; and the development of holography. The college promotes research commercialisation partly through its dedicated technology transfer company- Imperial Innovations- which has given rise to a large number of spin-out companies based on academic research. Imperial College has a long-term partnership with the Massachusetts Institute of Technology(US) that dates back from World War II. The United States is the college’s top collaborating foreign country with more than 15,000 articles co-authored by Imperial and U.S.-based authors over the last 10 years.

In January 2018 the mathematics department of Imperial and the CNRS-The National Center for Scientific Research[Centre national de la recherche scientifique](FR) launched UMI Abraham de Moivre at Imperial- a joint research laboratory of mathematics focused on unsolved problems and bridging British and French scientific communities. The Fields medallists Cédric Villani and Martin Hairer hosted the launch presentation. The CNRS-Imperial partnership started a joint PhD program in mathematics and further expanded in June 2020 to include other departments. In October 2018, Imperial College launched the Imperial Cancer Research UK Center- a research collaboration that aims to find innovative ways to improve the precision of cancer treatments inaugurated by former Vice President of the United States Joe Biden as part of his Biden Cancer Initiative.

Imperial was one of the ten leading contributors to the National Aeronautics and Space Administration(US) InSight Mars lander which landed on planet Mars in November 2018, with the college logo appearing on the craft. InSight’s Seismic Experiment for Interior Structure, developed at Imperial, measured the first likely marsquake reading in April 2019. In 2019 it was revealed that the Blackett Laboratory would be constructing an instrument for the European Space Agency [Agence spatiale européenne](EU) Solar Orbiter in a mission to study the Sun, which launched in February 2020. The laboratory is also designing part of the DUNE/LBNF Deep Underground Neutrino Experiment(US).

In early 2020 immunology research at the Faculty of Medicine focused on SARS-CoV-2 under the leadership of Professor Robin Shattock as part of the college’s COVID-19 Response Team including the search of a cheap vaccine which started human trials on 15 June 2020. Professor Neil Ferguson’s 16 March report entitled Impact of non-pharmaceutical interventions (NPIs) to reduce COVID- 19 mortality and healthcare demand was described in a 17 March The New York Times article as the coronavirus “report that jarred the U.S. and the U.K. to action”. Since 18 May 2020 Imperial College’s Dr. Samir Bhatt has been advising the state of New York for its reopening plan. Governor of New York Andrew Cuomo said that “the Imperial College model- as we’ve been following this for weeks- was the best most accurate model.” The hospitals from the Imperial College Healthcare NHS Trust which have been caring for COVID-19 infected patients partnered with Microsoft to use their HoloLens when treating those patients reducing the amount of time spent by staff in high-risk areas by up to 83% as well as saving up to 700 items of PPE per ward, per week.

From The Johns Hopkins University HUB : “Johns Hopkins scientists contribute to first complete sequence of human genome”

From The Johns Hopkins University HUB

3.31.22
Randy Rieland

Credit: Will Kirk / Johns Hopkins University.

The Hopkins team contributed key research to the effort, which will provide a clearer picture of how DNA affects the risks of diseases and how genes are expressed and regulated.

A group of Johns Hopkins University scientists has collaborated with more than 100 researchers around the world to assemble and analyze the first complete sequence of a human genome, two decades after the Human Genome Project produced the first draft.

The work is part of the Telomere to Telomere (T2T) consortium, led by researchers at The National Human Genome Research Institute; The University of California-Santa Cruz; and The University of Washington, Seattle.

Johns Hopkins contributed key research to the effort to decipher our DNA—which has remained a mystery despite the initial progress 20 years ago. The revelations are expected to open new lines of molecular and genetic exploration while providing scientists with a clearer picture of how DNA affects the risks of diseases, and how genes are expressed and regulated.

A package of six papers reporting the achievement appears in today’s issue of Science, along with companion papers in several other journals.

https://doi.org/10.1126/science.abj6987
https://doi.org/10.1126/science.abj5089
https://doi.org/10.1126/science.abj6965
https://doi.org/10.1126/science.abk3112
https://doi.org/10.1126/science.abl3533
https://doi.org/10.1126/science.abl4178

“Opening up these new parts of the genome, we think there will be genetic variation contributing to many different traits and disease risk,” said Rajiv McCoy, an assistant professor in the university’s Department of Biology in the Krieger School of Arts and Sciences whose research focuses on human genetics and evolution. “There’s an aspect of this that’s like, we don’t know yet what we don’t know.”

McCoy and 12 Johns Hopkins researchers worked on different aspects of the international initiative, contributing to the main genome assembly project and to several companion works analyzing what can be learned about patterns of genetic and epigenetic variation from person to person through the newly sequenced sections of the genome.

Winston Timp, associate professor of biomedical engineering in the Whiting School of Engineering, and his graduate student, Ariel Gershman, worked on a part of the project that focused on how the completed genome will enhance understanding of gene regulation and expression–the process of turning genes “on” and “off.”

Johns Hopkins researchers, led by PhD students Samantha Zarate, Stephanie Yan, and Melanie Kirsche, along with postdoctoral researcher Sergey Aganezov, specifically helped demonstrate how having a single complete genome improves the ability of scientists to understand variations in the genomes of individuals from different populations. By analyzing data from more than 3,200 people from around the world, they revealed more than a million genetic variants that were not previously known. To do so, the Hopkins team used the NHGRI Analysis, Visualization, and Informatics Labspace (AnVIL), a cloud-based platform co-lead by Bloomberg Distinguished Professor Michael Schatz, who was also an author of the T2T papers.

The study found that because the previous model, known as the reference genome, was a composite of multiple individuals’ genomes essentially “stitched together,” it created artificial “seams” where the model switches from the genome of one person to another. The new, complete version eliminates those seams and is more representative of what an individual’s actual genome looks like.

Using the new human genome model, the Johns Hopkins contributors also quantified how frequently different versions of the same gene occur in diverse human populations. That serves as an evolutionary record of both random fluctuations and potential natural selection affecting certain parts of the genome.

Coordinating their research during the COVID-19 pandemic through the messaging platform Slack, scientists from 30 different institutions added or corrected more than 200 million DNA base pairs, increasing the total number in the human genome to 3.05 billion. A base pair is two chemical bases bonded to one another to form a “rung” of the DNA ladder. Through the process, they also discovered more than 100 new genes able to produce proteins.

According to Schatz, the sequencing has made accessible a segment of the genome about the same size as one of the larger human chromosomes.

“We’ve effectively added an entirely new human chromosome to our knowledge,” he said. “There’s a lot to be gained and learned from it. There’s this whole new opportunity for discovery.”

At the same time, he said, because errors in the previous sequencing were identified and corrected, scientists now have a more precise view of “clinically relevant genes,” a potential boon to personalized medicine.

Of particular interest to the researchers was an enigmatic component of the genome known as centromeres. They are dense bundles of DNA that hold chromosomes together and play a key role in cell division. Previously, however, they had been considered unmappable because they contain thousands of stretches of DNA sequences that repeat over and over.

Timp explained how this work was empowered by long read sequencing, analogous to jigsaw puzzle pieces. Previously these regions were unresolved because they were so repetitive, so all of the pieces were a single color and shape. “It’s like all you have are pieces that look like blue sky. They’re identical. So, how do you put that together? It becomes almost an impossible problem” he said.

But more sophisticated sequencing technology now enables scientists to make better sense of the once inscrutable region using long reads. “It’s like the puzzle pieces are now really big, like a toddler puzzle,” Timp said. “And we discovered there are some objects in the pieces, say some grass or the sun. It’s not just blue sky.”

Being able to track changes over time in these newly accessible genome regions will allow researchers to make more rigorous comparisons from one generation to the next, of people of different origins, or from species to species.

“Finally from tip to tip; telomere to telomere we have an assembly of the genome we can look at,” Timp said.

One immediate challenge McCoy identified is that clinical labs will need to transition from the previous genome mapping to the new complete version-no small undertaking requiring that they adjust the information they have about the links between genes and diseases.

“There are all sorts of databases and resources that have been built around the previous version, and it can be hard to get people to shift over,” he said. “So one goal of our work now is to encourage these important resources to move over to the new mapping to really empower the community.”

For Schatz, who switched careers from cybersecurity to genomics in 2002 after being inspired by the original Human Genome Project, the comprehensive assembly of the human genome, and his being able to contribute to it, is particularly gratifying.

“I always believed this could be done,” he said. “But I don’t think anyone really knew when it could be done and what it would really take. I thought it was going to take many more years. It really was a surprise to me how quickly we could get through it.

See the full article here .

See also the article from University of Washington Medicine here.

See also the full article from University of California-Santa Cruz here.

See also the full article from The National Institutes of Health here .

five-ways-keep-your-child-safe-school-shootings
Please help promote STEM in your local schools.

Stem Education Coalition

About the The Johns Hopkins University HUB

We’ve been doing some thinking — quite a bit, actually — about all the things that go on at Johns Hopkins. Discovering the glue that holds the universe together, for example. Or unraveling the mysteries of Alzheimer’s disease. Or studying butterflies in flight to fine-tune the construction of aerial surveillance robots. Heady stuff, and a lot of it.

