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  • richardmitnick 12:11 pm on December 5, 2022 Permalink | Reply
    Tags: "In Ironic Twist CRISPR System Used to Befuddle Bacteria", A CRISPR conundrum, A mechanism to aid the microbiome, , Bacteria use CRISPR-Cas systems as adaptive immune systems to withstand attacks from enemies like viruses., , , DNA, , , , Viruses engineered with a CRISPR-Cas system can thwart bacterial defenses and make selective changes to a targeted bacterium.   

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

    NC State bloc

    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

    1
    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.
    2
    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.
    3
    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

    NC State campus

    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.

     
  • richardmitnick 11:35 am on December 5, 2022 Permalink | Reply
    Tags: "How to Edit the Genes of Nature’s Master Manipulators", A CRISPR-Cas system consists of short snippets of RNA that are complementary to sequences in phage genes., , Bacteriophages are some of the most abundant and diverse biological entities on Earth., , CRISPR-Cas is a type of immune defense mechanism that many bacteria and archaea use against phages., CRISPR-Cas13, CRISPR-the Nobel Prize-winning gene editing technology-is poised to have a profound impact on the fields of microbiology and medicine yet again., DNA, , , , , Jill Banfield, , , , Scientists are using CRISPR to engineer the viruses that evolved to engineer bacteria., , The phage-fighting potency of CRISPR-Cas13 was unexpected given how few microbes use it.   

    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.

    1
    (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.
    2
    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.
    3
    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!”

    4
    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

    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.

    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

    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.

     
  • richardmitnick 8:31 am on November 30, 2022 Permalink | Reply
    Tags: "New CRISPR-based tool inserts large DNA sequences at desired sites in cells", "PASTE": Programmable Addition via Site-specific Targeting Elements, , , , DNA, For this study the researchers focused on "serine integrases" which can insert huge chunks of DNA-as large as 50000 base pairs., , , , The ability to site-specifically make large genomic integrations is of huge value to both basic science and biotechnology studies., 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., The DNA sequences that the researchers inserted in this study were up to 36000 base pairs long but they believe even longer sequences could also be used., , 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.   

    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

    1
    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

    MIT Seal

    USPS “Forever” postage stamps celebrating Innovation at MIT.

    MIT Campus

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

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

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

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

    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.

     
  • richardmitnick 11:04 am on October 9, 2022 Permalink | Reply
    Tags: "Biologists glean insight into repetitive protein sequences", "LCRs": “low-complexity regions”, , , DNA, , ,   

    From The Massachusetts Institute of Technology: “Biologists glean insight into repetitive protein sequences” 

    From The Massachusetts Institute of Technology

    September 13, 2022 [Just found this.]
    Anne Trafton

    A computational analysis reveals that many repetitive sequences are shared across proteins and are similar in species from bacteria to humans.

    1
    MIT researchers used a technique called dot-plot matrix, which is a way to visually represent amino acid sequences, to compare protein sequences known as “low-complexity regions” across many different species. Image: Courtesy of the researchers, and edited by MIT News.

    2
    Using computational analysis, researchers have found that many repetitive sequences are shared across proteins and are similar in species from bacteria to humans. Courtesy of the researchers.

    About 70 percent of all human proteins include at least one sequence consisting of a single amino acid repeated many times, with a few other amino acids sprinkled in. These “low-complexity regions” are also found in most other organisms.

    The proteins that contain these sequences have many different functions, but MIT biologists have now come up with a way to identify and study them as a unified group. Their technique allows them to analyze similarities and differences between LCRs from different species, and helps them to determine the functions of these sequences and the proteins in which they are found.

    Using their technique, the researchers have analyzed all of the proteins found in eight different species, from bacteria to humans. They found that while LCRs can vary between proteins and species, they often share a similar role — helping the protein in which they’re found to join a larger-scale assembly such as the nucleolus, an organelle found in nearly all human cells.

    “Instead of looking at specific LCRs and their functions, which might seem separate because they’re involved in different processes, our broader approach allows us to see similarities between their properties, suggesting that maybe the functions of LCRs aren’t so disparate after all,” says Byron Lee, an MIT graduate student.

    The researchers also found some differences between LCRs of different species and showed that these species-specific LCR sequences correspond to species-specific functions, such as forming plant cell walls.

    Lee and graduate student Nima Jaberi-Lashkari are the lead authors of the study, which appears today in eLife [below]. Eliezer Calo, an assistant professor of biology at MIT, is the senior author of the paper.

    Large-scale study

    Previous research has revealed that LCRs are involved in a variety of cellular processes, including cell adhesion and DNA binding. These LCRs are often rich in a single amino acid such as alanine, lysine, or glutamic acid.

    Finding these sequences and then studying their functions individually is a time-consuming process, so the MIT team decided to use bioinformatics — an approach that uses computational methods to analyze large sets of biological data — to evaluate them as a larger group.

    “What we wanted to do is take a step back and instead of looking at individual LCRs, to try to take a look at all of them and to see if we could observe some patterns on a larger scale that might help us figure out what the ones that have assigned functions are doing, and also help us learn a bit about what the ones that don’t have assigned functions are doing,” Jaberi-Lashkari says.

    To do that, the researchers used a technique called dotplot matrix, which is a way to visually represent amino acid sequences, to generate images of each protein under study. They then used computational image processing methods to compare thousands of these matrices at the same time.

    Using this technique, the researchers were able to categorize LCRs based on which amino acids were most frequently repeated in the LCR. They also grouped LCR-containing proteins by the number of copies of each LCR type found in the protein. Analyzing these traits helped the researchers to learn more about the functions of these LCRs.

    As one demonstration, the researchers picked out a human protein, known as RPA43, that has three lysine-rich LCRs. This protein is one of many subunits that make up an enzyme called RNA polymerase 1, which synthesizes ribosomal RNA. The researchers found that the copy number of lysine-rich LCRs is important for helping the protein integrate into the nucleolus, the organelle responsible for synthesizing ribosomes.

    Biological assemblies

    In a comparison of the proteins found in eight different species, the researchers found that some LCR types are highly conserved between species, meaning that the sequences have changed very little over evolutionary timescales. These sequences tend to be found in proteins and cell structures that are also highly conserved, such as the nucleolus.

    “These sequences seem to be important for the assembly of certain parts of the nucleolus,” Lee says. “Some of the principles that are known to be important for higher order assembly seem to be at play because the copy number, which might control how many interactions a protein can make, is important for the protein to integrate into that compartment.”

