From “The MIT Technology Review” : “Next up for CRISPR – Gene editing for the masses?”

From “The MIT Technology Review”

1.19.23
Jessica Hamzelou

Last year, Verve Therapeutics started the first human trial of a CRISPR treatment that could benefit most people—a signal that gene editing may be ready to go mainstream.

Stephanie Arnett/MITTR | Getty.

We know the basics of healthy living by now. A balanced diet, regular exercise, and stress reduction can help us avoid heart disease—the world’s biggest killer. But what if you could take a vaccine, too? And not a typical vaccine—one shot that would alter your DNA to provide lifelong protection?

That vision is not far off, researchers say. Advances in gene editing, and CRISPR technology in particular, may soon make it possible. In the early days, CRISPR was used to simply make cuts in DNA. Today, it’s being tested as a way to change existing genetic code, even by inserting all-new chunks of DNA or possibly entire genes into someone’s genome.

These new techniques mean CRISPR could potentially help treat many more conditions—not all of them genetic. In July 2022, for example, Verve Therapeutics launched a trial of a CRISPR-based therapy that alters genetic code to permanently lower cholesterol levels.

The first recipient—a volunteer in New Zealand—has an inherited risk for high cholesterol and already has heart disease. But Kiran Musunuru, cofounder and senior scientific advisor at Verve, thinks that the approach could help almost anyone.

The treatment works by permanently switching off a gene that codes for a protein called PCSK9, which seems to play a role in maintaining cholesterol levels in the blood.

“Even if you start with a normal cholesterol level, and you turn off PCSK9 and bring cholesterol levels even lower, that reduces the risk of having a heart attack,” says Musunuru. “It’s a general strategy that would work for anyone in the population.”

CRISPR’s evolution

While newer innovations are still being explored in lab dishes and research animals, CRISPR treatments have already entered human trials. It’s a staggering accomplishment when you consider that the technology was first used to edit the genomes of cells about 10 years ago. “It’s been a pretty quick journey to the clinic,” says Alexis Komor at the University of California-San Diego, who developed some of these newer forms of CRISPR gene editing.

Gene-editing treatments work by directly altering the DNA in a genome. The first generation of CRISPR technology essentially makes cuts in the DNA. Cells repair these cuts, and this process usually stops a harmful genetic mutation from having an effect.

Newer forms of CRISPR work in slightly different ways. Take base editing, which some describe as “CRISPR 2.0.” This technique targets the core building blocks of DNA, which are called bases.

There are four DNA bases: A, T, C, and G. Instead of cutting the DNA, CRISPR 2.0 machinery can convert one base letter into another. Base editing can swap a C for a T, or an A for a G. “It’s no longer acting like scissors, but more like a pencil and eraser,” says Musunuru.

In theory, base editing should be safer than the original form of CRISPR gene editing. Because the DNA is not being cut, there’s less chance that you’ll accidentally excise an important gene, or that the DNA will come back together in the wrong way.

Verve’s cholesterol-lowering treatment uses base editing, as do several other experimental therapies. A company called Beam Therapeutics, for example, is using the approach to create potential treatments for sickle-cell disease and other disorders.

And then there’s prime editing, or “CRISPR 3.0.” This technique allows scientists to replace bits of DNA or insert new chunks of genetic code. It has only been around for a few years and is still being explored in lab animals. But its potential is huge.

That’s because prime editing vastly expands the options. “CRISPR 1.0” and base editing are somewhat limited—you can only use them in situations where cutting DNA or changing a single letter would be useful. Prime editing could allow scientists to insert entirely new genes into a person’s genome.

That would open up many more genetic disorders as potential targets. If you want to correct a specific mutation that is beyond the reach of base editing, “prime editing is your only option,” says Musunuru.

If it works, it could be revolutionary. A hundred people with a disorder might have all kinds of genetic influences that made them vulnerable to it. But inserting a corrective gene could potentially cure all of them, says Musunuru. “If you can put in a fresh new working copy of the gene, it may not matter what mutation you have,” he says. “You’re putting in a working copy, and that’s good enough.”

Together, these new forms of CRISPR could dramatically broaden the scope of gene-editing treatments—making them potentially available to many more people, and for a much broader range of disorders. The target diseases don’t even have to be caused by genetic mutations. In fact, even some of the older CRISPR approaches could be used to target diseases that aren’t necessarily the result of a rogue gene. Verve’s treatment to permanently lower cholesterol is a first example of a CRISPR treatment that could benefit the majority of adults, according to Musnuru.

Genetic vaccinations

Verve’s approach involves swapping a base letter in the gene that codes for the PCSK9 protein. This disables the gene, so much less protein is made. Because the PCSK9 protein plays an important role in maintaining levels of LDL cholesterol—the type associated with clogged arteries—cholesterol levels drop too.

In experiments, when mice and monkeys were given the treatment, their blood cholesterol levels dropped by around 60 to 70% within a few days, says Musunuru. “And once it’s down, it stays down,” he adds. The company expects its first human clinical trial to run for a few years. If the trial is successful, the company will continue with larger trials. The treatment will have to be approved by the US Food and Drug Administration before it can be prescribed by doctors in the US. “It will be a while before any [CRISPR treatments] are actually approved for use,” says Musunuru.

But in the future, he says, we might be able to use the same approach to protect people from high blood pressure and diabetes.

Komor of UC-San Diego says a CRISPR-based treatment to prevent Alzheimer’s might also be desirable. But she cautions that editing the genomes of healthy people is ethically ambiguous and could be an unnecessary gamble for people who are otherwise well. “If I was given the opportunity to do editing of my liver cells to reduce cholesterol potentially in the future, I would probably say no,” she says. “I want to keep my genome as is, unless there’s a problem.”

Any new treatment has to be at least as safe as what is already available, says Tania Bubela, who studies the legal and ethical implications of new technologies at Simon Fraser University in Burnaby, British Columbia. Plenty of drugs have side effects. “The difference is that with a drug, you can … change the person’s medication,” says Bubela. “With a gene therapy, I can’t see how you would do that.”

The price, as well as the safety, of any gene-editing treatment will determine whether it can really help the masses, Bubela says: “I find it difficult to believe that a gene-based therapy like CRISPR will ever be either safer or more cost-effective than a very simple cholesterol pill.” But she accepts that these treatments could become cheaper, and that the “one-shot” approach might appeal to some.

There’s a good reason the first trials of CRISPR have focused on people with rare disorders who have few options, says Komor: “Those are the people most in need.” While broadening the applications of CRISPR is exciting, she says, “we have an ethical obligation to help those people before we help the general masses.”

See the full article here .

Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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

Please help promote STEM in your local schools.

Stem Education Coalition

The mission of “The MIT Technology Review” is to equip its audiences with the intelligence to understand a world shaped by technology.

From The University of Cambridge (UK) And The University of Copenhagen [Københavns Universitet](DK): “A new chapter in the history of evolution”

From The University of Cambridge (UK)

And

The University of Copenhagen [Københavns Universitet](DK)

12.7.22
Jo Tynan
Photography: Svend Funder
Art: Beth Zaiken

Acknowledgements:
Bianca De Sanctis
Kurt Kjær
Mikkel Pedersen
Eske Willerslev

Discovery of world’s oldest DNA breaks record by one million years.
We now know what the world looked like 2 million years ago.

Two-million-year-old DNA has been identified for the first time opening a new chapter in the history of evolution.

An artist’s impression of the Kap København formation two-million years ago in a time where the temperature was significantly warmer than northernmost Greenland today. Artist: Beth Zaiken/ http://www.bethzaiken.com

Microscopic fragments of environmental DNA were found in Ice Age sediment in northern Greenland. The fragments are one million years older than the previous record for DNA sampled from a Siberian mammoth bone. 

The ancient DNA has been used to map a two-million-year-old ecosystem which weathered extreme climate change. The results could help predict the long-term environmental toll of today’s global warming.

Main locality at the Kap København geological formation. At the bottom of the section the deep marine deposits are overlain by the coastal deposits of fine sandy material. The two people at the top are sampling for environmental DNA. Credit: Professor Svend Funder.

The discovery was made by a team of scientists led by Professor Eske Willerslev and Professor Kurt Kjær. Professor Willerslev is a Fellow of St John’s College, University of Cambridge and Director of the Lundbeck Foundation GeoGenetics Centre at the University of Copenhagen where Professor Kjær, a geology expert, is also based.  

The results of the 41 usable samples found hidden in clay and quartz are published today in Nature [below]. 

“A new chapter spanning one million extra years of history has finally been opened and for the first time we can look directly at the DNA of a past ecosystem that far back in time,” says Willerslev.

“DNA can degrade quickly but we’ve shown that under the right circumstances, we can now go back further in time than anyone could have dared imagine.”

“The ancient DNA samples were found buried deep in sediment that had built-up over 20,000 years,” says Kjær. “The sediment was eventually preserved in ice or permafrost and, crucially, not disturbed by humans for two million years.”

Close-up of organic material in the coastal deposits. The organic layers show traces of the rich plant flora and insect fauna that lived two million years ago at Kap København in North Greenland. Credit: Professor Svend Funder.

The incomplete samples, a few millionths of a millimetre long, were taken from the København Formation, a sediment deposit almost 100 metres thick tucked in the mouth of a fjord in the Arctic Ocean in Greenland’s northernmost point. The climate in Greenland at the time varied between Arctic and temperate and was between 10-17C warmer than Greenland is today. The sediment built up metre by metre in a shallow bay. 

Evidence of animals, plants and microorganisms including reindeer, hares, lemmings, birch and poplar trees were discovered. Researchers even found that Mastodon, an Ice Age mammal, roamed as far as Greenland before later becoming extinct. Previously it was thought the range of the elephant-like animals did not extend as far as Greenland from its known origins of North and Central America.

Detective work by 40 researchers from Denmark, the UK, France, Sweden, Norway, the USA and Germany, unlocked the secrets of the fragments of DNA. The process was painstaking – first they needed to establish whether there was DNA hidden in the clay and quartz, and if there was, could they successfully detach the DNA from the sediment to examine it? The answer, eventually, was yes. The researchers compared every single DNA fragment with extensive libraries of DNA collected from present-day animals, plants and microorganisms. A picture began to emerge of the DNA from trees, bushes, birds, animals and microorganisms.

Remains of wooden branches from the forest that grew at Kap København two million years ago. Credit: Professor Svend Funder.

Some of the DNA fragments were easy to classify as predecessors to present-day species, others could only be linked at genus level, and some originated from species impossible to place in the DNA libraries of animals, plants and microorganisms still living in the 21st century.

The two-million-year-old samples also help academics build a picture of a previously unknown stage in the evolution of the DNA of a range of species still in existence today.
________________________________________________________________________

“The Kap København ecosystem, which has no present-day equivalent, existed at considerably higher temperatures than we have today – and because, on the face of it, the climate seems to have been similar to the climate we expect on our planet in the future due to global warming,” says co-first author Assistant Professor Mikkel Pedersen of the Lundbeck Foundation GeoGenetics Centre.

“One of the key factors here is to what degree species will be able to adapt to the change in conditions arising from a significant increase in temperature. The data suggests that more species can evolve and adapt to wildly varying temperatures than previously thought. But, crucially, these results show they need time to do this. The speed of today’s global warming means organisms and species do not have that time so the climate emergency remains a huge threat to biodiversity and the world – extinction is on the horizon for some species including plants and trees.”

Professors Eske Willerslev and Kurt Kjær exposing fresh layers for sampling of sediments. Credit: Professor Svend Funder.

While reviewing the ancient DNA from the Kap København Formation, the researchers also found DNA from a wide range of microorganisms, including bacteria and fungi, which they are continuing to map. A detailed description of how the interaction – between animals, plants and single-cell organisms – within the former ecosystem at Greenland’s northernmost point worked biologically will be presented in a future research paper. 

It is now hoped that some of the ‘tricks’ of the two-million-year-old plant DNA discovered may be used to help make some endangered species more resistant to a warming climate. 

“It is possible that genetic engineering could mimic the strategy developed by plants and trees two million years ago to survive in a climate characterised by rising temperatures and prevent the extinction of some species, plants and trees,” says Kjær. “This is one of the reasons this scientific advance is so significant because it could reveal how to attempt to counteract the devastating impact of global warming.”

The findings from the Kap København Formation in Greenland have opened up a whole new period in DNA detection.

“DNA generally survives best in cold, dry conditions such as those that prevailed during most of the period since the material was deposited at Kap København,” says Willerslev. “Now that we have successfully extracted ancient DNA from clay and quartz, it may be possible that clay may have preserved ancient DNA in warm, humid environments in sites found in Africa.

“If we can begin to explore ancient DNA in clay grains from Africa, we may be able to gather ground-breaking information about the origin of many different species – perhaps even new knowledge about the first humans and their ancestors – the possibilities are endless.”

Science paper:
Nature
See the science paper for instructive material with images.

See the full article here .

Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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

Please help promote STEM in your local schools.

Stem Education Coalition

U Copenhagen campus

The University of Copenhagen [Københavns Universitet] (DK)] is a public research university in Copenhagen, Denmark. Founded in 1479, the University of Copenhagen is the second-oldest university in Scandinavia, and ranks as one of the top universities in the Nordic countries and Europe.

Its establishment sanctioned by Pope Sixtus IV, the University of Copenhagen was founded by Christian I of Denmark as a Catholic teaching institution with a predominantly theological focus. After 1537, it became a Lutheran seminary under King Christian III. Up until the 18th century, the university was primarily concerned with educating clergymen. Through various reforms in the 18th and 19th century, the University of Copenhagen was transformed into a modern, secular university, with science and the humanities replacing theology as the main subjects studied and taught.

The University of Copenhagen consists of six different faculties, with teaching taking place in its four distinct campuses, all situated in Copenhagen. The university operates 36 different departments and 122 separate research centres in Copenhagen, as well as a number of museums and botanical gardens in and outside the Danish capital. The University of Copenhagen also owns and operates multiple research stations around Denmark, with two additional ones located in Greenland. Additionally, The Faculty of Health and Medical Sciences and the public hospitals of the Capital and Zealand Region of Denmark constitute the conglomerate Copenhagen University Hospital.

A number of prominent scientific theories and schools of thought are namesakes of the University of Copenhagen. The famous Copenhagen Interpretation of quantum mechanics was conceived at the Niels Bohr Institute [Niels Bohr Institutet](DK), which is part of the university. The Department of Political Science birthed the Copenhagen School of Security Studies which is also named after the university. Others include the Copenhagen School of Theology and the Copenhagen School of Linguistics.

As of October 2020, 39 Nobel laureates and 1 Turing Award laureate have been affiliated with the University of Copenhagen as students, alumni or faculty. Alumni include one president of the United Nations General Assembly and at least 24 prime ministers of Denmark. The University of Copenhagen fosters entrepreneurship, and between 5 and 6 start-ups are founded by students, alumni or faculty members each week.

History

The university is a member of the International Alliance of Research Universities (IARU), along with University of Cambridge (UK), Yale University, The Australian National University (AU), and University of California, Berkeley, amongst others. The 2016 Academic Ranking of World Universities ranks the University of Copenhagen as the best university in Scandinavia and 30th in the world, the 2016-2017 Times Higher Education World University Rankings as 120th in the world, and the 2016-2017 QS World University Rankings as 68th in the world. The university has had 9 alumni become Nobel laureates and has produced one Turing Award recipient.

The University of Copenhagen was founded in 1479 and is the oldest university in Denmark. In 1474, Christian I of Denmark journeyed to Rome to visit Pope Sixtus IV, whom Christian I hoped to persuade into issuing a papal bull permitting the establishment of university in Denmark. Christian I failed to persuade the pope to issue the bull however and the king returned to Denmark the same year empty-handed. In 1475 Christian I’s wife Dorothea of Brandenburg Queen of Denmark made the same journey to Rome as her husband did a year before. Unlike Christian I Dorothea managed to persuade Pope Sixtus IV into issuing the papal bull. On the 19th of June, 1475 Pope Sixtus IV issued an official papal bull permitting the establishment of what was to become the University of Copenhagen.