In fact, Johns Hopkins does so much, in so many places, that it’s hard to wrap your brain around it all. It’s too big, too disparate, too far-flung.

We created the Hub to be the news center for all this diverse, decentralized activity, a place where you can see what’s new, what’s important, what Johns Hopkins is up to that’s worth sharing. It’s where smart people (like you) can learn about all the smart stuff going on here.

At the Hub, you might read about cutting-edge cancer research or deep-trench diving vehicles or bionic arms. About the psychology of hoarders or the delicate work of restoring ancient manuscripts or the mad motor-skills brilliance of a guy who can solve a Rubik’s Cube in under eight seconds.

There’s no telling what you’ll find here because there’s no way of knowing what Johns Hopkins will do next. But when it happens, this is where you’ll find it.

Johns Hopkins University campus

The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

The Johns Hopkins University is a private research university in Baltimore, Maryland. Founded in 1876, the university was named for its first benefactor, the American entrepreneur and philanthropist Johns Hopkins. His $7 million bequest (approximately $147.5 million in today’s currency)—of which half financed the establishment of the Johns Hopkins Hospital—was the largest philanthropic gift in the history of the United States up to that time. Daniel Coit Gilman, who was inaugurated as the institution’s first president on February 22, 1876, led the university to revolutionize higher education in the U.S. by integrating teaching and research. Adopting the concept of a graduate school from Germany’s historic Ruprecht Karl University of Heidelberg, [Ruprecht-Karls-Universität Heidelberg] (DE), Johns Hopkins University is considered the first research university in the United States. Over the course of several decades, the university has led all U.S. universities in annual research and development expenditures. In fiscal year 2016, Johns Hopkins spent nearly $2.5 billion on research. The university has graduate campuses in Italy, China, and Washington, D.C., in addition to its main campus in Baltimore.

Johns Hopkins is organized into 10 divisions on campuses in Maryland and Washington, D.C., with international centers in Italy and China. The two undergraduate divisions, the Zanvyl Krieger School of Arts and Sciences and the Whiting School of Engineering, are located on the Homewood campus in Baltimore’s Charles Village neighborhood. The medical school, nursing school, and Bloomberg School of Public Health, and Johns Hopkins Children’s Center are located on the Medical Institutions campus in East Baltimore. The university also consists of the Peabody Institute, Applied Physics Laboratory, Paul H. Nitze School of Advanced International Studies, School of Education, Carey Business School, and various other facilities.

Johns Hopkins was a founding member of the American Association of Universities. As of October 2019, 39 Nobel laureates and 1 Fields Medalist have been affiliated with Johns Hopkins. Founded in 1883, the Blue Jays men’s lacrosse team has captured 44 national titles and plays in the Big Ten Conference as an affiliate member as of 2014.

Research

The opportunity to participate in important research is one of the distinguishing characteristics of Hopkins’ undergraduate education. About 80 percent of undergraduates perform independent research, often alongside top researchers. In FY 2013, Johns Hopkins received $2.2 billion in federal research grants—more than any other U.S. university for the 35th consecutive year. Johns Hopkins has had seventy-seven members of the Institute of Medicine, forty-three Howard Hughes Medical Institute Investigators, seventeen members of the National Academy of Engineering, and sixty-two members of the National Academy of Sciences. As of October 2019, 39 Nobel Prize winners have been affiliated with the university as alumni, faculty members or researchers, with the most recent winners being Gregg Semenza and William G. Kaelin.

Between 1999 and 2009, Johns Hopkins was among the most cited institutions in the world. It attracted nearly 1,222,166 citations and produced 54,022 papers under its name, ranking No. 3 globally [after Harvard University and the Max Planck Society (DE)] in the number of total citations published in Thomson Reuters-indexed journals over 22 fields in America.

In FY 2000, Johns Hopkins received $95.4 million in research grants from the National Aeronautics and Space Administration, making it the leading recipient of NASA research and development funding. In FY 2002, Hopkins became the first university to cross the $1 billion threshold on either list, recording $1.14 billion in total research and $1.023 billion in federally sponsored research. In FY 2008, Johns Hopkins University performed $1.68 billion in science, medical and engineering research, making it the leading U.S. academic institution in total R&D spending for the 30th year in a row, according to a National Science Foundation ranking. These totals include grants and expenditures of JHU’s Applied Physics Laboratory in Laurel, Maryland.

The Johns Hopkins University also offers the “Center for Talented Youth” program—a nonprofit organization dedicated to identifying and developing the talents of the most promising K-12 grade students worldwide. As part of the Johns Hopkins University, the “Center for Talented Youth” or CTY helps fulfill the university’s mission of preparing students to make significant future contributions to the world. The Johns Hopkins Digital Media Center (DMC) is a multimedia lab space as well as an equipment, technology and knowledge resource for students interested in exploring creative uses of emerging media and use of technology.

In 2013, the Bloomberg Distinguished Professorships program was established by a $250 million gift from Michael Bloomberg. This program enables the university to recruit fifty researchers from around the world to joint appointments throughout the nine divisions and research centers. Each professor must be a leader in interdisciplinary research and be active in undergraduate education. Directed by Vice Provost for Research Denis Wirtz, there are currently thirty two Bloomberg Distinguished Professors at the university, including three Nobel Laureates, eight fellows of the American Association for the Advancement of Science, ten members of the American Academy of Arts and Sciences, and thirteen members of the National Academies.

From The Massachusetts Institute of Technology: “How molecular biology could reduce global food insecurity” Mary Gehring

From The Massachusetts Institute of Technology

March 29, 2022
Summer Weidman | Abdul Latif Jameel Water and Food Systems Lab

Mary Gehring is using her background in plant epigenetics to grow climate-resilient crops.

Mary Gehring, associate professor of biology and a member of the Whitehead Institute for Biomedical Research
Photo courtesy of J-WAFS.

Staple crops like rice, maize, and wheat feed over half of the global population, but they are increasingly vulnerable to severe environmental risks. The effects of climate change, including changing temperatures, rainfall variability, shifting patterns of agricultural pests and diseases, and saltwater intrusion from sea-level rise, all contribute to decreased crop yields. As these effects continue to worsen, there will be less food available for a rapidly growing population.

Mary Gehring, associate professor of biology and a member of the Whitehead Institute for Biomedical Research, is growing increasingly concerned about the potentially catastrophic impacts of climate change and resolved to do something about it.

The Gehring Lab’s primary research focus is plant epigenetics, which refers to the heritable information that influences plant cellular function but is not encoded in the DNA sequence itself. This research is adding to our fundamental understanding of plant biology and could have agricultural applications in the future. “I’ve been working with seeds for many years,” says Gehring. “Understanding how seeds work is going to be critical to agriculture and food security,” she explains.

Laying the foundation

Gehring is using her expertise to help crops develop climate resilience through a 2021 seed grant from MIT’s Abdul Latif Jameel Water and Food Systems Lab (J-WAFS). Her research is aimed at discovering how we can accelerate the production of genetic diversity to generate plant populations that are better suited to challenging environmental conditions.

Genetic variation gives rise to phenotypic variations that can help plants adapt to a wider range of climates. Traits such as flood resistance and salt tolerance will become more important as the effects of climate change are realized. However, many important plant species do not appear to have much standing genetic variation, which could become an issue if farmers need to breed their crops quickly to adapt to a changing climate.

In researching a nutritious crop that has little genetic variation, Gehring came across the pigeon pea, a species she had never worked with before. Pigeon peas are a legume eaten in Asia, Africa, and Latin America. They have some of the highest levels of protein in a seed, so eating more pigeon peas could decrease our dependence on meat, which has numerous negative environmental impacts. Pigeon peas also have a positive impact on the environment; as perennial plants, they live for three to five years and sequester carbon for longer periods of time. They can also help with soil restoration. “Legumes are very interesting because they’re nitrogen-fixers, so they create symbioses with microbes in the soil and fix nitrogen, which can renew soils,” says Gehring. Furthermore, pigeon peas are known to be drought-resistant, so they will likely become more attractive as many farmers transition away from water-intensive crops.

Developing a strategy

Using the pigeon pea plant, Gehring began to explore a universal technology that would increase the amount of genetic diversity in plants. One method her research group chose is to enhance transposable element proliferation. Both human and plant genomes are made up of genes that code for proteins, but large fractions of the genome are also made up of transposable elements. In fact, about 45 percent of the human genome is made up of transposable elements, Gehring notes. Transposable elements can make multiple copies of themselves, move around, and alter gene expression. Since humans and plants do not need an infinite number of these copies, there are systems in place to “silence” them from copying.

Gehring is trying to reverse that silencing in plants so that the transposable elements can move freely throughout the genome, which could increase genetic variation by creating mutations or altering the promoter of a gene — that is, what controls a certain gene’s expression. Scientists have traditionally initiated mutagenesis by using a chemical that changes single base pairs in DNA, or by using X-rays, which can cause very large chromosome breaks. Gehring’s research team is attempting to induce transposable element proliferation by treatment with a suite of chemicals that inhibit transposable element silencing. The goal is to impact multiple sites in the genome simultaneously. “This is unexplored territory where you’re changing 50 genes at a time, or 100, rather than just one,” she explains. “It’s a fairly risky project, but sometimes you have to be ambitious and take risks.”