    The researchers also found differences between LCRs seen in two different types of proteins that are involved in nucleolus assembly. They discovered that a nucleolar protein known as TCOF contains many glutamine-rich LCRs that can help scaffold the formation of assemblies, while nucleolar proteins with only a few of these glutamic acid-rich LCRs could be recruited as clients (proteins that interact with the scaffold).

    Another structure that appears to have many conserved LCRs is the nuclear speckle, which is found inside the cell nucleus. The researchers also found many similarities between LCRs that are involved in forming larger-scale assemblies such as the extracellular matrix, a network of molecules that provides structural support to cells in plants and animals.

    The research team also found examples of structures with LCRs that seem to have diverged between species. For example, plants have distinctive LCR sequences in the proteins that they use to scaffold their cell walls, and these LCRs are not seen in other types of organisms.

    The researchers now plan to expand their LCR analysis to additional species.

    “There’s so much to explore, because we can expand this map to essentially any species,” Lee says. “That gives us the opportunity and the framework to identify new biological assemblies.”

    The research was funded by the National Institute of General Medical Sciences, National Cancer Institute, the Ludwig Center at MIT, a National Institutes of Health Pre-Doctoral Training Grant, and the Pew Charitable Trusts.

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

    See the full article here .


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    MIT Seal

    USPS “Forever” postage stamps celebrating Innovation at MIT.

    MIT Campus

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

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

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

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

    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.

     
  • richardmitnick 10:52 am on August 21, 2022 Permalink | Reply
    Tags: "See How Scientists Put Together the Complete Human Genome?", , , , DNA, For the first time researchers have sequenced all 3117275501 bases of our genetic code., ,   

    From “Scientific American” : “See How Scientists Put Together the Complete Human Genome” 

    From “Scientific American”

    8.1.22
    Clara Moskowitz
    Martin Krzywinski

    For the first time researchers have sequenced all 3117275501 bases of our genetic code.

    1
    Credit: Martin Krzywinski.

    The human genome is at last complete. Researchers have been working for decades toward this goal, and the Human Genome Project claimed victory in 2001, when it had read almost all of a person’s DNA. But the stubborn remaining 8 percent of the genome took another two decades to decipher. These final sections were highly repetitive and highly variable among individuals, making them the hardest parts to sequence. Yet they revealed hundreds of new genes, including genes involved in immune responses and those responsible for humans developing larger brains than our primate ancestors. “Now that we have one complete reference, we can understand human variation and how we changed with respect to our closest related species on the planet,” says geneticist Evan Eichler of the University of Washington, one of the co-chairs of the Telomere-to-Telomere consortium at The National Human Genome Research Institute that finished the genome.


    Credit: Martin Krzywinski; Sources: The University of California-Santa Cruz Genome Browser; “The Complete Sequence of a Human Genome,” by Sergey Nurk et al., in Science April 2022.

    See the full article here .


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    Scientific American, the oldest continuously published magazine in the U.S., has been bringing its readers unique insights about developments in science and technology for more than 160 years.

     
  • richardmitnick 7:55 am on July 17, 2022 Permalink | Reply
    Tags: , , , , , DNA, , , Scientists created a family tree that allowed them to reconstruct rhodopsins from 2.5 to 4 billion years ago and the conditions that they likely faced., Scientists have reconstructed what life was like for some of Earth’s earliest organisms., ,   

    From The University of California-Riverside: “Ancient microbes may help us find extraterrestrial life forms” 

    UC Riverside bloc

    From The University of California-Riverside

    June 27, 2022
    Jules Bernstein

    Using light-capturing proteins in living microbes, scientists have reconstructed what life was like for some of Earth’s earliest organisms. These efforts could help us recognize signs of life on other planets, whose atmospheres may more closely resemble our pre-oxygen planet.

    2
    Earth of billions of years ago illuminated by light-capturing proteins.
    Rendering of the process by which ancient microbes captured light with rhodopsin proteins. (Sohail Wasif/UCR)

    The earliest living things, including bacteria and single-celled organisms called archaea, inhabited a primarily oceanic planet without an ozone layer to protect them from the sun’s radiation. These microbes evolved rhodopsins — proteins with the ability to turn sunlight into energy, using them to power cellular processes.

    “On early Earth, energy may have been very scarce. Bacteria and archaea figured out how to use the plentiful energy from the sun without the complex biomolecules required for photosynthesis,” said UC Riverside astrobiologist Edward Schwieterman, who is co-author of a study describing the research.

    Rhodopsins are related to rods and cones in human eyes that enable us to distinguish between light and dark and see colors. They are also widely distributed among modern organisms and environments like saltern ponds, which present a rainbow of vibrant colors.

    Using machine learning the research team analyzed rhodopsin protein sequences from all over the world and tracked how they evolved over time. Then, they created a type of family tree that allowed them to reconstruct rhodopsins from 2.5 to 4 billion years ago, and the conditions that they likely faced.

    “Life as we know it is as much an expression of the conditions on our planet as it is of life itself. We resurrected ancient DNA sequences of one molecule, and it allowed us to link to the biology and environment of the past,” said University of Wisconsin-Madison astrobiologist and study lead Betul Kacar.

    “It’s like taking the DNA of many grandchildren to reproduce the DNA of their grandparents. Only, it’s not grandparents, but tiny things that lived billions of years ago, all over the world,” Schwieterman said.

    Modern rhodopsins absorb blue, green, yellow and orange light, and can appear pink, purple or red by virtue of the light they are not absorbing or complementary pigments. However, according to the team’s reconstructions, ancient rhodopsins were tuned to absorb mainly blue and green light.

    Since ancient Earth did not yet have the benefit of an ozone layer, the research team theorizes that billions-of-years-old microbes lived many meters down in the water column to shield themselves from intense UVB radiation at the surface.

    Blue and green light best penetrates water, so it is likely that the earliest rhodopsins primarily absorbed these colors. “This could be the best combination of being shielded and still being able to absorb light for energy,” Schwieterman said.

    After the Great Oxidation Event, more than 2 billion years ago, Earth’s atmosphere began to experience a rise in the amount of oxygen. With additional oxygen and ozone in the atmosphere, rhodopsins evolved to absorb additional colors of light.

    Rhodopsins today are able to absorb colors of light that chlorophyll pigments in plants cannot. Though they represent completely unrelated and independent light capture mechanisms, they absorb complementary areas of the spectrum.

    “This suggests co-evolution, in that one group of organisms is exploiting light not absorbed by the other,” Schwieterman said. “This could have been because rhodopsins developed first and screened out the green light, so chlorophylls later developed to absorb the rest. Or it could have happened the other way around.”

    Moving forward, the team is hoping to resurrect model rhodopsins in a laboratory using synthetic biology techniques.