On the 4th of October, 1478 Christian I of Denmark issued a royal decree by which he officially established the University of Copenhagen. In this decree Christian I set down the rules and laws governing the university. The royal decree elected magistar Peder Albertsen as vice chancellor of the university and the task was his to employ various learned scholars at the new university and thereby establish its first four faculties: theology; law; medicine; and philosophy. The royal decree made the University of Copenhagen enjoy royal patronage from its very beginning. Furthermore, the university was explicitly established as an autonomous institution giving it a great degree of juridical freedom. As such the University of Copenhagen was to be administered without royal interference and it was not subject to the usual laws governing the Danish people.

The University of Copenhagen was closed by the Church in 1531 to stop the spread of Protestantism and re-established in 1537 by King Christian III after the Lutheran Reformation and transformed into an evangelical-Lutheran seminary. Between 1675 and 1788 the university introduced the concept of degree examinations. An examination for theology was added in 1675 followed by law in 1736. By 1788 all faculties required an examination before they would issue a degree.

In 1807 the British Bombardment of Copenhagen destroyed most of the university’s buildings. By 1836 however the new main building of the university was inaugurated amid extensive building that continued until the end of the century. The University Library (now a part of the Royal Library); the Zoological Museum; the Geological Museum; the Botanic Garden with greenhouses; and the Technical College were also established during this period.

Between 1842 and 1850 the faculties at the university were restructured. Starting in 1842 the University Faculty of Medicine and the Academy of Surgeons merged to form the Faculty of Medical Science while in 1848 the Faculty of Law was reorganised and became the Faculty of Jurisprudence and Political Science. In 1850 the Faculty of Mathematics and Science was separated from the Faculty of Philosophy. In 1845 and 1862 Copenhagen co-hosted nordic student meetings with Lund University [Lunds universitet] (SE).

The first female student was enrolled at the university in 1877. The university underwent explosive growth between 1960 and 1980. The number of students rose from around 6,000 in 1960 to about 26,000 in 1980 with a correspondingly large growth in the number of employees. Buildings built during this time period include the new Zoological Museum; the Hans Christian Ørsted and August Krogh Institutes; the campus centre on Amager Island; and the Panum Institute.

The new university statute instituted in 1970 involved democratisation of the management of the university. It was modified in 1973 and subsequently applied to all higher education institutions in Denmark. The democratisation was later reversed with the 2003 university reforms. Further change in the structure of the university from 1990 to 1993 made a Bachelor’s degree programme mandatory in virtually all subjects.

The University of Cambridge (UK) [legally The Chancellor, Masters, and Scholars of the University of Cambridge] is a collegiate public research university in Cambridge, England. Founded in 1209 Cambridge is the second-oldest university in the English-speaking world and the world’s fourth-oldest surviving university. It grew out of an association of scholars who left the University of Oxford (UK) after a dispute with townsfolk. The two ancient universities share many common features and are often jointly referred to as “Oxbridge”.

Cambridge is formed from a variety of institutions which include 31 semi-autonomous constituent colleges and over 150 academic departments, faculties and other institutions organized into six schools. All the colleges are self-governing institutions within the university, each controlling its own membership and with its own internal structure and activities. All students are members of a college. Cambridge does not have a main campus and its colleges and central facilities are scattered throughout the city. Undergraduate teaching at Cambridge is organized around weekly small-group supervisions in the colleges – a feature unique to the Oxbridge system. These are complemented by classes, lectures, seminars, laboratory work and occasionally further supervisions provided by the central university faculties and departments. Postgraduate teaching is provided predominantly centrally.

Cambridge University Press a department of the university is the oldest university press in the world and currently the second largest university press in the world. Cambridge Assessment also a department of the university is one of the world’s leading examining bodies and provides assessment to over eight million learners globally every year. The university also operates eight cultural and scientific museums, including the Fitzwilliam Museum, as well as a botanic garden. Cambridge’s libraries – of which there are 116 – hold a total of around 16 million books, around nine million of which are in Cambridge University Library, a legal deposit library. The university is home to – but independent of – the Cambridge Union – the world’s oldest debating society. The university is closely linked to the development of the high-tech business cluster known as “Silicon Fe”. It is the central member of Cambridge University Health Partners, an academic health science centre based around the Cambridge Biomedical Campus.

By both endowment size and consolidated assets Cambridge is the wealthiest university in the United Kingdom. In the fiscal year ending 31 July 2019, the central university – excluding colleges – had a total income of £2.192 billion of which £592.4 million was from research grants and contracts. At the end of the same financial year the central university and colleges together possessed a combined endowment of over £7.1 billion and overall consolidated net assets (excluding “immaterial” historical assets) of over £12.5 billion. It is a member of numerous associations and forms part of the ‘golden triangle’ of English universities.

Cambridge has educated many notable alumni including eminent mathematicians; scientists; politicians; lawyers; philosophers; writers; actors; monarchs and other heads of state. As of October 2020, 121 Nobel laureates; 11 Fields Medalists; 7 Turing Award winners; and 14 British prime ministers have been affiliated with Cambridge as students; alumni; faculty or research staff. University alumni have won 194 Olympic medals.

History

By the late 12th century, the Cambridge area already had a scholarly and ecclesiastical reputation due to monks from the nearby bishopric church of Ely. However, it was an incident at Oxford which is most likely to have led to the establishment of the university: three Oxford scholars were hanged by the town authorities for the death of a woman without consulting the ecclesiastical authorities who would normally take precedence (and pardon the scholars) in such a case; but were at that time in conflict with King John. Fearing more violence from the townsfolk scholars from the University of Oxford started to move away to cities such as Paris; Reading; and Cambridge. Subsequently enough scholars remained in Cambridge to form the nucleus of a new university when it had become safe enough for academia to resume at Oxford. In order to claim precedence, it is common for Cambridge to trace its founding to the 1231 charter from Henry III granting it the right to discipline its own members (ius non-trahi extra) and an exemption from some taxes; Oxford was not granted similar rights until 1248.

A bull in 1233 from Pope Gregory IX gave graduates from Cambridge the right to teach “everywhere in Christendom”. After Cambridge was described as a studium generale in a letter from Pope Nicholas IV in 1290 and confirmed as such in a bull by Pope John XXII in 1318 it became common for researchers from other European medieval universities to visit Cambridge to study or to give lecture courses.

Foundation of the colleges

The colleges at the University of Cambridge were originally an incidental feature of the system. No college is as old as the university itself. The colleges were endowed fellowships of scholars. There were also institutions without endowments called hostels. The hostels were gradually absorbed by the colleges over the centuries; but they have left some traces, such as the name of Garret Hostel Lane.

Hugh Balsham, Bishop of Ely, founded Peterhouse – Cambridge’s first college in 1284. Many colleges were founded during the 14th and 15th centuries but colleges continued to be established until modern times. There was a gap of 204 years between the founding of Sidney Sussex in 1596 and that of Downing in 1800. The most recently established college is Robinson built in the late 1970s. However, Homerton College only achieved full university college status in March 2010 making it the newest full college (it was previously an “Approved Society” affiliated with the university).

In medieval times many colleges were founded so that their members would pray for the souls of the founders and were often associated with chapels or abbeys. The colleges’ focus changed in 1536 with the Dissolution of the Monasteries. Henry VIII ordered the university to disband its Faculty of Canon Law and to stop teaching “scholastic philosophy”. In response, colleges changed their curricula away from canon law and towards the classics; the Bible; and mathematics.

Nearly a century later the university was at the centre of a Protestant schism. Many nobles, intellectuals and even commoners saw the ways of the Church of England as too similar to the Catholic Church and felt that it was used by the Crown to usurp the rightful powers of the counties. East Anglia was the centre of what became the Puritan movement. In Cambridge the movement was particularly strong at Emmanuel; St Catharine’s Hall; Sidney Sussex; and Christ’s College. They produced many “non-conformist” graduates who, greatly influenced by social position or preaching left for New England and especially the Massachusetts Bay Colony during the Great Migration decade of the 1630s. Oliver Cromwell, Parliamentary commander during the English Civil War and head of the English Commonwealth (1649–1660), attended Sidney Sussex.

Modern period

After the Cambridge University Act formalized the organizational structure of the university the study of many new subjects was introduced e.g. theology, history and modern languages. Resources necessary for new courses in the arts architecture and archaeology were donated by Viscount Fitzwilliam of Trinity College who also founded the Fitzwilliam Museum. In 1847 Prince Albert was elected Chancellor of the University of Cambridge after a close contest with the Earl of Powis. Albert used his position as Chancellor to campaign successfully for reformed and more modern university curricula, expanding the subjects taught beyond the traditional mathematics and classics to include modern history and the natural sciences. Between 1896 and 1902 Downing College sold part of its land to build the Downing Site with new scientific laboratories for anatomy, genetics, and Earth sciences. During the same period the New Museums Site was erected including the Cavendish Laboratory which has since moved to the West Cambridge Site and other departments for chemistry and medicine.

The University of Cambridge began to award PhD degrees in the first third of the 20th century. The first Cambridge PhD in mathematics was awarded in 1924.

In the First World War 13,878 members of the university served and 2,470 were killed. Teaching and the fees it earned came almost to a stop and severe financial difficulties followed. As a consequence, the university first received systematic state support in 1919 and a Royal Commission appointed in 1920 recommended that the university (but not the colleges) should receive an annual grant. Following the Second World War the university saw a rapid expansion of student numbers and available places; this was partly due to the success and popularity gained by many Cambridge scientists.

From The School of Mechanical and Aerospace Engineering In The Jacobs School of Engineering At The University of California-San Diego: “Stresses and Hydrodynamics – Scientists Uncover New Organizing Principles of the Genome”

From The School of Mechanical and Aerospace Engineering

In

The Jacobs School of Engineering

At

The University of California-San Diego

12.23.22
By James Devitt

Media Contact:
Katherine Connor
khconnor@ucsd.edu

The cell nucleus is filled with chromosomes, which are illustrated by different colors in this depiction. Its chromosome arrangements are affected by active forces on the genome and their hydrodynamic interactions. Image by Achal Mahajan, UC San Diego.

A team of scientists including mechanical engineers at the University of California-San Diego has uncovered the physical principles—a series of forces and hydrodynamic flows—that help ensure the proper functioning of life’s blueprint. Its discovery provides new insights into the genome while potentially offering a new means to spot genomic aberrations linked to developmental disorders and human diseases.

“The way in which the genome is organized and packed inside the nucleus directly affects its biological function, yet the physical principles behind this organization are far from understood,” explains Alexandra Zidovska, an associate professor in New York University’s Department of Physics and an author of the paper, published in the journal Physical Review X [below] on Dec. 23, 2022. “Our results provide fundamental insights into the biophysical origins of the organization of the genome inside the cell nucleus.”  

“Such knowledge is crucial for understanding the genome’s function,” adds David Saintillan, a professor at UC San Diego’s Department of Mechanical and Aerospace Engineering and an author of the paper.

“Our findings show the key role of physics in the genome’s organization and hence its function,” observes Michael Shelley, a professor at NYU’s Courant Institute of Mathematical Sciences, a researcher at the Flatiron Institute, and an author of the paper.

The team, which also included Achal Mahajan, a UC San Diego doctoral student at the time of the work and first author of the paper, and Wen Yan, formerly of the Flatiron Institute’s Center for Computational Biology, focused on the role of the nucleoplasm—the fluid in which the genome is immersed—and the forces that drive its organization.

Specifically, the scientists examined the forces applied on chromosomal material, or chromatin, by enzymes at work in a cell’s nucleus. Here, these forces initiate processes, such as transcription, and act in ways that affect the spatial arrangement of the chromatin. 

This organization affects biological function. But despite the crucial role of this process in conveying genetic information, the physics underlying it are opaque.

In pursuing a greater understanding of this dynamic, the scientists focused on the genome’s compartmentalization into its primary parts, euchromatin and heterochromatin. Euchromatin contains predominantly actively transcribing genes, which drive expression; heterochromatin contains genes that are silenced—and therefore not expressed in the cell.

To capture this, they created a computer modeling system that replicated this process through a series of simulations. In their model nucleus, 23 chromatin fibers—the number of chromosomes in the human genome—were modeled as floppy chains and stuffed into a fluid-filled sphere. Each chain was divided up into active regions, or euchromatin, and passive heterochromatic regions. 

They found that when active forces act on the chromatin fiber, they generate flows in the fluid around them, which in turn affect the motion and positioning of the surrounding chromatin. These forces push on the euchromatic parts and drive flows that cause a major spatial rearrangement of the genome, notably leading to the formation of heterochromatin compartments.

“The euchromatic, or active, parts push the heterochromatic, or inactive, parts out of their way and bunch them together,” explains Zidovska. “This is how the cell effectively stores inactive genes.

“This is crucial for our health—if this process goes awry, the organism doesn’t form properly and potentially leads to developmental disorders and other afflictions, such as the development of cancer cells.”

An image and a video, along with captions and credits, depicting this process may be accessed from Google Drive [I checked it. Really cool. Try it out.] 

Science paper:
Physical Review X
If the reader has the proper credentials, See the science paper for instructive material with images.

This research was supported by grants from the National Science Foundation (CMMI-1762506, DMS-2153432, CMMI-1762566, DMS-2153520, DMR-2004469, CAREER PHY-1554880 and PHY-2210541).

See the full article here .

Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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

Please help promote STEM in your local schools.

Stem Education Coalition

The University of California San Diego School of Mechanical and Aerospace Engineering

In

The Jacobs School of Engineering
Innovation Happens Here

The University of California-San Diego Jacobs School of Engineering is a premier research school set apart by our entrepreneurial culture and integrative engineering approach.

The Jacobs School’s Mission:

Educate Tomorrow’s Technology Leaders
Conduct Leading Edge Research and Drive Innovation
Transfer Discoveries for the Benefit of Society

The Jacobs School’s Values:

Engineering for the global good
Exponential impact through entrepreneurism
Collaboration to enrich relevance
Our education models focus on deep and broad engineering fundamentals, enhanced by real-world design and research, often in partnership with industry. Through our Team Internship Program and GlobalTeams in Engineering Service program, for example, we encourage students to develop their communications and leadership skills while working in the kind of multi-disciplinary team environment experienced by real-world engineers.

We are home to exciting research centers, such as the San Diego Supercomputer Center, a national resource for data-intensive computing; our Powell Structural Research Laboratories, the largest and most active in the world for full-scale structural testing; and the Qualcomm Institute, which is the UC San Diego division of the California Institute for Telecommunications and Information Technology (Calit2), which is forging new ground in multi-disciplinary applications for information technology.

Located at the hub of San Diego’s thriving information technology, biotechnology, clean technology, and nanotechnology sectors, the Jacobs School proactively seeks corporate partners to collaborate with us in research, education and innovation.

The University of California-San Diego

The University of California- San Diego, is a public research university located in the La Jolla area of San Diego, California, in the United States. The university occupies 2,141 acres (866 ha) near the coast of the Pacific Ocean with the main campus resting on approximately 1,152 acres (466 ha). Established in 1960 near the pre-existing Scripps Institution of Oceanography, University of California, San Diego is the seventh oldest of the 10 University of California campuses and offers over 200 undergraduate and graduate degree programs, enrolling about 22,700 undergraduate and 6,300 graduate students. The University of California-San Diego is one of America’s “Public Ivy” universities, which recognizes top public research universities in the United States. The University of California-San Diego was ranked 8th among public universities and 37th among all universities in the United States, and rated the 18th Top World University by U.S. News & World Report’s 2015 rankings.

The University of California-San Diego is organized into seven undergraduate residential colleges (Revelle; John Muir; Thurgood Marshall; Earl Warren; Eleanor Roosevelt; Sixth; and Seventh), four academic divisions (Arts and Humanities; Biological Sciences; Physical Sciences; and Social Sciences), and seven graduate and professional schools (Jacobs School of Engineering; Rady School of Management; Scripps Institution of Oceanography; School of Global Policy and Strategy; School of Medicine; Skaggs School of Pharmacy and Pharmaceutical Sciences; and the newly established Wertheim School of Public Health and Human Longevity Science). University of California-San Diego Health, the region’s only academic health system, provides patient care; conducts medical research; and educates future health care professionals at the University of California-San Diego Medical Center, Hillcrest; Jacobs Medical Center; Moores Cancer Center; Sulpizio Cardiovascular Center; Shiley Eye Institute; Institute for Genomic Medicine; Koman Family Outpatient Pavilion and various express care and urgent care clinics throughout San Diego.