Looking forward

Less than one year after receiving the J-WAFS seed grant, the research project is still in its early stages. Despite various restrictions due to the ongoing pandemic, the Gehring Lab is now generating data on the Arabidopsis plant that will be applied to pigeon pea plants. However, Gehring expects it will take a good amount of time to complete this research phase, considering the pigeon pea plants can take upward of 100 days just to flower. While it might take time, this technology could help crops withstand the effects of climate change, ultimately contributing to J-WAFS’ goal of finding solutions to food system challenges.

“Climate change is not something any of us can ignore. … If one of us has the ability to address it, even in a very small way, that’s important to try to pursue,” Gehring remarks. “It’s part of our responsibility as scientists to take what knowledge we have and try to apply it to these sorts of problems.”

See the full article here .

five-ways-keep-your-child-safe-school-shootings
Please help promote STEM in your local schools.

Stem Education Coalition

USPS “Forever” postage stamps celebrating Innovation at MIT.

The Massachusetts Institute of Technology is a private land-grant research university in Cambridge, Massachusetts. The institute has an urban campus that extends more than a mile (1.6 km) alongside the Charles River. The institute also encompasses a number of major off-campus facilities such as the MIT Lincoln Laboratory , the MIT Bates Research and Engineering Center , and the Haystack Observatory , as well as affiliated laboratories such as the Broad Institute of MIT and Harvard and Whitehead Institute.

Massachusettes Institute of Technology-Haystack Observatory Westford, Massachusetts, USA, Altitude 131 m (430 ft).

Founded in 1861 in response to the increasing industrialization of the United States, Massachusetts Institute of Technology adopted a European polytechnic university model and stressed laboratory instruction in applied science and engineering. It has since played a key role in the development of many aspects of modern science, engineering, mathematics, and technology, and is widely known for its innovation and academic strength. It is frequently regarded as one of the most prestigious universities in the world.

As of December 2020, 97 Nobel laureates, 26 Turing Award winners, and 8 Fields Medalists have been affiliated with MIT as alumni, faculty members, or researchers. In addition, 58 National Medal of Science recipients, 29 National Medals of Technology and Innovation recipients, 50 MacArthur Fellows, 80 Marshall Scholars, 3 Mitchell Scholars, 22 Schwarzman Scholars, 41 astronauts, and 16 Chief Scientists of the U.S. Air Force have been affiliated with The Massachusetts Institute of Technology . The university also has a strong entrepreneurial culture and MIT alumni have founded or co-founded many notable companies. Massachusetts Institute of Technology is a member of the Association of American Universities (AAU).

Foundation and vision

In 1859, a proposal was submitted to the Massachusetts General Court to use newly filled lands in Back Bay, Boston for a “Conservatory of Art and Science”, but the proposal failed. A charter for the incorporation of the Massachusetts Institute of Technology, proposed by William Barton Rogers, was signed by John Albion Andrew, the governor of Massachusetts, on April 10, 1861.

Rogers, a professor from the University of Virginia , wanted to establish an institution to address rapid scientific and technological advances. He did not wish to found a professional school, but a combination with elements of both professional and liberal education, proposing that:

“The true and only practicable object of a polytechnic school is, as I conceive, the teaching, not of the minute details and manipulations of the arts, which can be done only in the workshop, but the inculcation of those scientific principles which form the basis and explanation of them, and along with this, a full and methodical review of all their leading processes and operations in connection with physical laws.”

The Rogers Plan reflected the German research university model, emphasizing an independent faculty engaged in research, as well as instruction oriented around seminars and laboratories.

Early developments

Two days after The Massachusetts Institute of Technology was chartered, the first battle of the Civil War broke out. After a long delay through the war years, MIT’s first classes were held in the Mercantile Building in Boston in 1865. The new institute was founded as part of the Morrill Land-Grant Colleges Act to fund institutions “to promote the liberal and practical education of the industrial classes” and was a land-grant school. In 1863 under the same act, the Commonwealth of Massachusetts founded the Massachusetts Agricultural College, which developed as the University of Massachusetts Amherst . In 1866, the proceeds from land sales went toward new buildings in the Back Bay.

The Massachusetts Institute of Technology was informally called “Boston Tech”. The institute adopted the European polytechnic university model and emphasized laboratory instruction from an early date. Despite chronic financial problems, the institute saw growth in the last two decades of the 19th century under President Francis Amasa Walker. Programs in electrical, chemical, marine, and sanitary engineering were introduced, new buildings were built, and the size of the student body increased to more than one thousand.

The curriculum drifted to a vocational emphasis, with less focus on theoretical science. The fledgling school still suffered from chronic financial shortages which diverted the attention of the MIT leadership. During these “Boston Tech” years, Massachusetts Institute of Technology faculty and alumni rebuffed Harvard University president (and former MIT faculty) Charles W. Eliot’s repeated attempts to merge MIT with Harvard College’s Lawrence Scientific School. There would be at least six attempts to absorb MIT into Harvard. In its cramped Back Bay location, MIT could not afford to expand its overcrowded facilities, driving a desperate search for a new campus and funding. Eventually, the MIT Corporation approved a formal agreement to merge with Harvard, over the vehement objections of MIT faculty, students, and alumni. However, a 1917 decision by the Massachusetts Supreme Judicial Court effectively put an end to the merger scheme.

In 1916, The Massachusetts Institute of Technology administration and the MIT charter crossed the Charles River on the ceremonial barge Bucentaur built for the occasion, to signify MIT’s move to a spacious new campus largely consisting of filled land on a one-mile-long (1.6 km) tract along the Cambridge side of the Charles River. The neoclassical “New Technology” campus was designed by William W. Bosworth and had been funded largely by anonymous donations from a mysterious “Mr. Smith”, starting in 1912. In January 1920, the donor was revealed to be the industrialist George Eastman of Rochester, New York, who had invented methods of film production and processing, and founded Eastman Kodak. Between 1912 and 1920, Eastman donated $20 million ($236.6 million in 2015 dollars) in cash and Kodak stock to MIT.

Curricular reforms

In the 1930s, President Karl Taylor Compton and Vice-President (effectively Provost) Vannevar Bush emphasized the importance of pure sciences like physics and chemistry and reduced the vocational practice required in shops and drafting studios. The Compton reforms “renewed confidence in the ability of the Institute to develop leadership in science as well as in engineering”. Unlike Ivy League schools, Massachusetts Institute of Technology catered more to middle-class families, and depended more on tuition than on endowments or grants for its funding. The school was elected to the Association of American Universities in 1934.

Still, as late as 1949, the Lewis Committee lamented in its report on the state of education at The Massachusetts Institute of Technology that “the Institute is widely conceived as basically a vocational school”, a “partly unjustified” perception the committee sought to change. The report comprehensively reviewed the undergraduate curriculum, recommended offering a broader education, and warned against letting engineering and government-sponsored research detract from the sciences and humanities. The School of Humanities, Arts, and Social Sciences and the MIT Sloan School of Management were formed in 1950 to compete with the powerful Schools of Science and Engineering. Previously marginalized faculties in the areas of economics, management, political science, and linguistics emerged into cohesive and assertive departments by attracting respected professors and launching competitive graduate programs. The School of Humanities, Arts, and Social Sciences continued to develop under the successive terms of the more humanistically oriented presidents Howard W. Johnson and Jerome Wiesner between 1966 and 1980.

The Massachusetts Institute of Technology‘s involvement in military science surged during World War II. In 1941, Vannevar Bush was appointed head of the federal Office of Scientific Research and Development and directed funding to only a select group of universities, including MIT. Engineers and scientists from across the country gathered at Massachusetts Institute of Technology ‘s Radiation Laboratory, established in 1940 to assist the British military in developing microwave radar. The work done there significantly affected both the war and subsequent research in the area. Other defense projects included gyroscope-based and other complex control systems for gunsight, bombsight, and inertial navigation under Charles Stark Draper’s Instrumentation Laboratory; the development of a digital computer for flight simulations under Project Whirlwind; and high-speed and high-altitude photography under Harold Edgerton. By the end of the war, The Massachusetts Institute of Technology became the nation’s largest wartime R&D contractor (attracting some criticism of Bush), employing nearly 4000 in the Radiation Laboratory alone and receiving in excess of $100 million ($1.2 billion in 2015 dollars) before 1946. Work on defense projects continued even after then. Post-war government-sponsored research at MIT included SAGE and guidance systems for ballistic missiles and Project Apollo.

These activities affected The Massachusetts Institute of Technology profoundly. A 1949 report noted the lack of “any great slackening in the pace of life at the Institute” to match the return to peacetime, remembering the “academic tranquility of the prewar years”, though acknowledging the significant contributions of military research to the increased emphasis on graduate education and rapid growth of personnel and facilities. The faculty doubled and the graduate student body quintupled during the terms of Karl Taylor Compton, president of The Massachusetts Institute of Technology between 1930 and 1948; James Rhyne Killian, president from 1948 to 1957; and Julius Adams Stratton, chancellor from 1952 to 1957, whose institution-building strategies shaped the expanding university. By the 1950s, The Massachusetts Institute of Technology no longer simply benefited the industries with which it had worked for three decades, and it had developed closer working relationships with new patrons, philanthropic foundations and the federal government.