    “We engineer the ancient DNA inside modern genomes and reprogram the bugs to behave how we believe they did millions of years ago. Rhodopsin is a great candidate for laboratory time-travel studies,” Kacar said.

    Ultimately, the team is pleased about the possibilities for research opened up by techniques they used for this study. Since other signs of life from the deep geologic past need to be physically preserved and only some molecules are amenable to long-term preservation, there are many aspects of life’s history that have not been accessible to researchers until now.

    “Our study demonstrates for the first time that the behavioral histories of enzymes are amenable to evolutionary reconstruction in ways that conventional molecular biosignatures are not,” Kacar said.

    The team also hopes to take what they learned about the behavior of early Earth organisms and use it to search the skies for signs of life on other planets.

    “Early Earth is an alien environment compared to our world today. Understanding how organisms here have changed with time and in different environments is going to teach us crucial things about how to search for and recognize life elsewhere,” Schwieterman said.

    The findings are detailed in a paper published in the journal Molecular Biology and Evolution.

    See the full article here .

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    University of California-Riverside Campus

    The University of California-Riverside is a public land-grant research university in Riverside, California. It is one of the 10 campuses of The University of California system. The main campus sits on 1,900 acres (769 ha) in a suburban district of Riverside with a branch campus of 20 acres (8 ha) in Palm Desert. In 1907, the predecessor to The University of California-Riverside was founded as the UC Citrus Experiment Station, Riverside which pioneered research in biological pest control and the use of growth regulators responsible for extending the citrus growing season in California from four to nine months. Some of the world’s most important research collections on citrus diversity and entomology, as well as science fiction and photography, are located at Riverside.

    The University of California-Riverside ‘s undergraduate College of Letters and Science opened in 1954. The Regents of the University of California declared The University of California-Riverside a general campus of the system in 1959, and graduate students were admitted in 1961. To accommodate an enrollment of 21,000 students by 2015, more than $730 million has been invested in new construction projects since 1999. Preliminary accreditation of the The University of California-Riverside School of Medicine was granted in October 2012 and the first class of 50 students was enrolled in August 2013. It is the first new research-based public medical school in 40 years.

    The University of California-Riverside is classified among “R1: Doctoral Universities – Very high research activity.” The 2019 U.S. News & World Report Best Colleges rankings places UC-Riverside tied for 35th among top public universities and ranks 85th nationwide. Over 27 of The University of California-Riverside ‘s academic programs, including the Graduate School of Education and the Bourns College of Engineering, are highly ranked nationally based on peer assessment, student selectivity, financial resources, and other factors. Washington Monthly ranked The University of California-Riverside 2nd in the United States in terms of social mobility, research and community service, while U.S. News ranks The University of California-Riverside as the fifth most ethnically diverse and, by the number of undergraduates receiving Pell Grants (42 percent), the 15th most economically diverse student body in the nation. Over 70% of all The University of California-Riverside students graduate within six years without regard to economic disparity. The University of California-Riverside ‘s extensive outreach and retention programs have contributed to its reputation as a “university of choice” for minority students. In 2005, The University of California-Riverside became the first public university campus in the nation to offer a gender-neutral housing option. The University of California-Riverside’s sports teams are known as the Highlanders and play in the Big West Conference of the National Collegiate Athletic Association (NCAA) Division I. Their nickname was inspired by the high altitude of the campus, which lies on the foothills of Box Springs Mountain. The University of California-Riverside women’s basketball team won back-to-back Big West championships in 2006 and 2007. In 2007, the men’s baseball team won its first conference championship and advanced to the regionals for the second time since the university moved to Division I in 2001.

    History

    At the turn of the 20th century, Southern California was a major producer of citrus, the region’s primary agricultural export. The industry developed from the country’s first navel orange trees, planted in Riverside in 1873. Lobbied by the citrus industry, the University of California Regents established the UC Citrus Experiment Station (CES) on February 14, 1907, on 23 acres (9 ha) of land on the east slope of Mount Rubidoux in Riverside. The station conducted experiments in fertilization, irrigation and crop improvement. In 1917, the station was moved to a larger site, 475 acres (192 ha) near Box Springs Mountain.

    The 1944 passage of the GI Bill during World War II set in motion a rise in college enrollments that necessitated an expansion of the state university system in California. A local group of citrus growers and civic leaders, including many University of California-Berkeley alumni, lobbied aggressively for a University of California -administered liberal arts college next to the CES. State Senator Nelson S. Dilworth authored Senate Bill 512 (1949) which former Assemblyman Philip L. Boyd and Assemblyman John Babbage (both of Riverside) were instrumental in shepherding through the State Legislature. Governor Earl Warren signed the bill in 1949, allocating $2 million for initial campus construction.

    Gordon S. Watkins, dean of the College of Letters and Science at The University of California-Los Angeles, became the first provost of the new college at Riverside. Initially conceived of as a small college devoted to the liberal arts, he ordered the campus built for a maximum of 1,500 students and recruited many young junior faculty to fill teaching positions. He presided at its opening with 65 faculty and 127 students on February 14, 1954, remarking, “Never have so few been taught by so many.”

    The University of California-Riverside’s enrollment exceeded 1,000 students by the time Clark Kerr became president of the University of California system in 1958. Anticipating a “tidal wave” in enrollment growth required by the baby boom generation, Kerr developed the California Master Plan for Higher Education and the Regents designated Riverside a general university campus in 1959. The University of California-Riverside’s first chancellor, Herman Theodore Spieth, oversaw the beginnings of the school’s transition to a full university and its expansion to a capacity of 5,000 students. The University of California-Riverside’s second chancellor, Ivan Hinderaker led the campus through the era of the free speech movement and kept student protests peaceful in Riverside. According to a 1998 interview with Hinderaker, the city of Riverside received negative press coverage for smog after the mayor asked Governor Ronald Reagan to declare the South Coast Air Basin a disaster area in 1971; subsequent student enrollment declined by up to 25% through 1979. Hinderaker’s development of innovative programs in business administration and biomedical sciences created incentive for enough students to enroll at University of California-Riverside to keep the campus open.

    In the 1990s, The University of California-Riverside experienced a new surge of enrollment applications, now known as “Tidal Wave II”. The Regents targeted The University of California-Riverside for an annual growth rate of 6.3%, the fastest in The University of California system, and anticipated 19,900 students at The University of California-Riverside by 2010. By 1995, African American, American Indian, and Latino student enrollments accounted for 30% of The University of California-Riverside student body, the highest proportion of any University of California campus at the time. The 1997 implementation of Proposition 209—which banned the use of affirmative action by state agencies—reduced the ethnic diversity at the more selective UC campuses but further increased it at The University of California-Riverside.