The university operates 19 organized research units (ORUs), including the Center for Energy Research; Qualcomm Institute (a branch of the California Institute for Telecommunications and Information Technology); San Diego Supercomputer Center; and the Kavli Institute for Brain and Mind, as well as eight School of Medicine research units, six research centers at Scripps Institution of Oceanography and two multi-campus initiatives, including the Institute on Global Conflict and Cooperation. The University of California-San Diego is also closely affiliated with several regional research centers, such as the Salk Institute; the Sanford Burnham Prebys Medical Discovery Institute; the Sanford Consortium for Regenerative Medicine; and the Scripps Research Institute. It is classified among “R1: Doctoral Universities – Very high research activity”. According to the National Science Foundation, UC San Diego spent $1.265 billion on research and development in fiscal year 2018, ranking it 7th in the nation.

The University of California-San Diego is considered one of the country’s “Public Ivies”. As of February 2021, The University of California-San Diego faculty, researchers and alumni have won 27 Nobel Prizes and three Fields Medals, eight National Medals of Science, eight MacArthur Fellowships, and three Pulitzer Prizes. Additionally, of the current faculty, 29 have been elected to the National Academy of Engineering, 70 to the National Academy of Sciences, 45 to the National Academy of Medicine and 110 to the American Academy of Arts and Sciences.

History

When the Regents of the University of California originally authorized the San Diego campus in 1956, it was planned to be a graduate and research institution, providing instruction in the sciences, mathematics, and engineering. Local citizens supported the idea, voting the same year to transfer to the university 59 acres (24 ha) of mesa land on the coast near the preexisting Scripps Institution of Oceanography. The Regents requested an additional gift of 550 acres (220 ha) of undeveloped mesa land northeast of Scripps, as well as 500 acres (200 ha) on the former site of Camp Matthews from the federal government, but Roger Revelle, then director of Scripps Institution and main advocate for establishing the new campus, jeopardized the site selection by exposing the La Jolla community’s exclusive real estate business practices, which were antagonistic to minority racial and religious groups. This outraged local conservatives, as well as Regent Edwin W. Pauley.

University of California President Clark Kerr satisfied San Diego city donors by changing the proposed name from University of California, La Jolla, to University of California-San Diego. The city voted in agreement to its part in 1958, and the University of California approved construction of the new campus in 1960. Because of the clash with Pauley, Revelle was not made chancellor. Herbert York, first director of DOE’s Lawrence Livermore National Laboratory, was designated instead. York planned the main campus according to the “Oxbridge” model, relying on many of Revelle’s ideas.

According to Kerr, “San Diego always asked for the best,” though this created much friction throughout the University of California system, including with Kerr himself, because University of California-San Diego often seemed to be “asking for too much and too fast.” Kerr attributed University of California-San Diego’s “special personality” to Scripps, which for over five decades had been the most isolated University of California unit in every sense: geographically, financially, and institutionally. It was a great shock to the Scripps community to learn that Scripps was now expected to become the nucleus of a new University of California campus and would now be the object of far more attention from both the university administration in Berkeley and the state government in Sacramento.

The University of California-San Diego was the first general campus of the University of California to be designed “from the top down” in terms of research emphasis. Local leaders disagreed on whether the new school should be a technical research institute or a more broadly based school that included undergraduates as well. John Jay Hopkins of General Dynamics Corporation pledged one million dollars for the former while the City Council offered free land for the latter. The original authorization for the University of California-San Diego campus given by the University of California Regents in 1956 approved a “graduate program in science and technology” that included undergraduate programs, a compromise that won both the support of General Dynamics and the city voters’ approval.

Nobel laureate Harold Urey, a physicist from the University of Chicago, and Hans Suess, who had published the first paper on the greenhouse effect with Revelle in the previous year, were early recruits to the faculty in 1958. Maria Goeppert-Mayer, later the second female Nobel laureate in physics, was appointed professor of physics in 1960. The graduate division of the school opened in 1960 with 20 faculty in residence, with instruction offered in the fields of physics, biology, chemistry, and earth science. Before the main campus completed construction, classes were held in the Scripps Institution of Oceanography.

By 1963, new facilities on the mesa had been finished for the School of Science and Engineering, and new buildings were under construction for Social Sciences and Humanities. Ten additional faculty in those disciplines were hired, and the whole site was designated the First College, later renamed after Roger Revelle, of the new campus. York resigned as chancellor that year and was replaced by John Semple Galbraith. The undergraduate program accepted its first class of 181 freshman at Revelle College in 1964. Second College was founded in 1964, on the land deeded by the federal government, and named after environmentalist John Muir two years later. The University of California-San Diego School of Medicine also accepted its first students in 1966.

Political theorist Herbert Marcuse joined the faculty in 1965. A champion of the New Left, he reportedly was the first protester to occupy the administration building in a demonstration organized by his student, political activist Angela Davis. The American Legion offered to buy out the remainder of Marcuse’s contract for $20,000; the Regents censured Chancellor William J. McGill for defending Marcuse on the basis of academic freedom, but further action was averted after local leaders expressed support for Marcuse. Further student unrest was felt at the university, as the United States increased its involvement in the Vietnam War during the mid-1960s, when a student raised a Viet Minh flag over the campus. Protests escalated as the war continued and were only exacerbated after the National Guard fired on student protesters at Kent State University in 1970. Over 200 students occupied Urey Hall, with one student setting himself on fire in protest of the war.

Early research activity and faculty quality, notably in the sciences, was integral to shaping the focus and culture of the university. Even before The University of California-San Diego had its own campus, faculty recruits had already made significant research breakthroughs, such as the Keeling Curve, a graph that plots rapidly increasing carbon dioxide levels in the atmosphere and was the first significant evidence for global climate change; the Kohn–Sham equations, used to investigate particular atoms and molecules in quantum chemistry; and the Miller–Urey experiment, which gave birth to the field of prebiotic chemistry.

Engineering, particularly computer science, became an important part of the university’s academics as it matured. University researchers helped develop University of California-San Diego Pascal, an early machine-independent programming language that later heavily influenced Java; the National Science Foundation Network, a precursor to the Internet; and the Network News Transfer Protocol during the late 1970s to 1980s. In economics, the methods for analyzing economic time series with time-varying volatility (ARCH), and with common trends (cointegration) were developed. The University of California-San Diego maintained its research intense character after its founding, racking up 25 Nobel Laureates affiliated within 50 years of history; a rate of five per decade.

Under Richard C. Atkinson’s leadership as chancellor from 1980 to 1995, the university strengthened its ties with the city of San Diego by encouraging technology transfer with developing companies, transforming San Diego into a world leader in technology-based industries. He oversaw a rapid expansion of the School of Engineering, later renamed after Qualcomm founder Irwin M. Jacobs, with the construction of the San Diego Supercomputer Center and establishment of the computer science, electrical engineering, and bioengineering departments. Private donations increased from $15 million to nearly $50 million annually, faculty expanded by nearly 50%, and enrollment doubled to about 18,000 students during his administration. By the end of his chancellorship, the quality of The University of California-San Diego graduate programs was ranked 10th in the nation by the National Research Council.

The university continued to undergo further expansion during the first decade of the new millennium with the establishment and construction of two new professional schools — the Skaggs School of Pharmacy and Rady School of Management—and the California Institute for Telecommunications and Information Technology, a research institute run jointly with University of California Irvine. The University of California-San Diego also reached two financial milestones during this time, becoming the first university in the western region to raise over $1 billion in its eight-year fundraising campaign in 2007 and also obtaining an additional $1 billion through research contracts and grants in a single fiscal year for the first time in 2010. Despite this, due to the California budget crisis, the university loaned $40 million against its own assets in 2009 to offset a significant reduction in state educational appropriations. The salary of Pradeep Khosla, who became chancellor in 2012, has been the subject of controversy amidst continued budget cuts and tuition increases.

On November 27, 2017, the university announced it would leave its longtime athletic home of the California Collegiate Athletic Association, an NCAA Division II league, to begin a transition to Division I in 2020. At that time, it will join the Big West Conference, already home to four other UC campuses (Davis, Irvine, Riverside, Santa Barbara). The transition period will run through the 2023–24 school year. The university prepares to transition to NCAA Division I competition on July 1, 2020.

Research

Applied Physics and Mathematics

The Nature Index lists The University of California-San Diego as 6th in the United States for research output by article count in 2019. In 2017, The University of California-San Diego spent $1.13 billion on research, the 7th highest expenditure among academic institutions in the U.S. The university operates several organized research units, including the Center for Astrophysics and Space Sciences (CASS), the Center for Drug Discovery Innovation, and the Institute for Neural Computation. The University of California-San Diego also maintains close ties to the nearby Scripps Research Institute and Salk Institute for Biological Studies. In 1977, The University of California-San Diego developed and released the University of California-San Diego Pascal programming language. The university was designated as one of the original national Alzheimer’s disease research centers in 1984 by the National Institute on Aging. In 2018, The University of California-San Diego received $10.5 million from the DOE National Nuclear Security Administration to establish the Center for Matters under Extreme Pressure (CMEC).

The university founded the San Diego Supercomputer Center (SDSC) in 1985, which provides high performance computing for research in various scientific disciplines. In 2000, The University of California-San Diego partnered with The University of California-Irvine to create the Qualcomm Institute – University of California-San Diego, which integrates research in photonics, nanotechnology, and wireless telecommunication to develop solutions to problems in energy, health, and the environment.

The University of California-San Diego also operates the Scripps Institution of Oceanography, one of the largest centers of research in earth science in the world, which predates the university itself. Together, SDSC and SIO, along with funding partner universities California Institute of Technology, San Diego State University, and The University of California-Santa Barbara, manage the High Performance Wireless Research and Education Network.

From The North Carolina State University: “In Ironic Twist CRISPR System Used to Befuddle Bacteria”

From The North Carolina State University

11.7.22 [Just found this.]

Mick Kulikowski

Rodolphe Barrangou
rbarran@ncsu.edu

Mick Kulikowski
mick_kulikowski@ncsu.edu
919.218.5937

Model grass Brachypodium distachyon plant grown on liquid media. Photo courtesy of Marta Torres, m-CAFEs postdoctoral researcher, Deutschbauer lab, Environmental Genomics and Systems Biology “© The Regents of the University of California, The DOE’s Lawrence Berkeley National Laboratory.”

Call it a CRISPR conundrum.

Bacteria use CRISPR-Cas systems as adaptive immune systems to withstand attacks from enemies like viruses. These systems have been adapted by scientists to remove or cut and replace specific genetic code sequences in a variety of organisms.

But in a new study, North Carolina State University researchers show that viruses engineered with a CRISPR-Cas system can thwart bacterial defenses and make selective changes to a targeted bacterium – even when other bacteria are in close proximity.

“Viruses are very good at delivering payloads. Here, we use a bacterial virus, a bacteriophage, to deliver CRISPR to bacteria, which is ironic because bacteria normally use CRISPR to kill viruses,” said Rodolphe Barrangou, the Todd R. Klaenhammer Distinguished Professor of Food, Bioprocessing and Nutrition Sciences at NC State and corresponding author of a paper describing the research published today in PNAS [below]. “The virus in this case targets E. coli by delivering DNA to it. It’s like using a virus as a syringe.”

Fig. 1.

Cas9-mediated phage engineering of T7 and λ. (A) Vector map of the generic construct used to engineer both T7 and λ. This construct contains the components necessary for Cas9-based targeting of nonedited phages, as well as a repair template, which is inserted into the EagI site. (B) The site of mCherry insertion in the T7 genome. (C) The insertion site of the gfp and gmR genes into the λ genome. Three nonessential genes (ea47, ea31, and ea59) from the b region are replaced through homologous recombination. (D) Microscope images from time points from λ::gfp:gmR infection of E. coli c600. Light microscope: Upper row. Fluorescence: Lower row. (E) Fluorescent growth curve generated from the infection of c600 with λ::gfp:gmR and wild-type λ. Shaded regions adjacent to each line indicate SE.

Fig. 2.

λ engineered to contain a CBE. (A) The insertion site of the CBE as well as the gmR sequence into the λ genome. Four genes from λ’s b region are replaced through homologous recombination: Orf-314, ea47, ea31, and ea59. (B) Vector map of pTRK1288, the engineering plasmid used to generate λ::CBE. (C) Long-read nanopore sequencing coverage generated from λ::CBE integration into the c600 genome.

The NC State researchers deployed two different engineered bacteriophages to deliver CRISPR-Cas payloads for targeted editing of E. coli, first in a test tube and then within a synthetic soil environment created to mimic soil – a complex environment that can harbor many types of bacteria.

Both the engineered bacteriophages, called T7 and lambda, successfully found and then delivered payloads to the E. coli host on the lab bench. These payloads expressed bacterial florescent genes and manipulated the bacterium’s resistance to an antibiotic.

The researchers then used lambda to deliver a so-called cytosine base editor to the E. coli host. Rather than CRISPR’s sometimes harsh cleaving of DNA sequences, this base editor changed just one letter of E. coli’s DNA, showing the sensitivity and precision of the system. These changes inactivated certain bacterial genes without making other changes to E. coli.

“We used a base editor here as a kind of programmable on-off switch for genes in E. coli. Using a system like this, we can make highly precise single-letter changes to the genome without the double-strand DNA breakage commonly associated with CRISPR-Cas targeting,” said Matthew Nethery, a former NC State Ph.D. student and lead author of the study.

Finally, the researchers demonstrated on-site editing through the use of a fabricated ecosystem (EcoFAB) loaded with a synthetic soil medium of sand and quartz, along with liquid, to mimic a soil environment. The researchers also included three different types of bacteria to test if the phage could specifically locate E. coli within the system.

“In a lab, scientists can oversimplify things,” Barrangou said. “It’s preferable to model environments, so rather than soup in a test tube, we wanted to examine real-life environments.”

The researchers inserted lambda into the fabricated ecosystem. It showed good efficiency in finding E. coli and making the targeted genetic changes.

“This technology is going to enable our team and others to discover the genetic basis of key bacterial interactions with plants and other microbes within highly controlled laboratory environments such as EcoFABs,” said Trent Northen, a scientist at the DOE’s Lawrence Berkeley National Laboratory who collaborates with Barrangou.

“We see this as a mechanism to aid the microbiome. We can make a change to a particular bacterium and the rest of the microbiome remains unscathed,” Barrangou said. “This is a proof of concept that could be employed in any complex microbial community, which could translate into better plant health and better gastrointestinal tract health – environments of importance to food and health.

“Ultimately this study represents the next chapter of CRISPR delivery – using viruses to deliver CRISPR machinery in a complex environment.”

The researchers plan to further this work by testing the phage CRISPR technique with other soil-associated bacteria. Importantly, this illustrates how soil microbial communities can be manipulated to control the composition and function of bacteria associated with plants in fabricated ecosystems to understand how to enhance plant growth and promote plant health, which is of broad interest for sustainable agriculture.

Funding was provided by m-CAFEs Microbial Community Analysis & Functional Evaluation in Soils, a Science Focus Area led by The DOE’s Lawrence Berkeley National Laboratory and supported by the U.S. Dept. of Energy under contract no. DE-AC02-05CH11231, with collaborative efforts including UC Berkeley and the Innovative Genomics Institute. Co-authors of the paper include Nethery, former NC State post-doctoral researcher Claudio Hidalgo-Cantabrana and NC State graduate student Avery Roberts.

Science paper:
PNAS
See the science paper for instructive material with more images.

See the full article here .

Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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

Please help promote STEM in your local schools.

Stem Education Coalition

The North Carolina State University was founded with a purpose: to create economic, societal and intellectual prosperity for the people of North Carolina and the country. We began as a land-grant institution teaching the agricultural and mechanical arts. Today, we’re a pre-eminent research enterprise that excels in science, technology, engineering, math, design, the humanities and social sciences, textiles and veterinary medicine.