In late 1960s and early 1970s, student and faculty activists protested against the Vietnam War and The Massachusetts Institute of Technology ‘s defense research. In this period Massachusetts Institute of Technology’s various departments were researching helicopters, smart bombs and counterinsurgency techniques for the war in Vietnam as well as guidance systems for nuclear missiles. The Union of Concerned Scientists was founded on March 4, 1969 during a meeting of faculty members and students seeking to shift the emphasis on military research toward environmental and social problems. The Massachusetts Institute of Technology ultimately divested itself from the Instrumentation Laboratory and moved all classified research off-campus to the MIT Lincoln Laboratory facility in 1973 in response to the protests. The student body, faculty, and administration remained comparatively unpolarized during what was a tumultuous time for many other universities. Johnson was seen to be highly successful in leading his institution to “greater strength and unity” after these times of turmoil. However six Massachusetts Institute of Technology students were sentenced to prison terms at this time and some former student leaders, such as Michael Albert and George Katsiaficas, are still indignant about MIT’s role in military research and its suppression of these protests. (Richard Leacock’s film, November Actions, records some of these tumultuous events.)

In the 1980s, there was more controversy at The Massachusetts Institute of Technology over its involvement in SDI (space weaponry) and CBW (chemical and biological warfare) research. More recently, The Massachusetts Institute of Technology’s research for the military has included work on robots, drones and ‘battle suits’.

Recent history

The Massachusetts Institute of Technology has kept pace with and helped to advance the digital age. In addition to developing the predecessors to modern computing and networking technologies, students, staff, and faculty members at Project MAC, the Artificial Intelligence Laboratory, and the Tech Model Railroad Club wrote some of the earliest interactive computer video games like Spacewar! and created much of modern hacker slang and culture. Several major computer-related organizations have originated at MIT since the 1980s: Richard Stallman’s GNU Project and the subsequent Free Software Foundation were founded in the mid-1980s at the AI Lab; the MIT Media Lab was founded in 1985 by Nicholas Negroponte and Jerome Wiesner to promote research into novel uses of computer technology; the World Wide Web Consortium standards organization was founded at the Laboratory for Computer Science in 1994 by Tim Berners-Lee; the MIT OpenCourseWare project has made course materials for over 2,000 Massachusetts Institute of Technology classes available online free of charge since 2002; and the One Laptop per Child initiative to expand computer education and connectivity to children worldwide was launched in 2005.

The Massachusetts Institute of Technology was named a sea-grant college in 1976 to support its programs in oceanography and marine sciences and was named a space-grant college in 1989 to support its aeronautics and astronautics programs. Despite diminishing government financial support over the past quarter century, MIT launched several successful development campaigns to significantly expand the campus: new dormitories and athletics buildings on west campus; the Tang Center for Management Education; several buildings in the northeast corner of campus supporting research into biology, brain and cognitive sciences, genomics, biotechnology, and cancer research; and a number of new “backlot” buildings on Vassar Street including the Stata Center. Construction on campus in the 2000s included expansions of the Media Lab, the Sloan School’s eastern campus, and graduate residences in the northwest. In 2006, President Hockfield launched the MIT Energy Research Council to investigate the interdisciplinary challenges posed by increasing global energy consumption.

In 2001, inspired by the open source and open access movements, The Massachusetts Institute of Technology launched OpenCourseWare to make the lecture notes, problem sets, syllabi, exams, and lectures from the great majority of its courses available online for no charge, though without any formal accreditation for coursework completed. While the cost of supporting and hosting the project is high, OCW expanded in 2005 to include other universities as a part of the OpenCourseWare Consortium, which currently includes more than 250 academic institutions with content available in at least six languages. In 2011, The Massachusetts Institute of Technology announced it would offer formal certification (but not credits or degrees) to online participants completing coursework in its “MITx” program, for a modest fee. The “edX” online platform supporting MITx was initially developed in partnership with Harvard and its analogous “Harvardx” initiative. The courseware platform is open source, and other universities have already joined and added their own course content. In March 2009 the Massachusetts Institute of Technology faculty adopted an open-access policy to make its scholarship publicly accessible online.

The Massachusetts Institute of Technology has its own police force. Three days after the Boston Marathon bombing of April 2013, MIT Police patrol officer Sean Collier was fatally shot by the suspects Dzhokhar and Tamerlan Tsarnaev, setting off a violent manhunt that shut down the campus and much of the Boston metropolitan area for a day. One week later, Collier’s memorial service was attended by more than 10,000 people, in a ceremony hosted by the Massachusetts Institute of Technology community with thousands of police officers from the New England region and Canada. On November 25, 2013, The Massachusetts Institute of Technology announced the creation of the Collier Medal, to be awarded annually to “an individual or group that embodies the character and qualities that Officer Collier exhibited as a member of The Massachusetts Institute of Technology community and in all aspects of his life”. The announcement further stated that “Future recipients of the award will include those whose contributions exceed the boundaries of their profession, those who have contributed to building bridges across the community, and those who consistently and selflessly perform acts of kindness”.

In September 2017, the school announced the creation of an artificial intelligence research lab called the MIT-IBM Watson AI Lab. IBM will spend $240 million over the next decade, and the lab will be staffed by MIT and IBM scientists. In October 2018 MIT announced that it would open a new Schwarzman College of Computing dedicated to the study of artificial intelligence, named after lead donor and The Blackstone Group CEO Stephen Schwarzman. The focus of the new college is to study not just AI, but interdisciplinary AI education, and how AI can be used in fields as diverse as history and biology. The cost of buildings and new faculty for the new college is expected to be $1 billion upon completion.

The Caltech/MIT Advanced aLIGO was designed and constructed by a team of scientists from California Institute of Technology , Massachusetts Institute of Technology, and industrial contractors, and funded by the National Science Foundation .

Caltech /MIT Advanced aLigo

It was designed to open the field of gravitational-wave astronomy through the detection of gravitational waves predicted by general relativity. Gravitational waves were detected for the first time by the LIGO detector in 2015. For contributions to the LIGO detector and the observation of gravitational waves, two Caltech physicists, Kip Thorne and Barry Barish, and Massachusetts Institute of Technology physicist Rainer Weiss won the Nobel Prize in physics in 2017. Weiss, who is also a Massachusetts Institute of Technology graduate, designed the laser interferometric technique, which served as the essential blueprint for the LIGO.

The mission of The Massachusetts Institute of Technology is to advance knowledge and educate students in science, technology, and other areas of scholarship that will best serve the nation and the world in the twenty-first century. We seek to develop in each member of The Massachusetts Institute of Technology community the ability and passion to work wisely, creatively, and effectively for the betterment of humankind.

From The School of Medicine at The University of Washington: “Design of protein binders from target structure alone”

From The School of Medicine

At

The University of Washington

March 24, 2022
Leila Gray
206.475.9809
leilag@uw.edu

Small proteins (darker shade) designed to bind to the insulin receptor (left) and a component of the influenza virus (right). Credit: Ian C. Haydon/Institute for Protein Design

A team of scientists has created a powerful new method for generating protein drugs. Using computers, they designed molecules that can target important proteins in the body, such as the insulin receptor, as well as vulnerable proteins on the surface of viruses. This solves a long-standing challenge in drug development and may lead to new treatments for cancer, diabetes, infection, inflammation, and beyond.

The research, appearing today in the journal Nature, was led by scientists in the laboratory of David Baker, professor of biochemistry at the University of Washington School of Medicine and a recipient of the 2021 Breakthrough Prize in Life Sciences.

U Washington, Dr. David Baker, Baker Lab.

“The ability to generate new proteins that bind tightly and specifically to any molecular target that you want is a paradigm shift in drug development and molecular biology more broadly,” said Baker.

Antibodies are today’s most common protein-based drugs. They typically function by binding to a specific molecular target, which then becomes either activated or deactivated. Antibodies can treat a wide range of health disorders, including COVID-19 and cancer, but generating new ones is challenging. Antibodies can also be costly to manufacture.

A team led by two postdoctoral scholars in the Baker lab, Longxing Cao and Brian Coventry, combined recent advances in the field of computational protein design to arrive at a strategy for creating new proteins that bind molecular targets in a manner similar to antibodies. They developed software that can scan a target molecule, identify potential binding sites, generate proteins targeting those sites, and then screen from millions of candidate binding proteins to identify those most likely to function.

The team used the new software to generate high-affinity binding proteins against 12 distinct molecular targets. These targets include important cellular receptors such as TrkA, EGFR, Tie2, and the insulin receptor, as well proteins on the surface of the influenza virus and SARS-CoV-2 (the virus that causes COVID-19).

“When it comes to creating new drugs, there are easy targets and there are hard targets,” said Cao, who is now an assistant professor at Westlake University. “In this paper, we show that even very hard targets are amenable to this approach. We were able to make binding proteins to some targets that had no known binding partners or antibodies,”

In total, the team produced over half a million candidate binding proteins for the 12 selected molecular targets. Data collected on this large pool of candidate binding proteins was used to improve the overall method.

“We look forward to seeing how these molecules might be used in a clinical context, and more importantly how this new method of designing protein drugs might lead to even more promising compounds in the future,” said Coventry.