    With The University of California-Riverside scheduled for dramatic population growth, efforts have been made to increase its popular and academic recognition. The students voted for a fee increase to move The University of California-Riverside athletics into NCAA Division I standing in 1998. In the 1990s, proposals were made to establish a law school, a medical school, and a school of public policy at The University of California-Riverside, with The University of California-Riverside School of Medicine and the School of Public Policy becoming reality in 2012. In June 2006, The University of California-Riverside received its largest gift, 15.5 million from two local couples, in trust towards building its medical school. The Regents formally approved The University of California-Riverside’s medical school proposal in 2006. Upon its completion in 2013, it was the first new medical school built in California in 40 years.

    Academics

    As a campus of The University of California system, The University of California-Riverside is governed by a Board of Regents and administered by a president University of California-Riverside ‘s academic policies are set by its Academic Senate, a legislative body composed of all UC-Riverside faculty members.

    The University of California-Riverside is organized into three academic colleges, two professional schools, and two graduate schools. The University of California-Riverside’s liberal arts college, the College of Humanities, Arts and Social Sciences, was founded in 1954, and began accepting graduate students in 1960. The College of Natural and Agricultural Sciences, founded in 1960, incorporated the CES as part of the first research-oriented institution at The University of California-Riverside; it eventually also incorporated the natural science departments formerly associated with the liberal arts college to form its present structure in 1974. The University of California-Riverside ‘s newest academic unit, the Bourns College of Engineering, was founded in 1989. Comprising the professional schools are the Graduate School of Education, founded in 1968, and The University of California-Riverside School of Business, founded in 1970. These units collectively provide 81 majors and 52 minors, 48 master’s degree programs, and 42 Doctor of Philosophy (PhD) programs. The University of California-Riverside is the only UC campus to offer undergraduate degrees in creative writing and public policy and one of three UCs (along with The University of California-Berkeley and The University of California-Irvine) to offer an undergraduate degree in business administration. Through its Division of Biomedical Sciences, founded in 1974, The University of California-Riverside offers the Thomas Haider medical degree program in collaboration with The University of California-Los Angeles. The University of California-Riverside ‘s doctoral program in the emerging field of dance theory, founded in 1992, was the first program of its kind in the United States, and The University of California-Riverside ‘s minor in lesbian, gay and bisexual studies, established in 1996, was the first undergraduate program of its kind in the University of California system. A new BA program in bagpipes was inaugurated in 2007.

    Research and economic impact

    The University of California-Riverside operated under a $727 million budget in fiscal year 2014–15. The state government provided $214 million, student fees accounted for $224 million and $100 million came from contracts and grants. Private support and other sources accounted for the remaining $189 million. Overall, monies spent at The University of California-Riverside have an economic impact of nearly $1 billion in California. The University of California-Riverside research expenditure in FY 2018 totaled $167.8 million. Total research expenditures at The University of California-Riverside are significantly concentrated in agricultural science, accounting for 53% of total research expenditures spent by the university in 2002. Top research centers by expenditure, as measured in 2002, include the Agricultural Experiment Station; the Center for Environmental Research and Technology; the Center for Bibliographical Studies; the Air Pollution Research Center; and the Institute of Geophysics and Planetary Physics.

    Throughout The University of California-Riverside’s history, researchers have developed more than 40 new citrus varieties and invented new techniques to help the $960 million-a-year California citrus industry fight pests and diseases. In 1927, entomologists at the CES introduced two wasps from Australia as natural enemies of a major citrus pest, the citrophilus mealybug, saving growers in Orange County $1 million in annual losses. This event was pivotal in establishing biological control as a practical means of reducing pest populations. In 1963, plant physiologist Charles Coggins proved that application of gibberellic acid allows fruit to remain on citrus trees for extended periods. The ultimate result of his work, which continued through the 1980s, was the extension of the citrus-growing season in California from four to nine months. In 1980, The University of California-Riverside released the Oroblanco grapefruit, its first patented citrus variety. Since then, the citrus breeding program has released other varieties such as the Melogold grapefruit, the Gold Nugget mandarin (or tangerine), and others that have yet to be given trademark names.

    To assist entrepreneurs in developing new products, The University of California-Riverside is a primary partner in the Riverside Regional Technology Park, which includes the City of Riverside and the County of Riverside. It also administers six reserves of the University of California Natural Reserve System. UC-Riverside recently announced a partnership with China Agricultural University[中国农业大学](CN) to launch a new center in Beijing, which will study ways to respond to the country’s growing environmental issues. University of California-Riverside can also boast the birthplace of two-name reactions in organic chemistry, the Castro-Stephens coupling and the Midland Alpine Borane Reduction.

     
  • richardmitnick 6:56 am on July 6, 2022 Permalink | Reply
    Tags: "Making CRISPR hype more of a reality", , , DNA, , , ,   

    From The Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH): “Making CRISPR hype more of a reality” 

    From The Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH)

    7.6.22
    Dr. Eric Aird

    This year we celebrate 10 years of genome editing with CRISPR.

    1
    Scientific American/ Credit: Getty Images

    The system is often referred to as molecular scissors, and this designation is quite accurate for its first applications. These short 10 years were marked by stunningly swift development and a great promise to cure thousands of genetic diseases with relative ease – with a single treatment dose that specifically corrects disease-​causing DNA mutations in the body’s cells. Sickle cell anemia and muscular dystrophy are two such diseases. And indeed, a decade later, we are now delivering on that promise in the form of many therapies currently being tested in human clinical trials.

    Parallel to the development of the first such therapies, scientists have further evolved genome editing technologies. Recently developed molecular CRISPR tools have little in common with molecular scissors and are poised to make medical applications even safer.

    Let’s take a brief look back: “first generation” CRISPR genetic scissors dock at specific sites in the genome and cut the DNA molecule. The cell generates short, arbitrary mutations at the break site to, for example, disrupt gene function. However, unintended genetic alterations to the cell are possible, and the scope of diseases treatable with this methodology are relatively small. An ill-​intended cut in the genome might manifest itself as a trigger for cancer decades later. Additionally, these scissors cause DNA damage, and such damage is inherently toxic and potentially lethal for cells. Stem cells, a primary target for clinical uses of CRISPR, react particularly sensitively to DNA damage.

    A broad application of this first generation of CRISPR in humans is therefore not entirely risk-​free. This is also a major reason why scientists have developed molecular tools to generate genomic modifications without using scissors.