North Carolina State University students, faculty and staff take problems in hand and work with industry, government and nonprofit partners to solve them. Our 34,000-plus high-performing students apply what they learn in the real world by conducting research, working in internships and co-ops, and performing acts of world-changing service. That experiential education ensures they leave here ready to lead the workforce, confident in the knowledge that NC State consistently rates as one of the best values in higher education.

North Carolina State University is a public land-grant research university in Raleigh, North Carolina. Founded in 1887 and part of the University of North Carolina system, it is the largest university in the Carolinas. The university forms one of the corners of the “Research Triangle” together with Duke University in Durham and the University of North Carolina-Chapel Hill. It is classified among “R1: Doctoral Universities – Very high research activity”.

The North Carolina General Assembly established the North Carolina College of Agriculture and Mechanic Arts, now North Carolina State University, on March 7, 1887, originally as a land-grant college. The college underwent several name changes and officially became North Carolina State University at Raleigh in 1965, and by longstanding convention, the “at Raleigh” portion was omitted. Today, North Carolina State University has an enrollment of more than 35,000 students, making it among the largest in the country. North Carolina State University has historical strengths in engineering, statistics, agriculture, life sciences, textiles, and design and offers bachelor’s degrees in 106 fields of study. The graduate school offers master’s degrees in 104 fields, doctoral degrees in 61 fields, and a Doctor of Veterinary Medicine.

North Carolina State University athletic teams are known as the Wolfpack. The name was adopted in 1922 when a disgruntled fan described the behavior of the student body at athletic events as being “like a wolf pack.” They compete in NCAA Division I and have won eight national championships: two NCAA championships, two AIAW championships, and four titles under other sanctioning bodies.

The North Carolina General Assembly founded North Carolina State University on March 7, 1887 as a land-grant college under the name “North Carolina College of Agriculture and Mechanic Arts,” or “North Carolina A&M” for short. In the segregated system, it was open only to white students. As a land-grant college, North Carolina A&M would provide a liberal and practical education while focusing on military tactics, agriculture, and the mechanical arts without excluding classical studies. Since its founding, the university has maintained these objectives while building on them. After opening in 1889, North Carolina A&M saw its enrollment fluctuate and its mandate expand. In 1917, it changed its name to “North Carolina State College of Agriculture and Engineering”—or “North Carolina State” for short. During the Great Depression, the North Carolina state government, under Governor O. Max Gardner, administratively combined the University of North Carolina, the Woman’s College (now the University of North Carolina-Greensboro), and North Carolina State University. This conglomeration became the University of North Carolina in 1931. In 1937 Blake R Van Leer joined as Dean and started the graduate program for engineering. Following World War II, the university grew and developed. The G.I. Bill enabled thousands of veterans to attend college, and enrollment shot past the 5,000 mark in 1947.

State College created new academic programs, including the School of Architecture and Landscape Design in 1947 (renamed as the School of Design in 1948), the School of Education in 1948, and the School of Forestry in 1950. In the summer of 1956, following the US Supreme Court ruling in Brown v. Board of Education (1954) that segregated public education was unconstitutional, North Carolina State College enrolled its first African-American undergraduates, Ed Carson, Manuel Crockett, Irwin Holmes, and Walter Holmes.

In 1962, State College officials desired to change the institution’s name to North Carolina State University. Consolidated university administrators approved a change to the University of North Carolina at Raleigh, frustrating many students and alumni who protested the change with letter writing campaigns. In 1963, State College officially became North Carolina State of the University of North Carolina. Students, faculty, and alumni continued to express dissatisfaction with this name, however, and after two additional years of protest, the name was changed to the current North Carolina State University at Raleigh. However, by longstanding convention, the “at Raleigh” portion is omitted, and the shorter names “North Carolina State University” and “NC State University” are accepted on first reference in news stories. Indeed, school officials discourage using “at Raleigh” except when absolutely necessary, as the full name implies that there is another branch of the university elsewhere in the state.

In 1966, single-year enrollment reached 10,000. In the 1970s enrollment surpassed 19,000 and the School of Humanities and Social Sciences was added.

Celebrating its centennial in 1987, North Carolina State University reorganized its internal structure, renaming all its schools to colleges (e.g. School of Engineering to the College of Engineering). Also in this year, it gained 700 acres (2.8 km^2) of land that was developed as Centennial Campus. Since then, North Carolina State University has focused on developing its new Centennial Campus. It has invested more than $620 million in facilities and infrastructure at the new campus, with 62 acres (0.3 km^2) of space being constructed. Sixty-one private and government agency partners are located on Centennial Campus.

North Carolina State University has almost 8,000 employees, nearly 35,000 students, a $1.495 billion annual budget, and a $1.4 billion endowment. It is the largest university in the state and one of the anchors of North Carolina’s Research Triangle, together with Duke University and the University of North Carolina- Chapel Hill.

In 2009, North Carolina State University canceled a planned appearance by the Dalai Lama to speak on its Raleigh campus, citing concerns about a Chinese backlash and a shortage of time and resources.

North Carolina State University Libraries Special Collections Research Center, located in D.H. Hill Library, maintains a website devoted to NC State history entitled Historical State.

North Carolina State University is one of 17 institutions that constitute the University of North Carolina system. Each campus has a high degree of independence, but each submits to the policies of the UNC system Board of Governors. The 32 voting members of the Board of Governors are elected by the North Carolina General Assembly for four-year terms. President Thomas W. Ross heads the system.

The Board of Trustees of North Carolina State University has thirteen members and sets all policies for the university. The UNC system Board of Governors elects eight of the trustees and the Governor of North Carolina appoints four. The student body president serves on the Board of Trustees as a voting member. The UNC system also elects the Chancellor of North Carolina State University.

The Board of Trustees administers North Carolina State University’s eleven academic colleges. Each college grants its own degrees with the exception of the First Year College which provides incoming freshmen the opportunity to experience several disciplines before selecting a major. The College of Agriculture and Life Sciences is the only college to offer associate’s degrees and the College of Veterinary Medicine does not grant undergraduate degrees. Each college is composed of numerous departments that focus on a particular discipline or degree program, for example Food Science, Civil Engineering, Genetics or Accounting. There are a total of 66 departments administered by all eleven NC State colleges.

In total, North Carolina State University offers nine associate’s degrees in agriculture, bachelor’s degrees in 102 areas of study, master’s degrees in 108 areas and doctorate degrees in 60 areas. North Carolina State University is known for its programs in agriculture, engineering, textiles, and design. The textile and paper engineering programs are notable, given the uniqueness of the subject area.

As of the 2018-2019 school year, North Carolina State University has the following colleges and academic departments:

College of Agriculture and Life Sciences
College of Design
College of Education
College of Engineering
College of Humanities and Social Sciences
College of Natural Resources
Poole College of Management
College of Sciences
Wilson College of Textiles
College of Veterinary Medicine
The Graduate School
University College

In 2014 – 2015 North Carolina State University became part of only fifty-four institutions in the U.S. to have earned the “Innovation and Economic Prosperity University” designation by the Association of Public and Land-grant Universities.

For 2020, U.S. News & World Report ranks North Carolina State University tied for 84th out of all national universities and tied for 34th out of public universities in the U.S., tied at 31st for “most innovative” and 69th for “best value” schools.

North Carolina State University’s College of Engineering was tied for 24th by U.S. News & World Report, with many of its programs ranking in the top 30 nationally. North Carolina State University’s Nuclear Engineering program is considered to be one of the best in the world and in 2020, was ranked 3rd in the country (behind The Massachusetts Institute of Technology and the University of Michigan-Ann Arbor ). The biological and agricultural engineering programs are also widely recognized and were ranked 4th nationally. In 2019 North Carolina State University’s manufacturing and industrial engineering program was ranking 13th in the nation, and material science at 15th. Other notable programs included civil engineering at 20th, environmental engineering tied at 21st, chemical engineering tied for 22nd, computer engineering at 28th, and biomedical engineering ranking 28th nationally in 2019. In 2019, the Academic Ranking of World Universities ranked NC State’s electrical engineering program 9th internationally and chemical engineering 20th. In 2020, The Princeton Review ranked NC State 36th for game design.

North Carolina State University is also home to the only college dedicated to textiles in the country, the Wilson College of Textiles, which is a partner of the National Council of Textile Organizations and is widely regarded as one of the best textiles programs in the world. In 2020 the textile engineering program was ranked 1st nationally by College Factual. In 2017, Business of Fashion Magazine ranked the college’s fashion and apparel design program 8th in the country and 30th in the world. In 2018, Fashion Schools ranked the college’s fashion and textile management program 11th in the nation.

North Carolina State University’s Masters program in Data Analytics was the first in the United States. Launched in 2007, it is part of the Institute for Advanced Analytics and was created as a university-wide multidisciplinary initiative to meet the rapidly growing demand in the labor market for analytics professionals. In 2012, Thomas H. Davenport and D.J. Patil highlighted the MSA program in Harvard Business Review as one of only a few sources of talent with proven strengths in data science.

North Carolina State University is known for its College of Veterinary Medicine and in 2020 it was ranked 4th nationally, by U.S. News & World Report, 25th internationally by NTU Ranking and 36th internationally by the Academic Ranking of World Universities.

In 2020, North Carolina State University’s College of Design was ranked 25th by College Factual. In 2018, the Animation Career Review ranked North Carolina State University’s Graphic Design program 4th in the country and best among public universities.

In 2020, the College of Education tied for 45th in the U.S. and the Poole College of Management is tied for 52nd among business schools. North Carolina State University’s Entrepreneurship program is ranked 10th internationally among undergraduate programs by The Princeton Review in 2020. For 2010 the Wall Street Journal surveyed recruiters and ranked NC State number 19 among the top 25 recruiter picks. In 2018, U.S. News & World Report ranked the Department of Statistics 16th (tied) in the nation.

In fiscal year 2019, North Carolina State University received 95 awards and $29,381,782 in National Institutes of Health (NIH) Funds for Research. For fiscal year 2017, NC State was ranked 45th in total research expenditure by the National Science Foundation.

Kiplinger’s Personal Finance placed North Carolina State University 9th in its 2018 ranking of best value public colleges in the United States.

From The DOE’s Lawrence Berkeley National Laboratory: “How to Edit the Genes of Nature’s Master Manipulators”

From The DOE’s Lawrence Berkeley National Laboratory

12.5.22
Aliyah Kovner

Scientists are using CRISPR to engineer the viruses that evolved to engineer bacteria.

(Credit: Davian Ho)

CRISPR, the Nobel Prize-winning gene editing technology, is poised to have a profound impact on the fields of microbiology and medicine yet again.

A team led by CRISPR pioneer Jennifer Doudna and her longtime collaborator Jill Banfield has developed a clever tool to edit the genomes of bacteria-infecting viruses called bacteriophages using a rare form of CRISPR. The ability to easily engineer custom-designed phages – which has long eluded the research community – could help researchers control microbiomes without antibiotics or harsh chemicals, and treat dangerous drug-resistant infections. A paper describing the work was recently published in Nature Microbiology [below].

Fig. 1: Maximum-likelihood phylogeny of Cas13 proteins and their distribution across the bacterial tree of life.

The four known subtypes, Cas13a–d, each form their clade (inner track) with a skewed distribution across bacterial taxa (outer track). A Vibrio cholerae Cas9 (UIO88932.1) was used as the outgroup. Cas13 subtypes and microbial taxa that encode Cas13 are denoted in the colour bar.

Fig. 2: Comparison of Cas13a and Cas13d in E. coli phage challenge assays with lytic phage T4.

a, Experimental architecture of Cas13 phage defence. Cas13 is expressed under aTc control alongside a crRNA. During phage infection, Cas13 unleashes toxic cis- and trans-cleavage if Cas13 detects its crRNA target. b, crRNA architecture employed in this study. c, Overview of T4 genes and transcript locations targeted by Cas13 in T4 phage challenge experiments. Approximate gene architecture is shown in forward orientation. crRNA locations are highlighted in orange. d, T4 phage infection in bacteria expressing phage-targeting crRNA and either LbuCas13a or RfxCas13d. EOP values represent the average of three biological replicates for a single crRNA. EOP data are presented as mean ± s.d. e, T4 phage plaque assays comparing the efficacy of Cas13a and toxicity of Cas13d. A representative plaque assay from three biological replicates is shown. An RFP-targeting crRNA is shown as a negative control.

“Bacteriophages are some of the most abundant and diverse biological entities on Earth. Unlike prior approaches, this editing strategy works against the tremendous genetic diversity of bacteriophages,” said first author Benjamin Adler, a postdoctoral fellow in Doudna’s lab. “There are so many exciting directions here – discovery is literally at our fingertips!”

An atomic structural model of a T4 phage, the type edited in this research. (Credit: Dr. Victor Padilla-Sanchez/Wikimedia Commons)

Bacteriophages, also simply called phages, insert their genetic material into bacterial cells using a syringe-like apparatus, then hijack the protein-building machinery of their hosts in order to reproduce themselves – usually killing the bacteria in the process. (They’re harmless to other organisms, including us humans, even though electron microscopy images have revealed that they look like sinister alien spaceships.)

CRISPR-Cas is a type of immune defense mechanism that many bacteria and archaea use against phages. A CRISPR-Cas system consists of short snippets of RNA that are complementary to sequences in phage genes, allowing the microbe to recognize when invasive genetic material has been inserted, and scissor-like enzymes that neutralize the phage genes by cutting them into harmless pieces, after being guided into place by the RNA.

Over millennia, the perpetual evolutionary battle between phage offense and bacterial defense forced phages to specialize. There are a lot of microbes, so there are also a lot of phages, each with unique adaptations. This astounding diversity has made phage editing difficult, including making them resistant to many forms of CRISPR, which is why the most commonly used system – CRISPR-Cas9 – doesn’t work for this application.

“Phages have many ways to evade defenses, ranging from anti-CRISPRs to just being good at repairing their own DNA,” said Adler. “So, in a sense, the adaptations encoded in phage genomes that make them so good at manipulating microbes are the exact same reason why it has been so difficult to develop a general-purpose tool for editing their genomes.”

Project leaders Doudna and Banfield have developed numerous CRISPR-based tools together since they first collaborated on an early investigation of CRISPR in 2008. That work – performed at Lawrence Berkeley National Laboratory – was cited by the Nobel Prize committee when Doudna and her other collaborator, Emmanuelle Charpentier, received the prize in 2020. Doudna and Banfield’s team of Berkeley Lab and University of California-Berkeley researchers were studying the properties of a rare form of CRISPR called CRISPR-Cas13 (derived from a bacterium commonly found in the human mouth) when they discovered that this version of the defense system works against a huge range of phages.

The phage-fighting potency of CRISPR-Cas13 was unexpected given how few microbes use it, explained Adler. The scientists were doubly surprised because the phages it defeated in testing all infect using double-stranded DNA, but the CRISPR-Cas13 system only targets and chops single-stranded viral RNA. Like other types of viruses, some phages have DNA-based genomes and some have RNA-based genomes. However, all known viruses use RNA to express their genes. The CRISPR-Cas13 system effectively neutralized nine different DNA phages that all infect strains of E. coli, yet have almost no similarity across their genomes.

According to co-author and phage expert Vivek Mutalik, a staff scientist in Berkeley Lab’s Biosciences Area, these findings indicate that the CRISPR system can defend against diverse DNA-based phages by targeting their RNA after it has been converted from DNA by the bacteria’s own enzymes prior to protein translation.

Next, the team demonstrated that the system can be used to edit phage genomes rather than just chop them up defensively.

First, they made segments of DNA composed of the phage sequence they wanted to create flanked by native phage sequences, and put them into the phage’s target bacteria. When the phages infected the DNA-laden microbes, a small percentage of the phages reproducing inside the microbes took up the altered DNA and incorporated it into their genomes in place of the original sequence. This step is a longstanding DNA editing technique called homologous recombination. The decades-old problem in phage research is that although this step, the actual phage genome editing, works just fine, isolating and replicating the phages with the edited sequence from the larger pool of normal phages is very tricky.