The research team included scientists from the University of Washington School of Medicine, Yale University School of Medicine, Stanford University School of Medicine, Ghent University [Universiteit Gent](BE), The Scripps Research Institute, and the National Cancer Institute, among other institutions.

This work was supported in part by The Audacious Project at the Institute for Protein Design, Open Philanthropy Project, National Institutes of Health (HHSN272201700059C, R01AI140245, R01AI150855, R01AG063845), Defense Advanced Research Project Agency (HR0011835403 contract FA8750-17-C-0219), Defense Threat Reduction Agency (HDTRA1-16-C-0029), Schmidt Futures, Gates Ventures, Donald and Jo Anne Petersen Endowment, and an Azure computing gift for COVID-19 research provided by Microsoft.

See the full article here .

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition

The University of Washington School of Medicine (UWSOM) is a large public medical school in the northwest United States, located in Seattle and affiliated with the University of Washington. According to U.S. News & World Report’s 2022 Best Graduate School rankings, University of Washington School of Medicine ranked #1 in the nation for primary care education, and #7 for research.

UWSOM is the first public medical school in the states of Washington, Wyoming, Alaska, Montana, and Idaho. The school maintains a network of teaching facilities in more than 100 towns and cities across the five-state region. As part of this “WWAMI” partnership, medical students from Wyoming, Alaska, Montana, and Idaho spend their first year and a half at The University of Wyoming , The University of Alaska-Anchorage , Montana State University , or The University of Idaho , respectively. In addition, sixty first-year students and forty second-year students from Washington are based at Gonzaga University in Spokane. Preference is given to residents of the WWAMI states.

The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

The University of Washington is a public research university in Seattle, Washington, United States. Founded in 1861, University of Washington is one of the oldest universities on the West Coast; it was established in downtown Seattle approximately a decade after the city’s founding to aid its economic development. Today, the university’s 703-acre main Seattle campus is in the University District above the Montlake Cut, within the urban Puget Sound region of the Pacific Northwest. The university has additional campuses in Tacoma and Bothell. Overall, University of Washington encompasses over 500 buildings and over 20 million gross square footage of space, including one of the largest library systems in the world with more than 26 university libraries, as well as the UW Tower, lecture halls, art centers, museums, laboratories, stadiums, and conference centers. The university offers bachelor’s, master’s, and doctoral degrees through 140 departments in various colleges and schools, sees a total student enrollment of roughly 46,000 annually, and functions on a quarter system.

University of Washington is a member of the Association of American Universities and is classified among “R1: Doctoral Universities – Very high research activity”. According to the National Science Foundation, UW spent $1.41 billion on research and development in 2018, ranking it 5th in the nation. As the flagship institution of the six public universities in Washington state, it is known for its medical, engineering and scientific research as well as its highly competitive computer science and engineering programs. Additionally, University of Washington continues to benefit from its deep historic ties and major collaborations with numerous technology giants in the region, such as Amazon, Boeing, Nintendo, and particularly Microsoft. Paul G. Allen, Bill Gates and others spent significant time at Washington computer labs for a startup venture before founding Microsoft and other ventures. The University of Washington’s 22 varsity sports teams are also highly competitive, competing as the Huskies in the Pac-12 Conference of the NCAA Division I, representing the United States at the Olympic Games, and other major competitions.

The university has been affiliated with many notable alumni and faculty, including 21 Nobel Prize laureates and numerous Pulitzer Prize winners, Fulbright Scholars, Rhodes Scholars and Marshall Scholars.

In 1854, territorial governor Isaac Stevens recommended the establishment of a university in the Washington Territory. Prominent Seattle-area residents, including Methodist preacher Daniel Bagley, saw this as a chance to add to the city’s potential and prestige. Bagley learned of a law that allowed United States territories to sell land to raise money in support of public schools. At the time, Arthur A. Denny, one of the founders of Seattle and a member of the territorial legislature, aimed to increase the city’s importance by moving the territory’s capital from Olympia to Seattle. However, Bagley eventually convinced Denny that the establishment of a university would assist more in the development of Seattle’s economy. Two universities were initially chartered, but later the decision was repealed in favor of a single university in Lewis County provided that locally donated land was available. When no site emerged, Denny successfully petitioned the legislature to reconsider Seattle as a location in 1858.

In 1861, scouting began for an appropriate 10 acres (4 ha) site in Seattle to serve as a new university campus. Arthur and Mary Denny donated eight acres, while fellow pioneers Edward Lander, and Charlie and Mary Terry, donated two acres on Denny’s Knoll in downtown Seattle. More specifically, this tract was bounded by 4th Avenue to the west, 6th Avenue to the east, Union Street to the north, and Seneca Streets to the south.

John Pike, for whom Pike Street is named, was the university’s architect and builder. It was opened on November 4, 1861, as the Territorial University of Washington. The legislature passed articles incorporating the University, and establishing its Board of Regents in 1862. The school initially struggled, closing three times: in 1863 for low enrollment, and again in 1867 and 1876 due to funds shortage. University of Washington awarded its first graduate Clara Antoinette McCarty Wilt in 1876, with a bachelor’s degree in science.

19th century relocation

By the time Washington state entered the Union in 1889, both Seattle and the University had grown substantially. University of Washington’s total undergraduate enrollment increased from 30 to nearly 300 students, and the campus’s relative isolation in downtown Seattle faced encroaching development. A special legislative committee, headed by University of Washington graduate Edmond Meany, was created to find a new campus to better serve the growing student population and faculty. The committee eventually selected a site on the northeast of downtown Seattle called Union Bay, which was the land of the Duwamish, and the legislature appropriated funds for its purchase and construction. In 1895, the University relocated to the new campus by moving into the newly built Denny Hall. The University Regents tried and failed to sell the old campus, eventually settling with leasing the area. This would later become one of the University’s most valuable pieces of real estate in modern-day Seattle, generating millions in annual revenue with what is now called the Metropolitan Tract. The original Territorial University building was torn down in 1908, and its former site now houses the Fairmont Olympic Hotel.

The sole-surviving remnants of Washington’s first building are four 24-foot (7.3 m), white, hand-fluted cedar, Ionic columns. They were salvaged by Edmond S. Meany, one of the University’s first graduates and former head of its history department. Meany and his colleague, Dean Herbert T. Condon, dubbed the columns as “Loyalty,” “Industry,” “Faith”, and “Efficiency”, or “LIFE.” The columns now stand in the Sylvan Grove Theater.

20th century expansion

Organizers of the 1909 Alaska-Yukon-Pacific Exposition eyed the still largely undeveloped campus as a prime setting for their world’s fair. They came to an agreement with Washington’s Board of Regents that allowed them to use the campus grounds for the exposition, surrounding today’s Drumheller Fountain facing towards Mount Rainier. In exchange, organizers agreed Washington would take over the campus and its development after the fair’s conclusion. This arrangement led to a detailed site plan and several new buildings, prepared in part by John Charles Olmsted. The plan was later incorporated into the overall University of Washington campus master plan, permanently affecting the campus layout.

Both World Wars brought the military to campus, with certain facilities temporarily lent to the federal government. In spite of this, subsequent post-war periods were times of dramatic growth for the University. The period between the wars saw a significant expansion of the upper campus. Construction of the Liberal Arts Quadrangle, known to students as “The Quad,” began in 1916 and continued to 1939. The University’s architectural centerpiece, Suzzallo Library, was built in 1926 and expanded in 1935.

After World War II, further growth came with the G.I. Bill. Among the most important developments of this period was the opening of the School of Medicine in 1946, which is now consistently ranked as the top medical school in the United States. It would eventually lead to the University of Washington Medical Center, ranked by U.S. News and World Report as one of the top ten hospitals in the nation.

In 1942, all persons of Japanese ancestry in the Seattle area were forced into inland internment camps as part of Executive Order 9066 following the attack on Pearl Harbor. During this difficult time, university president Lee Paul Sieg took an active and sympathetic leadership role in advocating for and facilitating the transfer of Japanese American students to universities and colleges away from the Pacific Coast to help them avoid the mass incarceration. Nevertheless, many Japanese American students and “soon-to-be” graduates were unable to transfer successfully in the short time window or receive diplomas before being incarcerated. It was only many years later that they would be recognized for their accomplishments during the University of Washington’s Long Journey Home ceremonial event that was held in May 2008.

From 1958 to 1973, the University of Washington saw a tremendous growth in student enrollment, its faculties and operating budget, and also its prestige under the leadership of Charles Odegaard. University of Washington student enrollment had more than doubled to 34,000 as the baby boom generation came of age. However, this era was also marked by high levels of student activism, as was the case at many American universities. Much of the unrest focused around civil rights and opposition to the Vietnam War. In response to anti-Vietnam War protests by the late 1960s, the University Safety and Security Division became the University of Washington Police Department.

Odegaard instituted a vision of building a “community of scholars”, convincing the Washington State legislatures to increase investment in the University. Washington senators, such as Henry M. Jackson and Warren G. Magnuson, also used their political clout to gather research funds for the University of Washington. The results included an increase in the operating budget from $37 million in 1958 to over $400 million in 1973, solidifying University of Washington as a top recipient of federal research funds in the United States. The establishment of technology giants such as Microsoft, Boeing and Amazon in the local area also proved to be highly influential in the University of Washington’s fortunes, not only improving graduate prospects but also helping to attract millions of dollars in university and research funding through its distinguished faculty and extensive alumni network.