    In the past few years, researchers across the globe have developed a host of such “next generation” CRISPR technologies. A more appropriate analogy for these innovative systems would that be of a molecular taxi. Such platforms can be used to shuttle, for example, specialized proteins to specific destinations in the genome. These proteins can directly change the DNA code without the same deleterious consequences caused by scissors.

    Reduced toxicity

    Not only does this approach reduce toxicity for cells, but it also vastly expands the range of treatable genetic diseases. Instead of simply cutting a gene to render it non-​functional, these CRISPR genome editors1 can be used to correct individual genetic mutations to restore gene function. It is estimated that more than 100,000 DNA mutations in our genome cause disease, a vast majority of which could be treated with such new technologies.

    Next generation genome editing systems are expected to be used in human trials for the first time later this year. An American biotech company recently received approval to begin human trials to cure sickle cell disease and beta-​thalassemia.2 Treatments for high cholesterol and a form of blindness are also on the verge of moving into humans as well, not to mention the plethora of projects to treat a range of genetic disorders that are currently being tested in animals and could one day benefit humans. In all cases, these diseases can be cured by reverting the mutated genetic code back to the “normal” sequence, reversions which were not possible with the traditional CRISPR scissor-​based approach.

    One-​time therapy

    CRISPR-​based technologies have an enormous upside. Today, patients suffering from hemophilia need multiple infusions per week. A CRISPR treatment, on the other hand, would ideally take place once, and the cells modified with CRISPR would persist for the rest of the patient’s life.

    This also means, however, that once the treatment has been started, it can no longer be discontinued. But would you choose a treatment where you can never stop taking the drug? This question arises with CRISPR-​based therapies.

    Safety concerns about unintended editing have mostly, but not entirely, been alleviated with next generation CRISPR molecular taxis. It must be stressed that the first generation treatments currently being clinically tested have underwent extensive studies to determine and limit detrimental effects. Nevertheless, the safety of CRISPR-​based systems must be kept in mind. It is important that the long-​term safety profiles of CRISPR technologies are established, and therefore I expect the first CRISPR-​treated patients will be monitored for life.

    A cure for previously incurable diseases

    Given all the safety considerations, one must also consider the therapeutic alternatives. Take progeria for example, a genetic disease in which children rapidly age and medication only exists to marginally extend lifespan. A next generation CRISPR technology currently under development has the potential to revolutionize progeria therapy: it doubled the lifespan in mouse models. For a fatal disease like progeria, for which there is no or inadequate therapy, many patients are likely to opt for a CRISPR treatment, even if there is some residual risk of potentially negative outcomes in the long term.

    The speed at which CRISPR technologies have advanced over the past decade has been tremendous. Regulatory agencies, which are required to assess the safety of these technologies, have sometimes failed to keep up with this pace. Urgently needed guidelines for the approval of the new technologies are not yet mature. This must change. There is a great need for action on the part of the regulatory authorities.

    The first decade of CRISPR has brought immense potential, rapid technological development, and the first patients treated. As we look to the next 10 years, both first and next generation CRISPR systems are poised to deliver on its potential and provide life-​long cures to patients of both rare and more common genetic disorders.

    See the full article here .

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

    Please help promote STEM in your local schools.

    Stem Education Coalition

    ETH Zurich campus

    The Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH) is a public research university in the city of Zürich, Switzerland. Founded by the Swiss Federal Government in 1854 with the stated mission to educate engineers and scientists, the school focuses exclusively on science, technology, engineering and mathematics. Like its sister institution The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne](CH) , it is part of The Swiss Federal Institutes of Technology Domain (ETH Domain)) , part of the The Swiss Federal Department of Economic Affairs, Education and Research [EAER][Eidgenössisches Departement für Wirtschaft, Bildung und Forschung] [Département fédéral de l’économie, de la formation et de la recherche] (CH).

    The university is an attractive destination for international students thanks to low tuition fees of 809 CHF per semester, PhD and graduate salaries that are amongst the world’s highest, and a world-class reputation in academia and industry. There are currently 22,200 students from over 120 countries, of which 4,180 are pursuing doctoral degrees. In the 2021 edition of the QS World University Rankings ETH Zürich is ranked 6th in the world and 8th by the Times Higher Education World Rankings 2020. In the 2020 QS World University Rankings by subject it is ranked 4th in the world for engineering and technology (2nd in Europe) and 1st for earth & marine science.

    As of November 2019, 21 Nobel laureates, 2 Fields Medalists, 2 Pritzker Prize winners, and 1 Turing Award winner have been affiliated with the Institute, including Albert Einstein. Other notable alumni include John von Neumann and Santiago Calatrava. It is a founding member of the IDEA League and the International Alliance of Research Universities (IARU) and a member of the CESAER network.

    ETH Zürich was founded on 7 February 1854 by the Swiss Confederation and began giving its first lectures on 16 October 1855 as a polytechnic institute (eidgenössische polytechnische schule) at various sites throughout the city of Zurich. It was initially composed of six faculties: architecture, civil engineering, mechanical engineering, chemistry, forestry, and an integrated department for the fields of mathematics, natural sciences, literature, and social and political sciences.

    It is locally still known as Polytechnikum, or simply as Poly, derived from the original name eidgenössische polytechnische schule, which translates to “federal polytechnic school”.

    ETH Zürich is a federal institute (i.e., under direct administration by the Swiss government), whereas The University of Zürich [Universität Zürich ] (CH) is a cantonal institution. The decision for a new federal university was heavily disputed at the time; the liberals pressed for a “federal university”, while the conservative forces wanted all universities to remain under cantonal control, worried that the liberals would gain more political power than they already had. In the beginning, both universities were co-located in the buildings of the University of Zürich.

    From 1905 to 1908, under the presidency of Jérôme Franel, the course program of ETH Zürich was restructured to that of a real university and ETH Zürich was granted the right to award doctorates. In 1909 the first doctorates were awarded. In 1911, it was given its current name, Eidgenössische Technische Hochschule. In 1924, another reorganization structured the university in 12 departments. However, it now has 16 departments.

    ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École polytechnique fédérale de Lausanne](CH), and four associated research institutes form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.

    Reputation and ranking

    ETH Zürich is ranked among the top universities in the world. Typically, popular rankings place the institution as the best university in continental Europe and ETH Zürich is consistently ranked among the top 1-5 universities in Europe, and among the top 3-10 best universities of the world.

    Historically, ETH Zürich has achieved its reputation particularly in the fields of chemistry, mathematics and physics. There are 32 Nobel laureates who are associated with ETH Zürich, the most recent of whom is Richard F. Heck, awarded the Nobel Prize in chemistry in 2010. Albert Einstein is perhaps its most famous alumnus.