This is where the CRISPR-Cas13 comes in. In step two, the scientists engineered another strain of host microbe to contain a CRISPR-Cas13 system that senses and defends against the normal phage genome sequence. When the phages made in step one were exposed to the second-round hosts, the phages with the original sequence were defeated by the CRISPR defense system, but the small number of edited phages were able to evade it. They survived and replicated themselves.

Experiments with three unrelated E. coli phages showed a staggering success rate: more than 99% of the phages produced in the two-step processes contained the edits, which ranged from enormous multi-gene deletions all the way down to precise replacements of a single amino acid.

“In my opinion, this work on phage engineering is one of the top milestones in phage biology,” said Mutalik. “As phages impact microbial ecology, evolution, population dynamics, and virulence, seamless engineering of bacteria and their phages has profound implications for foundational science, but also has the potential to make a real difference in all aspects of the bioeconomy. In addition to human health, this phage engineering capability will impact everything from biomanufacturing and agriculture to food production.”

Buoyed by their initial results, the scientists are currently working to expand the CRISPR system to use it on more types of phages, starting with ones that impact microbial soil communities. They are also using it as a tool to explore the genetic mysteries within phage genomes. Who knows what other amazing tools and technologies can be inspired by the spoils of microscopic war between bacteria and virus?

This research was funded by the Department of Energy Microbial Community Analysis & Functional Evaluation in Soils (m-CAFES) Scientific Focus Area. Jill Banfield is a professor of Earth and Planetary Science and Environmental Science, Policy, & Management at The University of California-Berkeley as well as a faculty scientist in Berkeley Lab’s Biosciences Area and an affiliate in the Earth and Environmental Sciences Area. Jennifer Doudna is a professor in the Molecular and Cell Biology and Chemistry departments at The University of California-Berkeley and a faculty scientist in Berkeley Lab’s Biosciences Area.

Science paper:
Nature Microbiology
See the science paper for instructive material with more images.

See the full article here .

Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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

Please help promote STEM in your local schools.

Stem Education Coalition

LBNL campus

Berkeley Lab campus Aerial View

Bringing Science Solutions to the World

In the world of science, The Lawrence Berkeley National Laboratory (Berkeley Lab) is synonymous with “excellence.” Thirteen Nobel prizes are associated with Berkeley Lab. Seventy Lab scientists are members of the The National Academy of Sciences, one of the highest honors for a scientist in the United States. Thirteen of our scientists have won the National Medal of Science, our nation’s highest award for lifetime achievement in fields of scientific research. Eighteen of our engineers have been elected to the The National Academy of Engineering, and three of our scientists have been elected into The Institute of Medicine. In addition, Berkeley Lab has trained thousands of university science and engineering students who are advancing technological innovations across the nation and around the world.

Berkeley Lab is a member of the national laboratory system supported by The DOE through its Office of Science. It is managed by the University of California and is charged with conducting unclassified research across a wide range of scientific disciplines. Located on a 202-acre site in the hills above The University of California-Berkeley campus that offers spectacular views of the San Francisco Bay, Berkeley Lab employs approximately 3,232 scientists, engineers and support staff. The Lab’s total costs for FY 2014 were $785 million. A recent study estimates the Laboratory’s overall economic impact through direct, indirect and induced spending on the nine counties that make up the San Francisco Bay Area to be nearly $700 million annually. The Lab was also responsible for creating 5,600 jobs locally and 12,000 nationally. The overall economic impact on the national economy is estimated at $1.6 billion a year. Technologies developed at Berkeley Lab have generated billions of dollars in revenues, and thousands of jobs. Savings as a result of Berkeley Lab developments in lighting and windows, and other energy-efficient technologies, have also been in the billions of dollars.

Berkeley Lab was founded in 1931 by Ernest Orlando Lawrence, a University of California-Berkeley physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab legacy that continues today.

History

1931–1941

The laboratory was founded on August 26, 1931, by Ernest Lawrence, as the Radiation Laboratory of the University of California-Berkeley, associated with the Physics Department. It centered physics research around his new instrument, the cyclotron, a type of particle accelerator for which he was awarded the Nobel Prize in Physics in 1939.

E.O. Lawrence’ first cyclotron.

LBNL 88 inch cyclotron.

LBNL 88 inch cyclotron.

Throughout the 1930s, Lawrence pushed to create larger and larger machines for physics research, courting private philanthropists for funding. He was the first to develop a large team to build big projects to make discoveries in basic research. Eventually these machines grew too large to be held on the university grounds, and in 1940 the lab moved to its current site atop the hill above campus. Part of the team put together during this period includes two other young scientists who went on to establish large laboratories; J. Robert Oppenheimer founded The DOE’s Los Alamos Laboratory, and Robert Wilson founded The DOE’s Fermi National Accelerator Laboratory.

1942–1950

Leslie Groves visited Lawrence’s Radiation Laboratory in late 1942 as he was organizing the Manhattan Project, meeting J. Robert Oppenheimer for the first time. Oppenheimer was tasked with organizing the nuclear bomb development effort and founded today’s Los Alamos National Laboratory to help keep the work secret. At the RadLab, Lawrence and his colleagues developed the technique of electromagnetic enrichment of uranium using their experience with cyclotrons. The “calutrons” (named after the University) became the basic unit of the massive Y-12 facility in Oak Ridge, Tennessee. Lawrence’s lab helped contribute to what have been judged to be the three most valuable technology developments of the war (the atomic bomb, proximity fuse, and radar). The cyclotron, whose construction was stalled during the war, was finished in November 1946. The Manhattan Project shut down two months later.

1951–2018

After the war, the Radiation Laboratory became one of the first laboratories to be incorporated into the Atomic Energy Commission (AEC) (now The Department of Energy . The most highly classified work remained at Los Alamos, but the RadLab remained involved. Edward Teller suggested setting up a second lab similar to Los Alamos to compete with their designs. This led to the creation of an offshoot of the RadLab (now The DOE’s Lawrence Livermore National Laboratory) in 1952. Some of the RadLab’s work was transferred to the new lab, but some classified research continued at Berkeley Lab until the 1970s, when it became a laboratory dedicated only to unclassified scientific research.

Shortly after the death of Lawrence in August 1958, the UC Radiation Laboratory (both branches) was renamed the Lawrence Radiation Laboratory. The Berkeley location became the Lawrence Berkeley Laboratory in 1971, although many continued to call it the RadLab. Gradually, another shortened form came into common usage, LBNL. Its formal name was amended to Ernest Orlando Lawrence Berkeley National Laboratory in 1995, when “National” was added to the names of all DOE labs. “Ernest Orlando” was later dropped to shorten the name. Today, the lab is commonly referred to as “Berkeley Lab”.

The Alvarez Physics Memos are a set of informal working papers of the large group of physicists, engineers, computer programmers, and technicians led by Luis W. Alvarez from the early 1950s until his death in 1988. Over 1700 memos are available on-line, hosted by the Laboratory.

The lab remains owned by the Department of Energy , with management from the University of California. Companies such as Intel were funding the lab’s research into computing chips.

Science mission

From the 1950s through the present, Berkeley Lab has maintained its status as a major international center for physics research, and has also diversified its research program into almost every realm of scientific investigation. Its mission is to solve the most pressing and profound scientific problems facing humanity, conduct basic research for a secure energy future, understand living systems to improve the environment, health, and energy supply, understand matter and energy in the universe, build and safely operate leading scientific facilities for the nation, and train the next generation of scientists and engineers.

The Laboratory’s 20 scientific divisions are organized within six areas of research: Computing Sciences; Physical Sciences; Earth and Environmental Sciences; Biosciences; Energy Sciences; and Energy Technologies. Berkeley Lab has six main science thrusts: advancing integrated fundamental energy science; integrative biological and environmental system science; advanced computing for science impact; discovering the fundamental properties of matter and energy; accelerators for the future; and developing energy technology innovations for a sustainable future. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab tradition that continues today.

Berkeley Lab operates five major National User Facilities for the DOE Office of Science:

The Advanced Light Source (ALS) is a synchrotron light source with 41 beam lines providing ultraviolet, soft x-ray, and hard x-ray light to scientific experiments.

The DOE’s Lawrence Berkeley National Laboratory Advanced Light Source.
The ALS is one of the world’s brightest sources of soft x-rays, which are used to characterize the electronic structure of matter and to reveal microscopic structures with elemental and chemical specificity. About 2,500 scientist-users carry out research at ALS every year. Berkeley Lab is proposing an upgrade of ALS which would increase the coherent flux of soft x-rays by two-three orders of magnitude.

Berkeley Lab Laser Accelerator (BELLA) Center

A view of BELLA, the Berkeley Lab Laser Accelerator. Credit: Roy Kaltschmidt-Berkeley Lab.

The DOE Joint Genome Institute supports genomic research in support of the DOE missions in alternative energy, global carbon cycling, and environmental management. The JGI’s partner laboratories are Berkeley Lab, DOE’s Lawrence Livermore National Laboratory, DOE’s Oak Ridge National Laboratory (ORNL), DOE’s Pacific Northwest National Laboratory (PNNL), and the HudsonAlpha Institute for Biotechnology . The JGI’s central role is the development of a diversity of large-scale experimental and computational capabilities to link sequence to biological insights relevant to energy and environmental research. Approximately 1,200 scientist-users take advantage of JGI’s capabilities for their research every year.

LBNL Molecular Foundry

The LBNL Molecular Foundry is a multidisciplinary nanoscience research facility. Its seven research facilities focus on Imaging and Manipulation of Nanostructures; Nanofabrication; Theory of Nanostructured Materials; Inorganic Nanostructures; Biological Nanostructures; Organic and Macromolecular Synthesis; and Electron Microscopy. Approximately 700 scientist-users make use of these facilities in their research every year.

The DOE’s NERSC National Energy Research Scientific Computing Center is the scientific computing facility that provides large-scale computing for the DOE’s unclassified research programs. Its current systems provide over 3 billion computational hours annually. NERSC supports 6,000 scientific users from universities, national laboratories, and industry.

DOE’s NERSC National Energy Research Scientific Computing Center at Lawrence Berkeley National Laboratory.

Cray Cori II supercomputer at National Energy Research Scientific Computing Center at DOE’s Lawrence Berkeley National Laboratory, named after Gerty Cori, the first American woman to win a Nobel Prize in science.

NERSC Hopper Cray XE6 supercomputer.

NERSC Cray XC30 Edison supercomputer.

NERSC GPFS for Life Sciences.

The Genepool system is a cluster dedicated to the DOE Joint Genome Institute’s computing needs. Denovo is a smaller test system for Genepool that is primarily used by NERSC staff to test new system configurations and software.

NERSC PDSF computer cluster in 2003.

PDSF is a networked distributed computing cluster designed primarily to meet the detector simulation and data analysis requirements of physics, astrophysics and nuclear science collaborations.

Cray Shasta Perlmutter SC18 AMD Epyc Nvidia pre-exascale supercomputer.

NERSC is a DOE Office of Science User Facility.

The DOE’s Energy Science Network is a high-speed network infrastructure optimized for very large scientific data flows. ESNet provides connectivity for all major DOE sites and facilities, and the network transports roughly 35 petabytes of traffic each month.

Berkeley Lab is the lead partner in the DOE’s Joint Bioenergy Institute (JBEI), located in Emeryville, California. Other partners are the DOE’s Sandia National Laboratory, the University of California (UC) campuses of Berkeley and Davis, the Carnegie Institution for Science , and DOE’s Lawrence Livermore National Laboratory (LLNL). JBEI’s primary scientific mission is to advance the development of the next generation of biofuels – liquid fuels derived from the solar energy stored in plant biomass. JBEI is one of three new U.S. Department of Energy (DOE) Bioenergy Research Centers (BRCs).

Berkeley Lab has a major role in two DOE Energy Innovation Hubs. The mission of the Joint Center for Artificial Photosynthesis (JCAP) is to find a cost-effective method to produce fuels using only sunlight, water, and carbon dioxide. The lead institution for JCAP is the California Institute of Technology and Berkeley Lab is the second institutional center. The mission of the Joint Center for Energy Storage Research (JCESR) is to create next-generation battery technologies that will transform transportation and the electricity grid. DOE’s Argonne National Laboratory leads JCESR and Berkeley Lab is a major partner.

From The Massachusetts Institute of Technology: “New CRISPR-based tool inserts large DNA sequences at desired sites in cells”

From The Massachusetts Institute of Technology

11.24.22
Anne Trafton

Building on the CRISPR gene-editing system, MIT researchers designed a new tool that can snip out faulty genes and replace them with new ones. Image: MIT News, with images from iStockphoto.

Building on the CRISPR gene-editing system, MIT researchers have designed a new tool that can snip out faulty genes and replace them with new ones, in a safer and more efficient way.

Using this system, the researchers showed that they could deliver genes as long as 36,000 DNA base pairs to several types of human cells, as well as to liver cells in mice. The new technique, known as PASTE, could hold promise for treating diseases that are caused by defective genes with a large number of mutations, such as cystic fibrosis.

“It’s a new genetic way of potentially targeting these really hard to treat diseases,” says Omar Abudayyeh, a McGovern Fellow at MIT’s McGovern Institute for Brain Research. “We wanted to work toward what gene therapy was supposed to do at its original inception, which is to replace genes, not just correct individual mutations.”

The new tool combines the precise targeting of CRISPR-Cas9, a set of molecules originally derived from bacterial defense systems, with enzymes called integrases, which viruses use to insert their own genetic material into a bacterial genome.

“Just like CRISPR, these integrases come from the ongoing battle between bacteria and the viruses that infect them,” says Jonathan Gootenberg, also a McGovern Fellow. “It speaks to how we can keep finding an abundance of interesting and useful new tools from these natural systems.”

Gootenberg and Abudayyeh are the senior authors of the new study, which appears today in Nature Biotechnology [below]. The lead authors of the study are MIT technical associates Matthew Yarnall and Rohan Krajeski, former MIT graduate student Eleonora Ioannidi, and MIT graduate student Cian Schmitt-Ulms.

DNA insertion

The CRISPR-Cas9 gene editing system consists of a DNA-cutting enzyme called Cas9 and a short RNA strand that guides the enzyme to a specific area of the genome, directing Cas9 where to make its cut. When Cas9 and the guide RNA targeting a disease gene are delivered into cells, a specific cut is made in the genome, and the cells’ DNA repair processes glue the cut back together, often deleting a small portion of the genome.

If a DNA template is also delivered, the cells can incorporate a corrected copy into their genomes during the repair process. However, this process requires cells to make double-stranded breaks in their DNA, which can cause chromosomal deletions or rearrangements that are harmful to cells. Another limitation is that it only works in cells that are dividing, as nondividing cells don’t have active DNA repair processes.

The MIT team wanted to develop a tool that could cut out a defective gene and replace it with a new one without inducing any double-stranded DNA breaks. To achieve this goal, they turned to a family of enzymes called integrases, which viruses called bacteriophages use to insert themselves into bacterial genomes.

For this study, the researchers focused on “serine integrases”, which can insert huge chunks of DNA, as large as 50,000 base pairs. These enzymes target specific genome sequences known as attachment sites, which function as “landing pads.” When they find the correct landing pad in the host genome, they bind to it and integrate their DNA payload.

In past work, scientists have found it challenging to develop these enzymes for human therapy because the landing pads are very specific, and it’s difficult to reprogram integrases to target other sites. The MIT team realized that combining these enzymes with a CRISPR-Cas9 system that inserts the correct landing site would enable easy reprogramming of the powerful insertion system.

The new tool, PASTE (Programmable Addition via Site-specific Targeting Elements), includes a Cas9 enzyme that cuts at a specific genomic site, guided by a strand of RNA that binds to that site. This allows them to target any site in the genome for insertion of the landing site, which contains 46 DNA base pairs. This insertion can be done without introducing any double-stranded breaks by adding one DNA strand first via a fused reverse transcriptase, then its complementary strand.

Once the landing site is incorporated, the integrase can come along and insert its much larger DNA payload into the genome at that site. 

“We think that this is a large step toward achieving the dream of programmable insertion of DNA,” Gootenberg says. “It’s a technique that can be easily tailored both to the site that we want to integrate as well as the cargo.”