21st century

In 1990, the University of Washington opened its additional campuses in Bothell and Tacoma. Although originally intended for students who have already completed two years of higher education, both schools have since become four-year universities with the authority to grant degrees. The first freshman classes at these campuses started in fall 2006. Today both Bothell and Tacoma also offer a selection of master’s degree programs.

In 2012, the University began exploring plans and governmental approval to expand the main Seattle campus, including significant increases in student housing, teaching facilities for the growing student body and faculty, as well as expanded public transit options. The University of Washington light rail station was completed in March 2015, connecting Seattle’s Capitol Hill neighborhood to the University of Washington Husky Stadium within five minutes of rail travel time. It offers a previously unavailable option of transportation into and out of the campus, designed specifically to reduce dependence on private vehicles, bicycles and local King County buses.

University of Washington has been listed as a “Public Ivy” in Greene’s Guides since 2001, and is an elected member of the American Association of Universities. Among the faculty by 2012, there have been 151 members of American Association for the Advancement of Science, 68 members of the National Academy of Sciences, 67 members of the American Academy of Arts and Sciences, 53 members of the National Academy of Medicine, 29 winners of the Presidential Early Career Award for Scientists and Engineers, 21 members of the National Academy of Engineering, 15 Howard Hughes Medical Institute Investigators, 15 MacArthur Fellows, 9 winners of the Gairdner Foundation International Award, 5 winners of the National Medal of Science, 7 Nobel Prize laureates, 5 winners of Albert Lasker Award for Clinical Medical Research, 4 members of the American Philosophical Society, 2 winners of the National Book Award, 2 winners of the National Medal of Arts, 2 Pulitzer Prize winners, 1 winner of the Fields Medal, and 1 member of the National Academy of Public Administration. Among UW students by 2012, there were 136 Fulbright Scholars, 35 Rhodes Scholars, 7 Marshall Scholars and 4 Gates Cambridge Scholars. UW is recognized as a top producer of Fulbright Scholars, ranking 2nd in the US in 2017.

The Academic Ranking of World Universities has consistently ranked University of Washington as one of the top 20 universities worldwide every year since its first release. In 2019, University of Washington ranked 14th worldwide out of 500 by the ARWU, 26th worldwide out of 981 in the Times Higher Education World University Rankings, and 28th worldwide out of 101 in the Times World Reputation Rankings. Meanwhile, QS World University Rankings ranked it 68th worldwide, out of over 900.

U.S. News & World Report ranked University of Washington 8th out of nearly 1,500 universities worldwide for 2021, with University of Washington’s undergraduate program tied for 58th among 389 national universities in the U.S. and tied for 19th among 209 public universities.

In 2019, it ranked 10th among the universities around the world by SCImago Institutions Rankings. In 2017, the Leiden Ranking, which focuses on science and the impact of scientific publications among the world’s 500 major universities, ranked University of Washington 12th globally and 5th in the U.S.

In 2019, Kiplinger Magazine’s review of “top college values” named University of Washington 5th for in-state students and 10th for out-of-state students among U.S. public colleges, and 84th overall out of 500 schools. In the Washington Monthly National University Rankings University of Washington was ranked 15th domestically in 2018, based on its contribution to the public good as measured by social mobility, research, and promoting public service.

The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

From Curtin University(AU): “Rebooting Evolution”

From Curtin University(AU)

25 February 2022

Lucien Wilkinson
Media Consultant
Tel: +61 8 9266 9185
Mob: +61 401 103 683
lucien.wilkinson@curtin.edu.au

Vanessa Beasley
Deputy Director
Tel: +61 8 9266 1811
Mob: +61 466 853 121
vanessa.beasley@curtin.edu.au

The building blocks of life-saving therapeutics could be developed in days instead of years thanks to new software that simulates evolution.

“Proseeker” is the name of a new computational tool that mimics the processes of natural selection producing proteins that can be used for a range of medicinal and household uses.

The enzymes in your laundry detergent, the insulin in your diabetes medication or the antibodies used in cancer therapy are currently made in the laboratory using a painstaking process called directed evolution.

Laboratory evolution mimics natural evolution by making mutations in naturally-sourced proteins and selecting the best mutants, to be mutated and selected again, in a time-intensive and laborious process that creates useful proteins.

Scientists at the ARC Centre of Excellence in Synthetic Biology have now discovered a way to perform the entire process of directed evolution using a computer. It can reduce the time required from many months or even years to just days.

The team was led by Professor Oliver Rackham, Curtin University, in collaboration with Professor Aleksandra Filipovska, the University of Western Australia, and is based at the Harry Perkins Institute of Medical Research in Perth, Western Australia.

To prove how useful this process could be they took a protein with no function at all and gave it the ability to bind DNA.

‘Proteins that bind DNA are currently revolutionising the field of gene therapy where scientists are using them to reverse disease-causing mutations,’ says Professor Rackham. ‘So this could be of great use in the future.

‘Reconstituting the entire process of directed evolution represents a radical advance for the field.’

The work is described in a new paper in Nature Chemical Biology.

See the full article here .

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition

Curtin University (AU) (formerly known as Curtin University of Technology and Western Australian Institute of Technology) is an Australian public research university based in Bentley and Perth, Western Australia. The university is named after the 14th Prime Minister of Australia, John Curtin, and is the largest university in Western Australia, with over 58,000 students (as of 2016).

Curtin would like to pay respect to the indigenous members of our community by acknowledging the traditional owners of the land on which the Perth campus is located, the Wadjuk people of the Nyungar Nation; and on our Kalgoorlie campus, the Wongutha people of the North-Eastern Goldfields.

Curtin was conferred university status after legislation was passed by the Parliament of Western Australia in 1986. Since then, the university has been expanding its presence and has campuses in Singapore, Malaysia, Dubai and Mauritius. It has ties with 90 exchange universities in 20 countries. The University comprises five main faculties with over 95 specialists centres. The University formerly had a Sydney campus between 2005 & 2016. On 17 September 2015, Curtin University Council made a decision to close its Sydney campus by early 2017.

Curtin University is a member of Australian Technology Network (ATN), and is active in research in a range of academic and practical fields, including Resources and Energy (e.g., petroleum gas), Information and Communication, Health, Ageing and Well-being (Public Health), Communities and Changing Environments, Growth and Prosperity and Creative Writing.

It is the only Western Australian university to produce a PhD recipient of the AINSE gold medal, which is the highest recognition for PhD-level research excellence in Australia and New Zealand.

Curtin has become active in research and partnerships overseas, particularly in mainland China. It is involved in a number of business, management, and research projects, particularly in supercomputing, where the university participates in a tri-continental array with nodes in Perth, Beijing, and Edinburgh. Western Australia has become an important exporter of minerals, petroleum and natural gas. The Chinese Premier Wen Jiabao visited the Woodside-funded hydrocarbon research facility during his visit to Australia in 2005.

From Science News (US) : “How the Human Genome Project revolutionized understanding of our DNA”

From Science News (US)

February 9, 2022
Tina Hesman Saey

A century of ingenuity and technology advances taught us to read the stories in our genes.

The iconic double helix, the structure of our DNA, has graced the cover of Science News many times.
Credit: Jeremy Leung.

In October 1990, biologists officially embarked on one of the century’s most ambitious scientific efforts: reading the 3 billion pairs of genetic subunits — the A’s, T’s, C’s and G’s — that make up the human instruction book.

The project promised to blow open our understanding of basic biology, reveal relationships between the myriad forms of life on the planet and transform medicine through insights into genetic diseases and potential cures. When the project was completed in 2003, the scientists having read essentially every letter, President Bill Clinton called it a “stunning and humbling achievement” and predicted it would “revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases.”

Even dreaming up such an endeavor depended on decades of previous discoveries. In 1905, English biologist William Bateson, who championed the work of Austrian monk Gregor Mendel, suggested the term “genetics” for a new field of study focused on heredity and variation. Early the next decade, American biologist Thomas Hunt Morgan and his colleagues showed that genes are carried on chromosomes. Biochemists had been studying DNA for nearly three-quarters of a century when Oswald Avery and his team at The Rockefeller Institute (US) in New York City helped establish in the 1940s that DNA is the genetic material. And perhaps most notable, and famous today, is the 1953 discovery of the double-helix structure of DNA, by James Watson and Francis Crick of The University of Cambridge (UK) and Rosalind Franklin and Maurice Wilkins of King’s College London (UK).

But when the draft of the genetic instruction book was first published, independently by an international collective of academic and government labs called The Human Genome Project and the private company Celera Genomics, led by J. Craig Venter, the text was “as striking for what we don’t see as for what we do,” Science News reported (SN: 2/17/01, p. 100). There were many fewer genes than expected, leaving a puzzle about what all the remaining DNA was for.