    In 2018, the QS World University Rankings placed ETH Zürich at 7th overall in the world. In 2015, ETH Zürich was ranked 5th in the world in Engineering, Science and Technology, just behind the Massachusetts Institute of Technology, Stanford University and University of Cambridge (UK). In 2015, ETH Zürich also ranked 6th in the world in Natural Sciences, and in 2016 ranked 1st in the world for Earth & Marine Sciences for the second consecutive year.

    In 2016, Times Higher Education World University Rankings ranked ETH Zürich 9th overall in the world and 8th in the world in the field of Engineering & Technology, just behind the Massachusetts Institute of Technology, Stanford University, California Institute of Technology, Princeton University, University of Cambridge(UK), Imperial College London(UK) and University of Oxford(UK) .

    In a comparison of Swiss universities by swissUP Ranking and in rankings published by CHE comparing the universities of German-speaking countries, ETH Zürich traditionally is ranked first in natural sciences, computer science and engineering sciences.

    In the survey CHE Excellence Ranking on the quality of Western European graduate school programs in the fields of biology, chemistry, physics and mathematics, ETH Zürich was assessed as one of the three institutions to have excellent programs in all the considered fields, the other two being Imperial College London (UK) and the University of Cambridge (UK), respectively.

     
  • richardmitnick 8:04 am on July 5, 2022 Permalink | Reply
    Tags: "CRISPR 10 Years On:: Learning to Rewrite the Code of Life", "CRISPR": Clustered Regularly Interspaced Short Palindromic Repeats., , , , DNA, , Feng Zhang, , ,   

    From “The New York Times” : “CRISPR 10 Years On:: Learning to Rewrite the Code of Life” 

    From “The New York Times”

    June 30, 2022
    Carl Zimmer

    1
    The gene-editing technology has led to innovations in medicine, evolution and agriculture — and raised profound ethical questions about altering human DNA.

    Ten years ago this week, Jennifer Doudna and her colleagues published the results of a test-tube experiment on bacterial genes. When the study came out in the journal Science on June 28, 2012, it did not make headline news. In fact, over the next few weeks, it did not make any news at all.

    Looking back, Dr. Doudna wondered if the oversight had something to do with the wonky title she and her colleagues had chosen for the study: “A Programmable Dual RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity.”

    “I suppose if I were writing the paper today, I would have chosen a different title,” Dr. Doudna, a biochemist at the University of California-Berkeley, said in an interview.

    Far from an esoteric finding, the discovery pointed to a new method for editing DNA, one that might even make it possible to change human genes.

    “I remember thinking very clearly, when we publish this paper, it’s like firing the starting gun at a race,” she said.

    In just a decade, CRISPR has become one of the most celebrated inventions in modern biology. It is swiftly changing how medical researchers study diseases: Cancer biologists are using the method to discover hidden vulnerabilities of tumor cells. Doctors are using CRISPR to edit genes that cause hereditary diseases.

    Editing the genome with CRISPR

    “The era of human gene editing isn’t coming,” said David Liu, a biologist at Harvard University. “It’s here.”

    But CRISPR’s influence extends far beyond medicine. Evolutionary biologists are using the technology to study Neanderthal brains and to investigate how our ape ancestors lost their tails. Plant biologists have edited seeds to produce crops with new vitamins or with the ability to withstand diseases. Some of them may reach supermarket shelves in the next few years.

    CRISPR has had such a quick impact that Dr. Doudna and her collaborator, Emmanuelle Charpentier of the Max Planck Unit for the Science of Pathogens in Berlin, won the 2020 Nobel Prize for chemistry. The award committee hailed their 2012 study as “an epoch-making experiment.”

    3
    Jennifer Doudna shared the 2020 Nobel Prize for chemistry for her work on CRISPR. Credit: Anastasiia Sapon for The New York Times.

    Emmanuelle Charpentier via Relaxnews4
    Emmanuelle Charpentier, a French microbiologist with the Max Planck Unit for the Science of Pathogens in Berlin, who shared the Nobel Prize for Chemistry in 2020 with Dr. Doudna. Credit: Karsten Moran for The New York Times.

    Dr. Doudna recognized early on that CRISPR would pose a number of thorny ethical questions, and after a decade of its development, those questions are more urgent than ever.

    Will the coming wave of CRISPR-altered crops feed the world and help poor farmers or only enrich agribusiness giants that invest in the technology? Will CRISPR-based medicine improve health for vulnerable people across the world, or come with a million-dollar price tag?

    The most profound ethical question about CRISPR is how future generations might use the technology to alter human embryos. This notion was simply a thought experiment until 2018, when He Jiankui, a biophysicist in China, edited a gene in human embryos to confer resistance to H.I.V. Three of the modified embryos were implanted in women in the Chinese city of Shenzhen.

    In 2019, a court sentenced Dr. He to prison for “illegal medical practices.” MIT Technology Review reported in April that he had recently been released. Little is known about the health of the three children, who are now toddlers.

    Scientists don’t know of anyone else who has followed Dr. He’s example — yet. But as CRISPR continues to improve, editing human embryos may eventually become a safe and effective treatment for a variety of diseases.

    Will it then become acceptable, or even routine, to repair disease-causing genes in an embryo in the lab? What if parents wanted to insert traits that they found more desirable — like those related to height, eye color or intelligence?

    Françoise Baylis, a bioethicist at Dalhousie University in Nova Scotia, worries that the public is still not ready to grapple with such questions.

    “I’m skeptical about the depth of understanding about what’s at issue there,” she said. “There’s a difference between making people better and making better people.”

    Making the cut

    Dr. Doudna and Dr. Charpentier did not invent their gene-editing method from scratch. They borrowed their molecular tools from bacteria.

    In the 1980s, microbiologists discovered puzzling stretches of DNA in bacteria, later called Clustered Regularly Interspaced Short Palindromic Repeats. Further research revealed that bacteria used these CRISPR sequences as weapons against invading viruses.

    The bacteria turned these sequences into genetic material, called RNA, that could stick precisely to a short stretch of an invading virus’s genes. These RNA molecules carry proteins with them that act like molecular scissors, slicing the viral genes and halting the infection.

    As Dr. Doudna and Dr. Charpentier investigated CRISPR, they realized that the system might allow them to cut a sequence of DNA of their own choosing. All they needed to do was make a matching piece of RNA.

    To test this revolutionary idea, they created a batch of identical pieces of DNA. They then crafted another batch of RNA molecules, programming all of them to home in on the same spot on the DNA. Finally, they mixed the DNA, the RNA and molecular scissors together in test tubes. They discovered that many of the DNA molecules had been cut at precisely the right spot.