Gene replacement

In this study, the researchers showed that they could use PASTE to insert genes into several types of human cells, including liver cells, T cells, and lymphoblasts (immature white blood cells). They tested the delivery system with 13 different payload genes, including some that could be therapeutically useful, and were able to insert them into nine different locations in the genome.

In these cells, the researchers were able to insert genes with a success rate ranging from 5 to 60 percent. This approach also yielded very few unwanted “indels” (insertions or deletions) at the sites of gene integration.

“We see very few indels, and because we’re not making double-stranded breaks, you don’t have to worry about chromosomal rearrangements or large-scale chromosome arm deletions,” Abudayyeh says.

The researchers also demonstrated that they could insert genes in “humanized” livers in mice. Livers in these mice consist of about 70 percent human hepatocytes, and PASTE successfully integrated new genes into about 2.5 percent of these cells.

The DNA sequences that the researchers inserted in this study were up to 36,000 base pairs long, but they believe even longer sequences could also be used. A human gene can range from a few hundred to more than 2 million base pairs, although for therapeutic purposes only the coding sequence of the protein needs to be used, drastically reducing the size of the DNA segment that needs to be inserted into the genome.

“The ability to site-specifically make large genomic integrations is of huge value to both basic science and biotechnology studies. This toolset will, I anticipate, be very enabling for the research community,” says Prashant Mali, a professor of bioengineering at the University of California at San Diego, who was not involved in the study.

The researchers are now further exploring the possibility of using this tool as a possible way to replace the defective cystic fibrosis gene. This technique could also be useful for treating blood diseases caused by faulty genes, such as hemophilia and G6PD deficiency, or Huntington’s disease, a neurological disorder caused by a defective gene that has too many gene repeats.

The researchers have also made their genetic constructs available online for other scientists to use.

“One of the fantastic things about engineering these molecular technologies is that people can build on them, develop and apply them in ways that maybe we didn’t think of or hadn’t considered,” Gootenberg says. “It’s really great to be part of that emerging community.”

The research was funded by a Swiss National Science Foundation Postdoc Mobility Fellowship, the U.S. National Institutes of Health, the McGovern Institute Neurotechnology Program, the K. Lisa Yang and Hock E. Tan Center for Molecular Therapeutics in Neuroscience, the G. Harold and Leila Y. Mathers Charitable Foundation, the MIT John W. Jarve Seed Fund for Science Innovation, Impetus Grants, a Cystic Fibrosis Foundation Pioneer Grant, Google Ventures, Fast Grants, the Harvey Family Foundation, and the McGovern Institute.

Science paper:
Nature Biotechnology

See the full article here .

Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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.

MIT Lincoln Laboratory campus

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.

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 “Physics” : “Predicting the Structures of Proteins” Kathryn Tunyasuvunakool

About Physics

From “Physics”

11.28.22
Katherine Wright

K. Tunyasuvunakool.

Kathryn Tunyasuvunakool grew up surrounded by scientific activities carried out at home by her mother—who went to university a few years after Tunyasuvunakool was born. One day a pendulum hung from a ceiling in her family’s home, Tunyasuvunakool’s mother standing next to it, timing the swings for a science assignment. Another day, fossil samples littered the dining table, her mother scrutinizing their patterns for a report. This early exposure to science imbued Tunyasuvunakool with the idea that science was fun and that having a career in science was an attainable goal. “From early on I was desperate to go to university and be a scientist,” she says.

Tunyasuvunakool fulfilled that ambition, studying math as an undergraduate, and computational biology as a graduate student. During her PhD work she helped create a model that captured various elements of the development of a soil-inhabiting roundworm called Caenorhabditis elegans, a popular organism for both biologists and physicists to study. She also developed a love for programming, which, she says, lent itself naturally to a jump into software engineering. Today Tunyasuvunakool is part of the team behind DeepMind’s AlphaFold—a protein-structure-prediction tool. Physics Magazine spoke to her to find out more about this software, which recently won two of its makers a Breakthrough Prize, and about why she’s excited for the potential discoveries it could enable.

What is AlphaFold and what can it be used for?

DeepMind puts the entire human proteome online, as folded by AlphaFold. Image Credit: DeepMind.

AlphaFold is a machine-learning model that can predict a protein’s structure from its amino-acid sequence. Protein sequences are relativity easy to obtain, with many experiments now able to quickly determine a given protein’s 1D amino-acid chain. But this sequence doesn’t explain how the protein will fold up into a 3D structure, which determines how the protein functions. Folded structures can be experimentally obtained but doing so is time consuming. AlphaFold can predict the structures in a fraction of the time, accelerating the understanding of these systems.

What is your role on the AlphaFold team?

When I first joined the team, I worked as a software engineer, writing data pipelines that take existing experimental protein-structure data and turn them into features we can use to train the model. While doing that, I became really interested in how useful AlphaFold’s predictions were. I started to scrutinize the predictions, performing detailed comparisons with literature findings. I then moved into doing that full time, evaluating model performance and finding applications for the software.

So, how good are AlphaFold’s predictions?

In 2020 I compared AlphaFold’s predictions to the structures found in experimental studies reported in the highest-impact journals, mostly those published in Nature. At the time we were trying to predict single-chain protein structures, and AlphaFold did really rather well. But I noticed that many of the papers weren’t looking at single chains, they were studying more complex systems that contained multiple chains.

That motivated us to start working on AlphaFold Multimer, a version of the model specifically trained for multichain protein complexes.

Have AlphaFold’s predictions ever disagreed with experimentally derived structures, which were then found to be wrong?

There have been a few cases; but they weren’t ones that I found. Since AlphaFold became available for anyone to use, researchers have carried out an enormous number of investigations with the software. One finding that came out of that effort is, in some instances, AlphaFold predicts more accurate structures than have been experimentally found with nuclear magnetic resonance (NMR) techniques. In NMR, the experimental data need quite a lot of processing to turn them into a structure. And there have been instances where AlphaFold’s predicted structure has fit the data better than the original NMR-derived one.

How many structures has AlphaFold predicted to date?

Over 200 million.

Any notable proteins whose structures you have worked on?

With the version of AlphaFold evaluated in CASP14 (the 14th iteration of a biennial assessment of protein-structure-prediction models), the first sequence I worked on was for one of the proteins of SARS-CoV-2, the virus that causes COVID-19. That was a sad way to start testing the system, but people were obviously interested in what that protein’s structure looked like.

What’s on the horizon for AlphaFold?

I can’t share many details, but I can say that the team behind AlphaFold is committed to working on protein-related problems for the long-term. There are still lots of things AlphaFold can’t do, such as modeling the nonprotein components bound to the system of interest or the influence of water molecules or ligands on how a given protein behaves. The 3D structure of a protein is also just one of its properties. It would be cool to be able to predict other things, such as how a protein’s shape is affected by point mutations.

There are about 20 people working on updates to AlphaFold—its success is really a team effort—and the team is constantly collaborating with researchers to make sure we are looking at problems that are of interest to scientists. We have a constant stream of follow-up problems to investigate.

See the full article here .

Comments are invited and will be appreciated, especially if the reader finds any errors which I can correct. Use “Reply”.

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

Please help promote STEM in your local schools.

Stem Education Coalition

Physicists are drowning in a flood of research papers in their own fields and coping with an even larger deluge in other areas of physics. How can an active researcher stay informed about the most important developments in physics? Physics highlights a selection of papers from the Physical Review journals. In consultation with expert scientists, the editors choose these papers for their importance and/or intrinsic interest. To highlight these papers, Physics features three kinds of articles: Viewpoints are commentaries written by active researchers, who are asked to explain the results to physicists in other subfields. Focus stories are written by professional science writers in a journalistic style and are intended to be accessible to students and non-experts. Synopses are brief editor-written summaries. Physics provides a much-needed guide to the best in physics, and we welcome your comments.

From Dartmouth College and The University of Vermont : “Dartmouth Study Offers New Insights into Genetic Mutations in Autism Disorders and Points to Possible Treatments”

From Dartmouth College

And

The University of Vermont

11.1.22
Timothy Dean

Findings from a new study published in Cell Reports [below], involving a collaborative effort between researchers at the Luikart Laboratory at Dartmouth’s Geisel School of Medicine and the Weston Laboratory at the University of Vermont, are providing further insight into the neurobiological basis of autism spectrum disorders (ASD) and pointing to possible treatments.

In recent years, researchers have established a strong association between certain mutated genes and ASD. One of the most common is called PTEN, which normally functions to control cell growth and regulate the ability of neurons to alter the strength of their connections. When mutated PTEN is a cause of not only ASD but also macrocephaly (enlarged head) and epilepsy.

(A) Schematic of experimental setup. Retroviruses encoding a fluorophore only (GFP) or a fluorophore and Cre recombinase (mCherry-T2A-Cre) were co-injected into dentate gyrus of Ptenflx/flx animals at postnatal day 7 (P7). Rapamycin (10 mg/kg of body weight) or vehicle was administered intraperitoneally from P10 to P31 daily. At P31, animals were perfused, and immunohistochemistry of hippocampal slices was performed for subsequent imaging and analysis.
(B) Top panel shows representative images of vehicle-treated immunolabeled granule neurons from Ptenflx/flx animals, while bottom panel shows representative images of rapamycin-treated immunolabeled granule neurons from Ptenflx/flx animals (scale bar represents 20 μm).
(C) Pten KO-mediated somal hypertrophy was completely rescued with rapamycin treatment, when compared with vehicle-treated Pten KO granule neurons.
(D) Rapamycin treatment of Pten KO granule neurons completely rescued the farther migration of vehicle-treated Pten KO granule neurons in the granule cell layer (GCL).
(E) Representative images for spine density analysis (scale bar represents 5 μm).
(F) The increased spine density of vehicle-treated Pten KO granule neurons was rescued by rapamycin treatment. The mixed-effects model in STATA was performed to determine p value (∗p < 0.05, ∗∗p < 0.01, ∗∗∗p < 0.001, ∗∗∗∗p < 0.0001). See Tables S1A–S1C for detailed statistics and quantitative results.

“In previous studies, our lab and many others have shown the PTEN mutations result in an increase in the number of excitatory synaptic connections between neurons in mice—which we believe could be the fundamental basis for the symptoms that are exhibited by ASD patients,” explains Bryan Luikart, PhD, an associate professor of molecular and systems biology at Dartmouth’s Geisel School of Medicine.

To mimic the genetic defects found in human autism patients, Luikart and his colleagues have engineered viruses to “knock out” the normal mouse PTEN gene and replace it with the mutated human PTEN gene. They then used sophisticated imaging and electrophysiological techniques to study how neuronal function was altered in mice.

“Essentially, what we’ve found is that it makes the neuron grow at twice the size of a normal neuron and in doing so forms about four times the number of synaptic connections with other neurons as a normal neuron,” says Luikart. He notes that the work served as a foundation for the new study, in which the research team sought to learn more about the role of other genes and signaling pathways in normal PTEN loss.

“We were able to determine that if you take out the gene known as Raptor, an essential gene in the mTORC1 signaling pathway, it rescues all of the neuronal overgrowth and synapses that occur with normal PTEN loss,” he says. “We also found that by using the drug Rapamycin to inhibit the mTORC1 pathway—which is necessary for neuronal growth and synapse formation—it rescues all of the changes in neuronal overgrowth.”

In a clinical trial earlier this year, when Rapamycin was administered to children it showed some benefit to the symptoms of autism. “One caveat is that our work is indicating that in order to have the best chance of having a therapeutic effect, these genetic changes associated with ASD really have to be targeted prior to the onset of symptoms.”

Still, the study’s findings have important implications for better understanding the neurological basis for ASD and developing effective therapies for patients.

“If we find that treating with a drug like Rapamycin early enough fixes the actual behavior problems of autism in a human patient, then that tells us we’re really on to something—that these changes that we’re seeing and fixing in our model organism are the cellular or physiological basis of autism in humans,” says Luikart.

Science paper:
Cell Reports
See the science paper for detailed material with images.

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 Vermont, officially The University of Vermont and State Agricultural College, is a public land-grant research university in Burlington, Vermont. It was founded in 1791 and is among the oldest universities in the United States as it was the fifth institution of higher education established in the New England region of the U.S. northeast. It is also listed as one of the original eight “Public Ivy” institutions in the United States. It is classified among “R2: Doctoral Universities – High research activity”.

The university’s Dudley H. Davis Center was the first student center in the United States to receive a Leadership in Energy and Environmental Design (LEED) Gold certification. The largest hospital complex in Vermont, the University of Vermont Medical Center, has its primary facility on the UVM campus and is affiliated with the Robert Larner College of Medicine.

The University of Vermont was founded as a private university in 1791, the same year Vermont became the 14th U.S. state. The university enrolled its first students 10 years later. Its first president, The Rev. Daniel C. Sanders, was hired in 1800, and served as the sole faculty member for seven years. Instruction began in 1801, and the first class graduated in 1804. In 1865, the university merged with Vermont Agricultural College (chartered November 22, 1864, after the passage of the Morrill Land-Grant Colleges Act), emerging as the University of Vermont and State Agricultural College. The university was granted 150,000 acres, which it sold for $122,626. The University of Vermont draws 6.8 percent of its annual budget of about $600 million from the State of Vermont and Vermont residents make up 35 percent of enrollment, while 65 percent of students come from elsewhere.

Much of the initial funding and planning for the university was undertaken by Ira Allen, who is honored as UVM’s founder. Allen donated a 50-acre (20 ha) parcel of land for establishment of the university. Most of this land has been maintained as the university’s main green, where stands a statue of Allen.

The citizens of Burlington helped fund the university’s first edifice, and, when it was destroyed by fire in 1824, also paid for its replacement. This building came to be known as “Old Mill” for its resemblance to New England mills of the time. The Marquis de Lafayette, a French general who became a commander in the American Revolution, toured all 24 U.S. states in 1824-1825 and while in Vermont laid the cornerstone of Old Mill, which stands on University Row, along with Ira Allen Chapel, Billings Library, Williams Hall, Royall Tyler Theatre and Morrill Hall. A statue of Lafayette stands at the north end of the main green.

The University of Vermont was the first American college or university with a charter declaring that the “rules, regulations, and by-laws shall not tend to give preference to any religious sect or denomination whatsoever.”

In 1871, UVM defied custom and admitted two women as students. Four years later, it was the first American university to admit women to full membership into the Phi Beta Kappa Society, the country’s oldest collegiate academic honor society. Likewise, in 1877, it initiated the first African American into the society.

Justin Smith Morrill, a U.S. Representative (1855-1867) and Senator (1867-1898) from Vermont, author of the Morrill Land-Grant Colleges Act that created federal funding for establishing the U.S. Land-Grant colleges and universities, served as a trustee of the university from 1865 to 1898.

In 1924, the first radio broadcast in Vermont occurred from the college station, WCAX, run by students then, now the call sign of a commercial television station.

For 73 years, until 1969, UVM held an annual “Kake Walk” where students wore blackface.

The University of Vermont comprises seven undergraduate schools, an honors college, a graduate college, and a college of medicine. The Honors College does not offer its own degrees; students in the Honors College concurrently enroll in one of the university’s seven undergraduate colleges or schools.

Bachelors, masters, and doctoral programs are offered through the College of Agriculture and Life Sciences, the College of Arts and Sciences, the College of Education and Social Services, the College of Engineering and Mathematical Sciences, the College of Medicine, the College of Nursing and Health Sciences, the Graduate College, the Grossman School of Business, and the Rubenstein School of Environment and Natural Resources. The University of Vermont is accredited by the New England Commission of Higher Education.

UVM is ranked tied for 118th in U.S. News & World Report’s 2021 national university rankings, and is ranked tied for 54th among public universities.

In 2019, Forbes America’s Top Colleges list ranks UVM 168th overall out of 650 private and public colleges and universities in America, and also ranks it 48th in the “Public Colleges” category and 91st among “Research Universities.”

The University of Vermont is ranked 40th on a list published by BusinessWeek.com of the top 50 U.S. colleges and universities whose bachelor’s degree graduates earn the highest salaries.