In the decades since, scientists have filled in some of that puzzle — identifying a host of genes, for example, that don’t make proteins but are still essential in the body. Other researchers have searched the instruction book to find new treatments for diseases and to figure out how we’re all related — not just people, but all life on planet Earth, past and present.

To explore how far our understanding of our DNA has come, Science News senior writer and molecular biology reporter Tina Hesman Saey talked with Eric Green, director of The National Human Genome Research Institute [NHGRI](US) at The National Institutes of Health (US) in Bethesda, Md. Green got his start in genomics in the lab of Maynard Olson at The Washington University in St. Louis (US), a pioneer in the field. At the same time, Saey was a graduate student in molecular genetics, working down the hall. She remembers as an undergraduate student sequencing the genes of bacteria 50 to 100 chemical subunits, or bases, at a time. “My mind was completely blown by the idea that you could put together 3 billion bases.” The conversation that follows, which has been edited for length and clarity, looks back on the project and ahead to all that’s left to learn. — Elizabeth Quill

Ambitious beginnings

Saey: My first memory of the Human Genome Project was when I was an undergraduate student at The University of Nebraska-Lincoln (US), and I remember Walter Gilbert, who is a Nobel Prize winner, coming and talking about the project. He proposed this really audacious idea of sequencing 3 billion pairs of bases in the human genome — all of our DNA. After Gilbert’s talk, I walked back to the lab with a couple of professors, and they were saying, “This can never happen. It’s going to cost way too much money. There’s just no way we can do this.” So how did you pull it off?

Green: By the time the genome project started in October of 1990, I was working in a cutting-edge genomics lab at Washington University. We were one of the first funded groups to participate in the Human Genome Project. We had some ideas on how to start, and we had really no idea how we were going to pull it off.

It was the overwhelmingly compelling vision for why this was so important that galvanized enthusiasm among not only a group of scientists like myself, but also the funding agencies, the governments, the private funders from around the world, who said, “This seems unimaginable, like putting a person on the moon, but it seems so important. We’ll figure it out.” So it was one of these circumstances where you just get the right people in the right place, get them resourced, get them organized, be willing to do things differently, and then figure it out as you go.

Saey: I got to witness this because I was a graduate student at Washington University, in a lab sequencing the yeast genome. Robert Waterston’s lab, which received one of the first grants from the Human Genome Project, was right across the hall. They started with C. elegans, the roundworm genome. I remember they were starting very methodically, mapping out the genes and then sequencing each piece, marching along. But then, toward the end of the ’90s, there was this shotgun sequencing revolution spearheaded by kind of a controversial figure, Craig Venter. You just shred the genome, throw it all in a sequencing machine and then put it together in the computer. Did that help a lot?

Green: There’s no question it sped things up. What Craig successfully did was to determine that there were approaches that could be used where you didn’t have to do piecemeal sequencing. The important nuance to point out is the only way you’re able to put [the pieces] back together then was by having many mapping elements that allow you to hang pieces together and organize them. It’s not like it all zipped together 3 billion letters. A lot of the meticulous mapping that had been done, painstaking mapping, helped provide organizing guideposts.

The press covered it as a race, and the press covered it as option A versus option B. And the truth resided somewhere in between. What was driving the change, of course, was technology advances. If you chart the time since the end of the Human Genome Project, it’s the same phenomenon. Every single time there’s a technology surge, you find yourself doing things completely different than the way you used to.

Saey: Technology has come a very long way from what I was doing. You can sequence thousands of bases at a time now.

Green: The other part of the story that sometimes doesn’t get told: It’s not even just the laboratory bench–based technologies. It’s also the computational technologies. Some people don’t realize that when the Human Genome Project started, there was not really a widely functional internet. I was just barely starting to use e-mail.

So here it was, we were one of the first funded groups for the Human Genome Project. We were considered state of the art. We were collaborating with an outside group generating some sequences, and the only practical way for my collaborator to get me the 300 to 400 bases of sequence was to handwrite it on a piece of paper and fax it to me. And I would analyze it by eye. It’s just remarkable that that was where we were when the project started.

Eric Green (right) and his mentor, genomics pioneer Maynard Olson, were key players in the Human Genome Project. Below, the two review data to develop genome-mapping strategies slightly before the 1990 start of the project. Courtesy of NHGRI.

Garbage to gold mine

Saey: In 2000 was the big press conference to announce the rough draft of the human genome. I was just starting my journalism career at The St. Louis Post-Dispatch, and reported on this. At that time, it was a big revelation that there were these big deserts in between genes, and that we didn’t have nearly as many genes as we thought we were going to. Humans are such complex organisms, how could we not have many more genes than a fruit fly, or a worm? That just didn’t make sense.

But now, I think, we are getting a better understanding, largely because of the way we can analyze the genome. Can you talk about how that evolution in thinking has progressed?

Green: Before the genome project started, some [people] were quite critical, and really said it was a bad idea. Some argued that it was a waste of time to sequence the genome end to end; we should just focus and sequence the genes, as if all of humans’ biological richness was going to reside in the genes. Thank goodness we didn’t listen to those critics. Because if we would have done the shortcut and only focused on the genes, we would have only skimmed the biological complexity of humans.

What we’ve come to learn is that while only 1.5 percent of the letters of the human genome directly encode for what are classically known as protein-coding genes — DNA that gets made into RNA, which gets made into protein — there’s a much larger fraction of the human genome that is biologically important and evolutionarily conserved. It’s widened our definition of a gene, because we now know that sometimes DNA may make RNA, and RNA may go off and do all sorts of biological things.

Then there’s a whole set of sequences that are far more plentiful than gene sequences, that are really doing all the choreography in our genomes in terms of determining when, where and how much genes get turned on, in what cells and what tissues, at what developmental stages, under what conditions, and so on and so forth.

It pushed us to think about all the other biological functions in DNA outside the genes. And as you accurately point out, we don’t really have a rulebook for that. And thank goodness the computer technology is helping us because the human eye would just fail miserably at figuring this out. And so as much as anything, computational biology, bioinformatics, data science are the dominant research tools to help bring clarity as to how noncoding sequences in the human genome function. And how they do that in a very carefully crafted choreography with the genes.

Saey: Well, I’m glad you brought up those sequences, because those are some of my favorites. I’m a huge fan of noncoding RNAs [the RNAs that don’t go on to make proteins]. There are so many of them, and such a huge variety of them. And they work in so many important ways (SN: 4/13/19, p. 22).

I don’t think that 20 years ago we could have conceived that RNAs that didn’t make proteins would actually be important for something. The genes those RNAs were copied from were considered broken genes or pseudogenes. They were junk.

Green: Or sloppy transcription; that our enzymes are just going off and making a bunch of RNA because they don’t know how to control themselves. But, no. And I like your point about 20 years ago, we couldn’t imagine. I would propose that 20 years from now, we might look back at this conversation and say, “Oh, my goodness, think about all these other ways that the genome functions.” There’s no reason to think we have our hands around it all in terms of all the biological complexity of DNA; I’m quite sure we don’t.

Saey: And even when you find a protein-coding gene, you’re not just making one protein. You’re making, on average, seven or eight different versions of this protein from the same gene. After RNA gets copied from DNA, you can mix and match the little parts of a gene to make completely new proteins. And then you can tack on all of these other little chemical groups to change the way things work.

Green: When I was getting my Ph.D. at Washington University in the 1980s, I didn’t work on DNA, I didn’t work on molecular biology, I didn’t work on RNA. I was working on a set of proteins, studying how they had sugar molecules added to them after they were made, and how, depending upon what tissue they were made in, they got different structures of sugar molecules attached. So just as you point out, you start off with one gene, and you can end up with multiple RNAs that lead to multiple different proteins. And each of those proteins could have different modifications depending on what tissue, what conditions, what development stage, et cetera. This is the incredible amplification of complexity. It’s not in our gene number. We have a long way to go to fully understanding all this.

Saey: Another thing that really surprises people is how much of our genome is made of extinct viruses and transposons — transposons being these jumping genes that still hop around in our genome. Those transposons can occasionally cause problems, but we also got a lot of innovations from them, including the human placenta, and maybe some things about the way our brain works. So, we’re not even completely human. If you want to view it that way, we’re a lot virus.

Green: Right. We’re a lot virus. We’re also not all Homo sapiens. Many, many people carry Neandertal bits from a time when Neandertals and Homo sapiens coexisted, and actually interbred (SN: 5/8/21 & 5/22/21, p. 7). But not everybody in the world has that, which is also interesting. One of the aspects of genomics is that it not only has taught us and given us the biological instruction book, it’s also given us a fascinating record of evolution. We can use it to learn lots of things about our evolution, about human migrations, about aspects of humans on this globe.

Focus on diversity

Saey: Most people who are interacting with DNA and with the human genome these days do it through ancestry testing and consumer DNA testing. So you can identify the part of the world that people’s DNA came from. And that gets into a lot of discussion about race, and whether race has a biological basis, and what that might mean for medicine.

There’s been a lot of criticism lately of genetics and genomics, because it’s based a lot on the DNA of people of European ancestry — white people like you and me. But there’s a huge amount of genetic diversity in the world among humans, and especially in Africa, where humans got started. So what are we doing about getting a handle on the vast array of diversity that humans have?