    For months Dr. Doudna oversaw a series of round-the-clock experiments to see if CRISPR might work not only in a test tube, but also in living cells. She pushed her team hard, suspecting that many other scientists were also on the chase. That hunch soon proved correct.

    In January 2013, five teams of scientists published studies in which they successfully used CRISPR in living animal or human cells. Dr. Doudna did not win that race; the first two published papers came from two labs in Cambridge, Mass. — one at the Broad Institute of M.I.T. and Harvard, and the other at Harvard.

    “Did you CRISPR that?”

    Lukas Dow, a cancer biologist at Weill Cornell Medicine, vividly remembers learning about CRISPR’s potential. “Reading the papers, it looked amazing,” he recalled.

    Dr. Dow and his colleagues soon found that the method reliably snipped out pieces of DNA in human cancer cells.

    “It became a verb to drop,” Dr. Dow said. “A lot of people would say, ‘Did you CRISPR that?’”

    Cancer biologists began systematically altering every gene in cancer cells to see which ones mattered to the disease. Researchers at KSQ Therapeutics, also in Cambridge, used CRISPR to discover a gene that is essential for the growth of certain tumors, for example, and last year, they began a clinical trial of a drug that blocks the gene.

    Caribou Biosciences, co-founded by Dr. Doudna, and CRISPR Therapeutics, co-founded by Dr. Charpentier, are both running clinical trials for CRISPR treatments that fight cancer in another way: by editing immune cells to more aggressively attack tumors.

    Those companies and several others are also using CRISPR to try to reverse hereditary diseases. On June 12, researchers from CRISPR Therapeutics and Vertex, a Boston-based biotech firm, presented at a scientific meeting new results from their clinical trial involving 75 volunteers who had sickle-cell anemia or beta thalassemia. These diseases impair hemoglobin, a protein in red blood cells that carries oxygen.

    The researchers took advantage of the fact that humans have more than one hemoglobin gene. One copy, called fetal hemoglobin, is typically active only in fetuses, shutting down within a few months after birth.

    The researchers extracted immature blood cells from the bone marrow of the volunteers. They then used CRISPR to snip out the switch that would typically turn off the fetal hemoglobin gene. When the edited cells were returned to patients, they could develop into red blood cells rife with hemoglobin.

    Speaking at a hematology conference, the researchers reported that out of 44 treated patients with beta thalassemia, 42 no longer needed regular blood transfusions. None of the 31 sickle cell patients experienced painful drops in oxygen that would have normally sent them to the hospital.

    CRISPR Therapeutics and Vertex expect to ask government regulators by the end of year to approve the treatment.

    Other companies are injecting CRISPR molecules directly into the body. Intellia Therapeutics, based in Cambridge and also co-founded by Dr. Doudna, has teamed up with Regeneron, based in Westchester County, N.Y., to begin a clinical trial to treat transthyretin amyloidosis, a rare disease in which a damaged liver protein becomes lethal as it builds up in the blood.

    4
    Equipment in the lab of Feng Zhang, a leading CRISPR researcher with the Broad Institute in Cambridge, Mass. Credit: Tony Luong for The New York Times.

    Doctors injected CRISPR molecules into the volunteers’ livers to shut down the defective gene. Speaking at a scientific conference last Friday, Intellia researchers reported that a single dose of the treatment produced a significant drop in the protein level in volunteers’ blood for as long as a year thus far.

    The same technology that allows medical researchers to tinker with human cells is letting agricultural scientists alter crop genes. When the first wave of CRISPR studies came out, Catherine Feuillet, an expert on wheat, who was then at the French National Institute for Agricultural Research, immediately saw its potential for her own work.

    “I said, ‘Oh my God, we have a tool,’” she said. “We can put breeding on steroids.”

    At Inari Agriculture, a company in Cambridge, Dr. Feuillet is overseeing efforts to use CRISPR to make breeds of soybeans and other crops that use less water and fertilizer. Outside of the United States, British researchers have used CRISPR to breed a tomato that can produce vitamin D.

    Kevin Pixley, a plant scientist at the International Maize and Wheat Improvement Center in Mexico City, said that CRISPR is important to plant breeding not only because it’s powerful, but because it’s relatively cheap. Even small labs can create disease-resistant cassavas or drought-resistant bananas, which could benefit poor nations but would not interest companies looking for hefty financial returns.

    Because of CRISPR’s use for so many different industries, its patent has been the subject of a long-running dispute. Groups led by the Broad Institute and the University of California both filed patents for the original version of gene editing based on CRISPR-Cas9 in living cells. The Broad Institute won a patent in 2014, and the University of California responded with a court challenge.

    In February of this year, the U.S. Patent Trial and Appeal Board issued what is most likely the final word on this dispute. They ruled in favor of the Broad Institute.

    Jacob Sherkow, an expert on biotech patents at the University of Illinois College of Law, predicted that companies that have licensed the CRISPR technology from the University of California will need to honor the Broad Institute patent.

    “The big-ticket CRISPR companies, the ones that are farthest along in clinical trials, are almost certainly going to need to write the Broad Institute a really big check,” he said.

    5
    Dr. Zhang of the Broad Institute, which recently won a major patent dispute over Crispr technology.Credit: Tony Luong for The New York Times.

    Prime CRISPR

    The original CRISPR system, known as CRISPR-Cas9, leaves plenty of room for improvement. The molecules are good at snipping out DNA, but they’re not as good at inserting new pieces in their place. Sometimes CRISPR-Cas9 misses its target, cutting DNA in the wrong place. And even when the molecules do their jobs correctly, cells can make mistakes as they repair the loose ends of DNA left behind.

    A number of scientists have invented new versions of CRISPR that overcome some of these shortcomings. At Harvard, for example, Dr. Liu and his colleagues have used CRISPR to make a nick in one of DNA’s two strands, rather than breaking them entirely. This process, known as base editing, lets them precisely change a single genetic letter of DNA with much less risk of genetic damage.

    Dr. Liu has co-founded a company called Beam Therapeutics to create base-editing drugs. Later this year, the company will test its first drug on people with sickle cell anemia.

    Dr. Liu and his colleagues have also attached CRISPR molecules to a protein that viruses use to insert their genes into their host’s DNA. This new method, called prime editing, could enable CRISPR to alter longer stretches of genetic material.

    “Prime editors are kind of like DNA word processors,” Dr. Liu said. “They actually perform a search and replace function on DNA.”

    Rodolphe Barrangou, a CRISPR expert at North Carolina State University and a founder of Intellia Therapeutics, predicted that prime editing would eventually become a part of the standard CRISPR toolbox. But for now, he said, the technique was still too complex to become widely used. “It’s not quite ready for prime time, pun intended,” he said.