In 2014, an analysis of federal data found The University of Vermont to be among the top ten schools in the United States with the highest total rape reports. There were 27 total rape reports on their main campus.

Dartmouth College is a private Ivy League research university in Hanover, New Hampshire. Established in 1769 by Eleazar Wheelock, Dartmouth is one of the nine colonial colleges chartered before the American Revolution and among the most prestigious in the United States. Although founded to educate Native Americans in Christian theology and the English way of life, the university primarily trained Congregationalist ministers during its early history before it gradually secularized, emerging at the turn of the 20th century from relative obscurity into national prominence.

Following a liberal arts curriculum, Dartmouth provides undergraduate instruction in 40 academic departments and interdisciplinary programs, including 60 majors in the humanities, social sciences, natural sciences, and engineering, and enables students to design specialized concentrations or engage in dual degree programs. In addition to the undergraduate faculty of arts and sciences, Dartmouth has four professional and graduate schools: the Geisel School of Medicine, the Thayer School of Engineering, the Tuck School of Business, and the Guarini School of Graduate and Advanced Studies. The university also has affiliations with the Dartmouth–Hitchcock Medical Center. Dartmouth is home to the Rockefeller Center for Public Policy and the Social Sciences, the Hood Museum of Art, the John Sloan Dickey Center for International Understanding, and the Hopkins Center for the Arts. With a student enrollment of about 6,700, Dartmouth is the smallest university in the Ivy League. Undergraduate admissions are highly selective with an acceptance rate of 6.24% for the class of 2026, including a 4.7% rate for regular decision applicants.

Situated on a terrace above the Connecticut River, Dartmouth’s 269-acre (109 ha) main campus is in the rural Upper Valley region of New England. The university functions on a quarter system, operating year-round on four ten-week academic terms. Dartmouth is known for its strong undergraduate focus, Greek culture, and wide array of enduring campus traditions. Its 34 varsity sports teams compete intercollegiately in the Ivy League conference of the NCAA Division I.

Dartmouth is consistently cited as a leading university for undergraduate teaching by U.S. News & World Report. In 2021, the Carnegie Classification of Institutions of Higher Education listed Dartmouth as the only majority-undergraduate, arts-and-sciences focused, doctoral university in the country that has “some graduate coexistence” and “very high research activity”.

The university has many prominent alumni, including 170 members of the U.S. Senate and the U.S. House of Representatives, 24 U.S. governors, 23 billionaires, 8 U.S. Cabinet secretaries, 3 Nobel Prize laureates, 2 U.S. Supreme Court justices, and a U.S. vice president. Other notable alumni include 79 Rhodes Scholars, 26 Marshall Scholarship recipients, and 14 Pulitzer Prize winners. Dartmouth alumni also include many CEOs and founders of Fortune 500 corporations, high-ranking U.S. diplomats, academic scholars, literary and media figures, professional athletes, and Olympic medalists.

Comprising an undergraduate population of 4,307 and a total student enrollment of 6,350 (as of 2016), Dartmouth is the smallest university in the Ivy League. Its undergraduate program, which reported an acceptance rate around 10 percent for the class of 2020, is characterized by the Carnegie Foundation and U.S. News & World Report as “most selective”. Dartmouth offers a broad range of academic departments, an extensive research enterprise, numerous community outreach and public service programs, and the highest rate of study abroad participation in the Ivy League.

Dartmouth, a liberal arts institution, offers a four-year Bachelor of Arts and ABET-accredited Bachelor of Engineering degree to undergraduate students. The college has 39 academic departments offering 56 major programs, while students are free to design special majors or engage in dual majors. For the graduating class of 2017, the most popular majors were economics, government, computer science, engineering sciences, and history. The Government Department, whose prominent professors include Stephen Brooks, Richard Ned Lebow, and William Wohlforth, was ranked the top solely undergraduate political science program in the world by researchers at The London School of Economics (UK) in 2003. The Economics Department, whose prominent professors include David Blanchflower and Andrew Samwick, also holds the distinction as the top-ranked bachelor’s-only economics program in the world.

In order to graduate, a student must complete 35 total courses, eight to ten of which are typically part of a chosen major program. Other requirements for graduation include the completion of ten “distributive requirements” in a variety of academic fields, proficiency in a foreign language, and completion of a writing class and first-year seminar in writing. Many departments offer honors programs requiring students seeking that distinction to engage in “independent, sustained work”, culminating in the production of a thesis. In addition to the courses offered in Hanover, Dartmouth offers 57 different off-campus programs, including Foreign Study Programs, Language Study Abroad programs, and Exchange Programs.

Through the Graduate Studies program, Dartmouth grants doctorate and master’s degrees in 19 Arts & Sciences graduate programs. Although the first graduate degree, a PhD in classics, was awarded in 1885, many of the current PhD programs have only existed since the 1960s. Furthermore, Dartmouth is home to three professional schools: the Geisel School of Medicine (established 1797), Thayer School of Engineering (1867)—which also serves as the undergraduate department of engineering sciences—and Tuck School of Business (1900). With these professional schools and graduate programs, conventional American usage would accord Dartmouth the label of “Dartmouth University”; however, because of historical and nostalgic reasons (such as Dartmouth College v. Woodward), the school uses the name “Dartmouth College” to refer to the entire institution.

Dartmouth employs a total of 607 tenured or tenure-track faculty members, including the highest proportion of female tenured professors among the Ivy League universities, and the first black woman tenure-track faculty member in computer science at an Ivy League university. Faculty members have been at the forefront of such major academic developments as the Dartmouth Workshop, the Dartmouth Time Sharing System, Dartmouth BASIC, and Dartmouth ALGOL 30. In 2005, sponsored project awards to Dartmouth faculty research amounted to $169 million.

Dartmouth serves as the host institution of the University Press of New England, a university press founded in 1970 that is supported by a consortium of schools that also includes Brandeis University, The University of New Hampshire, Northeastern University, Tufts University and The University of Vermont.

Rankings

Dartmouth was ranked tied for 13th among undergraduate programs at national universities by U.S. News & World Report in its 2021 rankings. U.S. News also ranked the school 2nd best for veterans, tied for 5th best in undergraduate teaching, and 9th for “best value” at national universities in 2020. Dartmouth’s undergraduate teaching was previously ranked 1st by U.S. News for five years in a row (2009–2013). Dartmouth College is accredited by The New England Commission of Higher Education.

In Forbes’ 2019 rankings of 650 universities, liberal arts colleges and service academies, Dartmouth ranked 10th overall and 10th in research universities. In the Forbes 2018 “grateful graduate” rankings, Dartmouth came in first for the second year in a row.

The 2021 Academic Ranking of World Universities ranked Dartmouth among the 90–110th best universities in the nation. However, this specific ranking has drawn criticism from scholars for not adequately adjusting for the size of an institution, which leads to larger institutions ranking above smaller ones like Dartmouth. Dartmouth’s small size and its undergraduate focus also disadvantage its ranking in other international rankings because ranking formulas favor institutions with a large number of graduate students.

The 2006 Carnegie Foundation classification listed Dartmouth as the only “majority-undergraduate”, “arts-and-sciences focus[ed]”, “research university” in the country that also had “some graduate coexistence” and “very high research activity”.

The Dartmouth Plan

Dartmouth functions on a quarter system, operating year-round on four ten-week academic terms. The Dartmouth Plan (or simply “D-Plan”) is an academic scheduling system that permits the customization of each student’s academic year. All undergraduates are required to be in residence for the fall, winter, and spring terms of their freshman and senior years, as well as the summer term of their sophomore year. However, students may petition to alter this plan so that they may be off during their freshman, senior, or sophomore summer terms. During all terms, students are permitted to choose between studying on-campus, studying at an off-campus program, or taking a term off for vacation, outside internships, or research projects. The typical course load is three classes per term, and students will generally enroll in classes for 12 total terms over the course of their academic career.

The D-Plan was instituted in the early 1970s at the same time that Dartmouth began accepting female undergraduates. It was initially devised as a plan to increase the enrollment without enlarging campus accommodations, and has been described as “a way to put 4,000 students into 3,000 beds”. Although new dormitories have been built since, the number of students has also increased and the D-Plan remains in effect. It was modified in the 1980s in an attempt to reduce the problems of lack of social and academic continuity.

From The DOE’s Lawrence Berkeley National Laboratory: “Methane-Eating ‘Borgs’ Have Been Assimilating Earth’s Microbes”

From The DOE’s Lawrence Berkeley National Laboratory

10.19.22
Aliyah Kovner

A digital illustration inspired by methane-eating archaea and the Borgs that assimilate them (Credit: Jenny Nuss/Berkeley Lab)

A newly discovered type of transferrable DNA structure with a sci-fi name appears to play a role in balancing atmospheric methane.

In Star Trek, the Borg are a ruthless, hive-minded collective that assimilate other beings with the intent of taking over the galaxy. Here on nonfictional planet Earth, Borgs are DNA packages that could help humans fight climate change.

Last year, a team led by Jill Banfield discovered DNA structures within a methane-consuming microbe called Methanoperedens that appear to supercharge the organism’s metabolic rate. They named the genetic elements “Borgs” because the DNA within them contains genes assimilated from many organisms. In a study published today in Nature [below], the researchers describe the curious collection of genes within Borgs and begin to investigate the role these DNA packages play in environmental processes, such as carbon cycling.

First contact

Methanoperedens are a type of archaea (unicellular organisms that resemble bacteria but represent a distinct branch of life) that break down methane (CH4) in soils, groundwater, and the atmosphere to support cellular metabolism. Methanoperedens and other methane-consuming microbes live in diverse ecosystems around the world but are believed to be less common than microbes that use photosynthesis, oxygen, or fermentation for energy. Yet they play an outsized role in Earth system processes by removing methane – the most potent greenhouse gas – from the atmosphere. Methane traps 30 times more heat than carbon dioxide and is estimated to account for about 30 percent of human-driven global warming. The gas is emitted naturally through geological processes and by methane-generating archaea; however, industrial processes are releasing stored methane back into the atmosphere in worrying quantities.

Banfield, a faculty scientist at Lawrence Berkeley National Laboratory (Berkeley Lab) and professor of Earth & Planetary Science and Environmental Science, Policy & Management at UC Berkeley, studies how microbial activities shape large-scale environmental processes and how, in turn, environmental fluctuations alter the planet’s microbiomes. As part of this work, she and her colleagues regularly sample microbes in different habitats to see what interesting genes microbes are using for survival, and how these genes might affect global cycles of key elements, such as carbon, nitrogen, and sulfur. The team looks at the genomes within cells as well as the portable packets of DNA known as extra-chromosomal elements (ECEs) that transfer genes between bacteria, archaea, and viruses. These elements allow microbes to quickly gain beneficial genes from their neighbors, including those that are only distantly related.

Jill Banfield, left, and Kenneth Williams collect a sample of water from the East River in Colorado to study the ecosystem’s microbial life. (Credit: Roy Kaltschmidt/Berkeley Lab)

While studying Methanoperedens sampled from seasonal wetland pool soil in California, the scientists found evidence of an entirely new type of ECE. Unlike the circular strands of DNA that make up most plasmids, the most well-known type of extra-chromosomal element, the new ECEs are linear and very long – up to one-third the length of the entire Methanoperedens genome. After analyzing additional samples from underground soil, aquifers, and riverbeds in California and Colorado that contain methane-consuming archaea, the team uncovered a total of 19 distinct ECEs they dubbed “Borgs”. Using advanced genome analysis tools, the scientists determined that many of the sequences within the Borgs are similar to the methane-metabolizing genes within the actual Methanoperedens genome. Some of the Borgs even encode all the necessary cellular machinery to eat methane on their own, so long as they are inside a cell that can express the genes.

“Imagine a single cell that has the ability to consume methane. Now you add genetic elements within that cell that can consume methane in parallel and also add genetic elements that give the cell higher capacity. It basically creates a condition for methane consumption on steroids, if you will,” explained co-author Kenneth Williams, a senior scientist and Banfield’s colleague in Berkeley Lab’s Earth and Environmental Sciences Area. Williams led research at the Rifle, Colorado site where the best characterized Borg was recovered, and is also chief field scientist of a research site on the East River, near Crested Butte, Colorado, where some of Banfield’s current sampling takes place.

The East River field site is part of the Department of Energy’s Watershed Function Scientific Focus Area, a multidisciplinary research project led by Berkeley Lab that aims to link microbiology and biochemistry with hydrology and climate science. “Our expertise is bringing together what are often thought of and treated as completely disparate fields of inquiry – big science that links everything from genes all the way up to watershed and atmospheric processes.”

Resistance is futile a disadvantage

Banfield and her fellow researchers at UC Berkeley’s Innovative Genomics Institute, including co-author and longtime collaborator Jennifer Doudna, hypothesize that the Borgs could be residual fragments of entire microbes that were engulfed by Methanoperedens to aid metabolism, similar to how plant cells harnessed formerly free-living photosynthetic microbes to gain what we now call chloroplasts, and how an ancient eukaryotic cell consumed the ancestors of today’s mitochondria. Based on the similarities in sequences, the engulfed cell could have been a relative of Methanoperedens, but the overall diversity of genes found in the Borgs indicates that these DNA packages were assimilated from a wide range of organisms.

No matter the origin, it is clear that Borgs have existed alongside these archaea, shuttling genes back and forth, for a very long time.

Notably, some Methanoperedens were found with no Borgs. And, in addition to recognizable genes, the Borgs also contain unique genes encoding other metabolic proteins, membrane proteins, and extracellular proteins almost certainly involved in electron conduction required for energy generation, as well as other proteins that have unknown effects on their hosts. Until the scientists can culture Methanoperedens in a laboratory environment, they won’t know for sure what capabilities the different Borgs confer, why some microbes use them, and why others don’t.

One likely explanation is that Borgs act as a storage locker for metabolic genes that are only needed at certain times. Ongoing methane monitoring research has shown that methane concentrations can vary significantly throughout the year, usually peaking in the fall and dropping to the lowest levels in early spring. The Borgs therefore provide a competitive advantage to methane-eating microbes like Methanoperedens during periods of abundance when there is more methane than their native cellular machinery can break down.

Plasmids are known to serve a similar purpose, quickly spreading genes for resistance to toxic molecules (like heavy metals and antibiotics) when the toxins are present in high enough concentrations to exert evolutionary pressure.

“There is evidence that different types of Borgs sometimes coexist in the same host Methanopreredens cell. This opens the possibility that Borgs could be spreading genes across lineages,” said Banfield.

Boldly exploring the (microbial) universe

Since posting their article as a pre-print last year, the team has begun follow-up work to better understand how Borgs may affect biological and geological processes. Some researchers are combing through data sets of genetic material from other microorganisms, looking for evidence that Borgs exist in association with other species.

While her colleagues are using lab-based methods, co-author Susan Mullen, a graduate student in Banfield’s lab, will be getting her feet wet with some very picturesque field work. She recently started a project to sample microbes from the floodplains of the East River throughout the year to assess how seasonal changes in Borg abundance and other microbes known to be involved in methane cycling correlate to seasonal fluxes of methane.

According to the authors, years down the line, carefully cultured microbes chock full of Borgs could be used to reduce methane and curb global warming. It’s all to benefit the collective – life on Earth.

Science paper:
Nature
See the science paper for detailed material with images.

See the full article here .

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

Please help promote STEM in your local schools.

Stem Education Coalition

LBNL campus

Bringing Science Solutions to the World

In the world of science, The Lawrence Berkeley National Laboratory (Berkeley Lab) is synonymous with “excellence.” Thirteen Nobel prizes are associated with Berkeley Lab. Seventy Lab scientists are members of the The National Academy of Sciences, one of the highest honors for a scientist in the United States. Thirteen of our scientists have won the National Medal of Science, our nation’s highest award for lifetime achievement in fields of scientific research. Eighteen of our engineers have been elected to the The National Academy of Engineering, and three of our scientists have been elected into the Institute of Medicine. In addition, Berkeley Lab has trained thousands of university science and engineering students who are advancing technological innovations across the nation and around the world.