Green: There’s no question that the successes in genomics that we’ve been discussing are worth talking about and worth show­casing. At the same time, as a field, we have not been perfect. One of the things that we just have to admit that we’ve really not been as successful on is making sure we’ve captured enough of the diversity of the human population with respect to the samples that we’ve used for doing genetic and genomic studies. We have got to fix this problem. It’s a very high priority.

I really want to emphasize, it’s not even just that it’s the socially right thing to do, that everybody should have information about their genomes. This is very important medically. If the only populations we have a lot of genomic data on are people of European descent, we limit our ability to move genomic analyses and eventually genomic medicine into populations that are not of European descent. And so there’s a high priority through a number of efforts around the world, including in the U.S., to work hard to capture much more diversity of the world’s populations in all studies that we do.

Saey: There’s been a lot of talk about racialized medicine, where you might have a person come in who is African American, and then you would say, “Oh, well, we should consider this to be the genome that we look at.” Is that a good approach to take? Or do you think it should be broader somehow?

Green: The truth is, of course, there are certain diseases that tend to cluster in certain populations of common ancestry. And many times those are represented by racial groups.

But racial grouping is really a social construct that has numerous imperfections. And so on the one hand, you can’t totally ignore some correlations that exist with certain diseases or certain responses to medications in certain groups. But it’s a very blunt tool to use. And we could do better. The way we could do this better is to track much more accurately to specific genomic features, as opposed to certain racial characteristics. So I think what we really want to pay attention to, and we will be doing this increasingly, is thinking about better ways of grouping and stratifying individuals and populations.

Saey: I wanted to touch too on what we mean when we say genetic diversity. For the most part I think people are familiar with what scientists call SNPs, single nucleotide polymorphisms, and what other people might refer to as mutations. But there are lots of other ways that you can have diversity in the genome: You can be missing entire genes or entire chunks of chromosomes or you can have duplications of certain genes. Are we now able to look at that type of diversity as well? And do we know if that’s important?

Green: There’s no question that all forms of genomic diversity — genomic variation is probably the word I would use — are not only biologically relevant, they’re proving to be medically relevant. Now, we don’t have a complete inventory of which ones are more relevant than others. But we already know of many examples where medically relevant variations in our genome can be a single letter, a string of letters, it could mean having extra letters or extra segments, or missing segments. It could be a rearrangement of segments. Every one of those [types of variations] are already known to be important in human disease, and eventually will be important for diagnostic medicine and the implementation of genomic medicine.

Saey: Do you envision a time when we will be able to study and interpret these bigger changes?

Green: I absolutely envision a time where people will get their complete genome sequenced end to end as part of their medical care, and maybe even at birth. I don’t think we’re there yet. But I truly believe that we will want that information as part of medical management. And I fully believe that technologies will become available and will be inexpensive enough to make it worthwhile. But those predictions are going to have to be based on evidence that indeed that’s feasible and valuable.

What’s next?

Saey: So where do we go from here? What does the National Human Genome Research Institute do now that researchers have generated end-to-end sequences of every human chromosome?

Green: We recently finished a two-and-a-half-year strategic planning process to ask that very question for this coming decade. It was actually an overwhelming exercise because there were so many good ideas. We published these in Nature — our 2020 strategic vision. Some of it [is] applications of genomics to medicine. Of course, everybody’s going to be excited about that. But there are many other forefronts of genomics that are just as exciting.

We still don’t have the perfect technologies that we can deploy anywhere in the world in any health setting, any medical study, that will get us end-to-end sequencing. We need better and cheaper technologies for letting us read human genome sequences inexpensively in clinical settings. We need complete end-to-end interpretation of every base of the human genome. We need to know not just about the genes, we need to know about all these noncoding regions. We need to understand every human variant that we can find in the world population. And we need to know: Is that variant biologically silent? Is it biologically relevant? Is it medically relevant? If it’s medically relevant, what’s the action that should be taken? That starts to point us to understanding the genomic basis of disease and also to think about how can we use information about genomic variation in the practice of medicine.

Also, we will continue to think about the implications of these genomic advances to society. How are we going to make sure people understand this? How are we going to make sure things are applied equitably? How are we going to make sure it doesn’t exacerbate inequities in our society? How are we going to deal with a whole host of issues related to privacy?

Saey: I’m glad that you brought up equity and privacy, because those are some of the things that people are most concerned about right now. There are a lot of historically marginalized people who don’t want any part of genetic research because of the way their groups have been treated in the past. There’s been this history of colonialism. These groups say, if we’re going to do genetics on our people, then it should be our people doing it for us. What is NHGRI doing to build capacity in these communities so that they can do their own research and, maybe, if they decide they want to, share that with other people?

Green: I completely agree with the notion that if genomics is going to be a successful field, especially as we move this into medicine, we have got to make sure that we engage people from all different communities, all definitions of diversity, and make sure they benefit from it. We absolutely emphasize this point repeatedly in our 2020 strategic vision, so much so that the very first thing we did in 2021 was to release what we call an action agenda for enhancing the diversity of the genomics workforce.

Another experience we’ve had at NIH that I think is very illustrative of this: We recognized that we wanted African scientists to get more involved in doing genomics. And through a program called H3Africa, the Human Heredity and Health in Africa program, that the NIH and the Wellcome Trust funded, the philosophical mantra is to empower African scientists to do all the studies and build capacity there. It’s been a success by almost any metric. But it’s exactly what you said: We want them to do the studies, we want them to engage with their local communities. We’ll never build the trust if we just come in and say, “We’re going to do all of this.”

Saey: In terms of privacy, you’ve said a couple of times that you could have somebody’s genome completely sequenced, and then their doctor can use it. But don’t we get into a situation that could be like the movie Gattaca? Some people could be discriminated against if they don’t have their genetic flaws fixed? Are you somehow creating a class of lesser people and more perfect people who don’t have the genetic flaws that everybody else has?

Green: You just laid out several major ethical dilemmas, and they’re all valid, and we could spend hours talking about each of them. What I would say about our field is, we’ve recognized that everything we are doing is a two-edged sword. On the one edge of that sword are these incredible opportunities for improving the practice of medicine. On the other edge of that sword, as with many technologies, it could be used in ways that would be societally unacceptable. It’s a reason why the field has from the beginning always embraced and invested in ethical, legal and social implications research, or ELSI research, which has attempted to anticipate these concerns and try to provide an evidence base to build policies, and in some cases, laws.

We do have in the United States a major act called the Genetic Information Nondiscrimination Act, which offers some protection against genetic discrimination. We have laws and policies that protect people’s medical information.

We should recognize that genomics is just part of a bigger set of societal issues, as more and more intimate information about us is electronically available. Trust me, we can learn a lot about you if we just reviewed your Visa card purchases. We as a society have to recognize that, yes, genomic information has some unique attributes, but it’s not totally exceptional. We need to be part of a broader framework for protecting people so that we can benefit from these incredible opportunities.

We just need to make sure we don’t get too far out over our skis. Just because we can do something, doesn’t mean we should. We need to think about all the consequences. We should be constantly understanding what will society tolerate, what do people not want. We have some things that are going to be completely unacceptable, like doing genetic editing in unborn children. At this stage, we simply don’t think that’s a smart thing to do, we’re not ready to do it, the scientific community has condemned doing it (SN: 12/22/18 & 1/5/19, p. 20).

Saey: I do want to circle back, because when we were talking about these noncoding sequences, a lot of them help control how genes are used. That may not be so obvious if you just get this string of somebody’s DNA letters. Can you tell from that how those genes will be used? And how those things will be put together? Or is that something you cannot tell by looking at DNA?

Green: There’s no question that sometimes when you talk about genomics, and you talk about genetics, and you focus on the genes — you sometimes see the tree and you lose track of the forest. The forest is medical complexity and biological complexity. And for most things about ourselves, how tall we are, what we look like, and common diseases — hypertension, diabetes, Alzheimer’s, autism, et cetera — things are much more complicated than looking even for one gene. It’s multiple genes. And it’s almost always a greater choreography with our lifestyle, and our social experiences, and our exposures and everything from diet to exercise. There’s a lot more to health and disease than just our genes.

The grand challenge in many ways for the coming decade or two is doing these very large-scale studies where we have as much data as possible, not just genomic data, but lifestyle data and electronic health record data, and environmental data and physiological data. There are absolutely going to be patterns. And we’ve just got to find those patterns.

Saey: We’re almost out of time. It’s been wonderful talking with you. Did we miss anything?

Green: We missed all sorts of wonderful things, but you can only spend so much time walking down memory lane.

What I would say in closing are two things people need to remember: First of all, how incredibly exciting this field is, and how incredibly eager we are to build our tent with more and more people from all different disciplines. And we also want people of all different populations and ancestral groups from all parts of the world. It’s going to be so important to do that.

The reason we want all these people involved is, we just touched on so many things that we still don’t understand. We need creativity. And we don’t have a playbook. Just like those days where we were bewildered of how we were going to get the Human Genome Project really done, I don’t really know how we’re going to get complete end-to-end understanding of the human genome. But I know if we get creative people working on it, we’ll make incredible progress.

See the full article here .

five-ways-keep-your-child-safe-school-shootings

Please help promote STEM in your local schools.

Stem Education Coalition