Berkeley Lab is a member of the national laboratory system supported by the U.S. Department of Energy through its Office of Science. It is managed by the University of California and is charged with conducting unclassified research across a wide range of scientific disciplines. Located on a 202-acre site in the hills above the University of California- Berkeley campus that offers spectacular views of the San Francisco Bay, Berkeley Lab employs approximately 3,232 scientists, engineers and support staff. The Lab’s total costs for FY 2014 were $785 million. A recent study estimates the Laboratory’s overall economic impact through direct, indirect and induced spending on the nine counties that make up the San Francisco Bay Area to be nearly $700 million annually. The Lab was also responsible for creating 5,600 jobs locally and 12,000 nationally. The overall economic impact on the national economy is estimated at $1.6 billion a year. Technologies developed at Berkeley Lab have generated billions of dollars in revenues, and thousands of jobs. Savings as a result of Berkeley Lab developments in lighting and windows, and other energy-efficient technologies, have also been in the billions of dollars.

Berkeley Lab was founded in 1931 by Ernest Orlando Lawrence, a University of California-Berkeley physicist who won the 1939 Nobel Prize in physics for his invention of the cyclotron, a circular particle accelerator that opened the door to high-energy physics. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab legacy that continues today.

History

1931–1941

The laboratory was founded on August 26, 1931, by Ernest Lawrence, as the Radiation Laboratory of the University of California-Berkeley, associated with the Physics Department. It centered physics research around his new instrument, the cyclotron, a type of particle accelerator for which he was awarded the Nobel Prize in Physics in 1939.

E.O. Lawrence’ first cyclotron.

LBNL 88 inch cyclotron.

LBNL 88 inch cyclotron.

Throughout the 1930s, Lawrence pushed to create larger and larger machines for physics research, courting private philanthropists for funding. He was the first to develop a large team to build big projects to make discoveries in basic research. Eventually these machines grew too large to be held on the university grounds, and in 1940 the lab moved to its current site atop the hill above campus. Part of the team put together during this period includes two other young scientists who went on to establish large laboratories; J. Robert Oppenheimer founded The DOE’s Los Alamos Laboratory, and Robert Wilson founded The DOE’s Fermi National Accelerator Laboratory.

1942–1950

Leslie Groves visited Lawrence’s Radiation Laboratory in late 1942 as he was organizing the Manhattan Project, meeting J. Robert Oppenheimer for the first time. Oppenheimer was tasked with organizing the nuclear bomb development effort and founded today’s Los Alamos National Laboratory to help keep the work secret. At the RadLab, Lawrence and his colleagues developed the technique of electromagnetic enrichment of uranium using their experience with cyclotrons. The “calutrons” (named after the University) became the basic unit of the massive Y-12 facility in Oak Ridge, Tennessee. Lawrence’s lab helped contribute to what have been judged to be the three most valuable technology developments of the war (the atomic bomb, proximity fuse, and radar). The cyclotron, whose construction was stalled during the war, was finished in November 1946. The Manhattan Project shut down two months later.

1951–2018

After the war, the Radiation Laboratory became one of the first laboratories to be incorporated into the Atomic Energy Commission (AEC) (now The Department of Energy . The most highly classified work remained at Los Alamos, but the RadLab remained involved. Edward Teller suggested setting up a second lab similar to Los Alamos to compete with their designs. This led to the creation of an offshoot of the RadLab (now The DOE’s Lawrence Livermore National Laboratory) in 1952. Some of the RadLab’s work was transferred to the new lab, but some classified research continued at Berkeley Lab until the 1970s, when it became a laboratory dedicated only to unclassified scientific research.

Shortly after the death of Lawrence in August 1958, the UC Radiation Laboratory (both branches) was renamed the Lawrence Radiation Laboratory. The Berkeley location became the Lawrence Berkeley Laboratory in 1971, although many continued to call it the RadLab. Gradually, another shortened form came into common usage, LBNL. Its formal name was amended to Ernest Orlando Lawrence Berkeley National Laboratory in 1995, when “National” was added to the names of all DOE labs. “Ernest Orlando” was later dropped to shorten the name. Today, the lab is commonly referred to as “Berkeley Lab”.

The Alvarez Physics Memos are a set of informal working papers of the large group of physicists, engineers, computer programmers, and technicians led by Luis W. Alvarez from the early 1950s until his death in 1988. Over 1700 memos are available on-line, hosted by the Laboratory.

The lab remains owned by the Department of Energy , with management from the University of California. Companies such as Intel were funding the lab’s research into computing chips.

Science mission

From the 1950s through the present, Berkeley Lab has maintained its status as a major international center for physics research, and has also diversified its research program into almost every realm of scientific investigation. Its mission is to solve the most pressing and profound scientific problems facing humanity, conduct basic research for a secure energy future, understand living systems to improve the environment, health, and energy supply, understand matter and energy in the universe, build and safely operate leading scientific facilities for the nation, and train the next generation of scientists and engineers.

The Laboratory’s 20 scientific divisions are organized within six areas of research: Computing Sciences; Physical Sciences; Earth and Environmental Sciences; Biosciences; Energy Sciences; and Energy Technologies. Berkeley Lab has six main science thrusts: advancing integrated fundamental energy science; integrative biological and environmental system science; advanced computing for science impact; discovering the fundamental properties of matter and energy; accelerators for the future; and developing energy technology innovations for a sustainable future. It was Lawrence’s belief that scientific research is best done through teams of individuals with different fields of expertise, working together. His teamwork concept is a Berkeley Lab tradition that continues today.

Berkeley Lab operates five major National User Facilities for the DOE Office of Science:

The Advanced Light Source (ALS) is a synchrotron light source with 41 beam lines providing ultraviolet, soft x-ray, and hard x-ray light to scientific experiments.

The DOE’s Lawrence Berkeley National Laboratory Advanced Light Source.
The ALS is one of the world’s brightest sources of soft x-rays, which are used to characterize the electronic structure of matter and to reveal microscopic structures with elemental and chemical specificity. About 2,500 scientist-users carry out research at ALS every year. Berkeley Lab is proposing an upgrade of ALS which would increase the coherent flux of soft x-rays by two-three orders of magnitude.

Berkeley Lab Laser Accelerator (BELLA) Center

A view of BELLA, the Berkeley Lab Laser Accelerator. Credit: Roy Kaltschmidt-Berkeley Lab.

The DOE Joint Genome Institute supports genomic research in support of the DOE missions in alternative energy, global carbon cycling, and environmental management. The JGI’s partner laboratories are Berkeley Lab, DOE’s Lawrence Livermore National Laboratory, DOE’s Oak Ridge National Laboratory (ORNL), DOE’s Pacific Northwest National Laboratory (PNNL), and the HudsonAlpha Institute for Biotechnology . The JGI’s central role is the development of a diversity of large-scale experimental and computational capabilities to link sequence to biological insights relevant to energy and environmental research. Approximately 1,200 scientist-users take advantage of JGI’s capabilities for their research every year.

LBNL Molecular Foundry

The LBNL Molecular Foundry is a multidisciplinary nanoscience research facility. Its seven research facilities focus on Imaging and Manipulation of Nanostructures; Nanofabrication; Theory of Nanostructured Materials; Inorganic Nanostructures; Biological Nanostructures; Organic and Macromolecular Synthesis; and Electron Microscopy. Approximately 700 scientist-users make use of these facilities in their research every year.

The DOE’s NERSC National Energy Research Scientific Computing Center is the scientific computing facility that provides large-scale computing for the DOE’s unclassified research programs. Its current systems provide over 3 billion computational hours annually. NERSC supports 6,000 scientific users from universities, national laboratories, and industry.

DOE’s NERSC National Energy Research Scientific Computing Center at Lawrence Berkeley National Laboratory.

Cray Cori II supercomputer at National Energy Research Scientific Computing Center at DOE’s Lawrence Berkeley National Laboratory, named after Gerty Cori, the first American woman to win a Nobel Prize in science.

NERSC Hopper Cray XE6 supercomputer.

NERSC Cray XC30 Edison supercomputer.

NERSC GPFS for Life Sciences.

The Genepool system is a cluster dedicated to the DOE Joint Genome Institute’s computing needs. Denovo is a smaller test system for Genepool that is primarily used by NERSC staff to test new system configurations and software.

NERSC PDSF computer cluster in 2003.

PDSF is a networked distributed computing cluster designed primarily to meet the detector simulation and data analysis requirements of physics, astrophysics and nuclear science collaborations.

Cray Shasta Perlmutter SC18 AMD Epyc Nvidia pre-exascale supercomputer.

NERSC is a DOE Office of Science User Facility.

The DOE’s Energy Science Network is a high-speed network infrastructure optimized for very large scientific data flows. ESNet provides connectivity for all major DOE sites and facilities, and the network transports roughly 35 petabytes of traffic each month.

Berkeley Lab is the lead partner in the DOE’s Joint Bioenergy Institute (JBEI), located in Emeryville, California. Other partners are the DOE’s Sandia National Laboratory, the University of California (UC) campuses of Berkeley and Davis, the Carnegie Institution for Science , and DOE’s Lawrence Livermore National Laboratory (LLNL). JBEI’s primary scientific mission is to advance the development of the next generation of biofuels – liquid fuels derived from the solar energy stored in plant biomass. JBEI is one of three new U.S. Department of Energy (DOE) Bioenergy Research Centers (BRCs).

Berkeley Lab has a major role in two DOE Energy Innovation Hubs. The mission of the Joint Center for Artificial Photosynthesis (JCAP) is to find a cost-effective method to produce fuels using only sunlight, water, and carbon dioxide. The lead institution for JCAP is the California Institute of Technology and Berkeley Lab is the second institutional center. The mission of the Joint Center for Energy Storage Research (JCESR) is to create next-generation battery technologies that will transform transportation and the electricity grid. DOE’s Argonne National Laboratory leads JCESR and Berkeley Lab is a major partner.

From The University of New South Wales (AU) : “World wide web – global spider silk database a boon for biomaterials”

From The University of New South Wales (AU)

10.14.22
Lachlan Gilbert

A new global study has untangled many of the incredible properties of spider silk.

Cyrtophora moluccensis, also known as the dome tent spider, is about the width of a man’s hand and is part of the orb-weaver family. Photo: UNSW/Sean Blamires.

What’s stronger and tougher than steel, and more elastic than rubber, weight for weight? Spider silk is, and this incredibly versatile material could transform engineering, materials science and even medicine – if we could just work out how to produce it.

Now a new global study that has catalogued web silk properties of almost 1100 spiders hopes to provide a launchpad for the design of future biomaterials that emulate this wonder of nature.

Dr Sean Blamires, an evolutionary ecological biologist from UNSW Sydney’s School of Biological, Environmental and Earth Sciences, says the new research, which was published recently in the journal Science Advances [below], examined the chemical structure, the genetics and the particular way that each spider spins their webs and marked these against the physical properties of the silk.

The team of researchers that spanned Asia, Oceania, Europe and the US spent five years collecting spiders from around the world, observing them, extracting silk and sequencing their transcriptomes – the RNA molecules that are coded to make silk. They added a massive dataset to the existing knowledge base which was previously limited to 52 species of spiders in 18 families, with 1098 new species from 76 families.

The Tasmanian Cave Spider is large and weaves a web that may be more than a metre wide. Photo: UNSW/Sean Blamires.

“Up until now there was a pretty good literature set of how spider silk performs, and we’ve seen some good genetic analysis as well with some whole silk transcriptomes mapped out on three or four species,” says Dr Blamires.

“But what has been lacking is a way to generalize across spiders and find out what actually causes specific properties. Is there a link between genes, protein structures and fibres?

“By combining so many species and so many individual samples, it becomes possible to perform some complex models using machine learning to help understand what’s happening at every level. Also, how and why you get specific properties for some silks which not only vary greatly between species, but can even vary between individuals.”

Nephila spiders, also known as golden orb-weavers, are known to capture birds and snakes in their webs. Photo: UNSW/Sean Blamires.

Dragline silk

There are seven types of spider silk and one of them has caught scientists’ imagination for decades for its strength, durability and flexibility: dragline silk.

“We focused on a specific silk called major ambulate silk or dragline silk,” says Dr Blamires.

“In a spiderweb, the dragline silk makes up the framework and the radials. It’s also the silk that the spider uses when it drops off a web. Non-web building spiders might use it to make retreats or use it for signalling with each other, while trapdoor spiders use something very similar.”

He says the reason for the interest in dragline silk is that in certain spiders like orb-weaving spiders, it’s extremely tough and outperforms Kevlar and steel. But in addition to its hardness, it is flexible.

“So it’s rubbery and tough at the same time, while most other materials are either one or the other.”

Argiope keyserlingi, known commonly as a St Andrew’s cross spider, is a species of orb-web spider found on the east coast of Australia, from Victoria to northern Queensland. Photo: UNSW/Sean Blamires.

This is the quality that has made it so attractive as a biomaterial to emulate in technological applications. Suggested uses have included a lightweight material to use in bulletproof vests, a flexible building material, biodegradable bottles, or as a non-toxic biomaterial in regenerative medicine that can be used as a kind of scaffold to grow and repair damaged nerves or tissues.

But what is it about spiderweb silk that makes it so different from most other organic and inorganic materials?

Dr Blamires says this is the question that has fascinated humanity for hundreds of years.

“Spider silk is basically made up of proteins called “spidroins”. We know spiders secrete it from a gland, but how this contributes to its toughness and flexibility, and even the way it is stored in the gland before being secreted, is still somewhat of a mystery. If we want to produce it, we need to understand it.

“And even then, understanding how the spider does it is one step, the next is replicating something similar, possibly using microfluidic technology in a lab.”

Which is where the database of the 1100 spider silk transcriptomes will be so useful to biologists, material scientists and engineers.

“Just like the Human Genome project has given researchers the ability to identify specific gene sequence mutations that cause specific diseases, this database and the accompanying structure-function analyses gives biologists and material scientists the ability to derive direct genetic causes for the properties of spider silk,” Dr Blamires says.

Science paper:
Science Advances
See the science paper for detailed material with images.

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 New South Wales is an Australian public university with its largest campus in the Sydney suburb of Kensington.

Established in 1949, UNSW is a research university, ranked 44th in the world in the 2021 QS World University Rankings and 67th in the world in the 2021 Times Higher Education World University Rankings. UNSW is one of the founding members of the Group of Eight, a coalition of Australian research-intensive universities, and of Universitas 21, a global network of research universities. It has international exchange and research partnerships with over 200 universities around the world.

According to the 2021 QS World University Rankings by Subject, UNSW is ranked top 20 in the world for Law, Accounting and Finance, and 1st in Australia for Mathematics, Engineering and Technology. UNSW also leads Australia in Medicine, where the median ATAR (Australian university entrance examination results) of its Medical School students is higher than any other Australian medical school. UNSW enrolls the highest number of Australia’s top 500 high school students academically, and produces more millionaire graduates than any other Australian university.

The university comprises seven faculties, through which it offers bachelor’s, master’s and doctoral degrees. The main campus is in the Sydney suburb of Kensington, 7 kilometres (4.3 mi) from the Sydney CBD. The creative arts faculty, UNSW Art & Design, is located in Paddington, and subcampuses are located in the Sydney CBD as well as several other suburbs, including Randwick and Coogee. Research stations are located throughout the state of New South Wales.

The university’s second largest campus, known as UNSW Canberra at ADFA (formerly known as UNSW at ADFA), is situated in Canberra, in the Australian Capital Territory (ACT). ADFA is the military academy of the Australian Defense Force, and UNSW Canberra is the only national academic institution with a defense focus.

Research centres

The university has a number of purpose-built research facilities, including:

UNSW Lowy Cancer Research Centre is Australia’s first facility bringing together researchers in childhood and adult cancers, as well as one of the country’s largest cancer-research facilities, housing up to 400 researchers.
The Mark Wainwright Analytical Centre is a centre for the faculties of science, medicine, and engineering. It is used to study the structure and composition of biological, chemical, and physical materials.
UNSW Canberra Cyber is a cyber-security research and teaching centre.
The Sino-Australian Research Centre for Coastal Management (SARCCM) has a multidisciplinary focus, and works collaboratively with the Ocean University of China [中國海洋大學](CN) in coastal management research.