    Gene-edited babies

    6
    Dr. He claimed to have created the first genetically edited twin babies at the University of Hong Kong in 2018. Credit: Alex Hofford/EPA, via Shutterstock.

    Advances like prime editing didn’t yet exist in 2018, when Dr. He set out to edit human embryos in Shenzen. He used the standard CRISPR-Cas9 system that Dr. Doudna and others had developed years before.

    Dr. He hoped to endow babies with resistance to H.I.V. by snipping a piece of a gene called CCR5 from the DNA of embryos. People who naturally carry the same mutation rarely get infected by H.I.V.

    In November 2018, Dr. He announced that a pair of twin girls had been born with his gene edits. The announcement took many scientists like Dr. Doudna by surprise, and they roundly condemned him for putting the health of the babies in jeopardy with untested procedures.

    Dr. Baylis of Dalhousie University criticized Dr. He for the way he reportedly presented the procedure to the parents, downplaying the radical experiment they were about to undertake. “You could not get an informed consent, unless you were saying, ‘This is pie in the sky. Nobody’s ever done it,’” she said.

    In the nearly four years since Dr. He’s announcement, scientists have continued to use CRISPR on human embryos. But they have studied embryos only when they’re tiny clumps of cells to find clues about the earliest stages of development. These studies could potentially lead to new treatments for infertility.

    Bieke Bekaert, a graduate student in reproductive biology at Ghent University in Belgium, said that CRISPR remains challenging to use in human embryos. Breaking DNA in these cells can lead to drastic rearrangements in the chromosomes. “It’s more difficult than we thought,” said Ms. Bekaert, the lead author of a recent review of the subject. “We don’t really know what is happening.”

    Still, Ms. Bekaert held out hope that prime editing and other improvements on CRISPR could allow scientists to make reliably precise changes to human embryos. “Five years is way too early, but I think in my lifetime it may happen,” she said.

    See the full article here .

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

    Please help promote STEM in your local schools.

    Stem Education Coalition

     
  • richardmitnick 12:28 pm on July 3, 2022 Permalink | Reply
    Tags: "When autism spectrum disorder occurs with intellectual disability a convergent mechanism for two top-ranking risk genes may be the cause", A significant proportion — approximately 31% — of people with ASD also exhibit ID., , , , DNA, , Microglia are very sensitive to pathological changes in the central nervous system and are the main form of active immune defense to maintain brain health., Preclinical study reveals that immune cells in the brain could be possible new drug targets for ASD and intellectual disability., The paper focuses on ADNP and POGZ-the two top-ranked risk factor genes for ASD/ID., The researchers are hopeful that future research will determine whether chronic neuroinflammation in which targeting microglia or inflammatory signaling pathways could prove to be a useful treatment., , two top-ranked genetic risk factors for autism spectrum disorder/intellectual disability (ASD/ID) lead to these neurodevelopmental disorders.   

    From The University at Buffalo-SUNY: “When autism spectrum disorder occurs with intellectual disability a convergent mechanism for two top-ranking risk genes may be the cause” 

    SUNY Buffalo

    From The University at Buffalo-SUNY

    June 30, 2022
    Ellen Goldbaum

    1
    “When designing clinical trials to evaluate treatment effectiveness, I think our research underscores the importance of considering the genetic factors involved in an individual’s ASD/ID,” said Conrow-Graham. The paper published in Brain is the culmination of her PhD work in the Jacobs School of Medicine and Biomedical Sciences. (Photo: Sandra Kicman)

    Preclinical study reveals that immune cells in the brain could be possible new drug targets for ASD and intellectual disability.

    University at Buffalo scientists have discovered a convergent mechanism that may be responsible for how two top-ranked genetic risk factors for autism spectrum disorder/intellectual disability (ASD/ID) lead to these neurodevelopmental disorders.

    While ASD is distinct from ID, a significant proportion — approximately 31% — of people with ASD also exhibit ID. Neither condition is well-understood at the molecular level.

    “Given the vast number of genes known to be involved in ASD/ID and the many potential mechanisms contributing to the disorders, it is exciting to find a shared process between two different genes at the molecular level that could be underlying the behavioral changes,” said Megan Conrow-Graham, first author and an MD/PhD candidate in the Jacobs School of Medicine and Biomedical Sciences at UB.

    Published today in the journal Brain, the paper focuses on ADNP and POGZ, the two top-ranked risk factor genes for ASD/ID. The research demonstrates that mutations in these genes result in abnormal activation and overexpression of immune response genes and genes for a type of immune cell in the brain called microglia.

    “Our finding opens the possibility of targeting microglia and immune genes for treating ASD/ID, but much remains to be studied, given the heterogeneity and complexity of these brain disorders,” said Zhen Yan, PhD, senior author and SUNY Distinguished Professor in the Department of Physiology and Biophysics in the Jacobs School.

    The UB scientists found that mutations in the two genes studied activate microglia and cause immune genes in the brain to be overexpressed. The hypothesized result is the abnormal function of synapses in the brain, a characteristic of ASD/ID.

    The research involved studies on postmortem brain tissue from humans with ASD/ID, as well as studies on mice in which ADNP and POGZ were silenced through viral delivery of small interference RNA. These mice exhibited impaired cognitive task performance, such as spatial memory, object recognition memory and long-term memory.

    Weakening a repressive function

    “Under normal conditions, cells in the central nervous system should not express large quantities of genes that activate the immune system,” said Conrow-Graham. “ADNP and POGZ both work to repress these genes so that inflammatory pathways are not continuously activated, which could damage surrounding cells. When that repression is weakened, these immune and inflammatory genes are then able to be expressed in large quantities.”

    The upregulated genes in the mouse prefrontal cortex caused by the deficiencies in ADNP or POGZ activated the pro-inflammatory response.

    “This is consistent with what we see in upregulated genes in the prefrontal cortex of humans with ASD/ID,” said Conrow-Graham. The prefrontal cortex is the part of the brain responsible for executive function, such as cognition and emotional control.

    The mutated genes also activate the glial cells in the brain called microglia, which serve as support cells for neurons and have an immune function in the brain; they comprise 10-15% of all brain cells.

    Sensitive microglia

    “Microglia are very sensitive to pathological changes in the central nervous system and are the main form of active immune defense to maintain brain health,” explained Yan. “Aberrant activation of microglia, which we demonstrate occurs as a result of deficiency in ADNP or POGZ, could lead to the damage and loss of synapses and neurons.”

    The researchers are hopeful that future research will determine whether chronic neuroinflammation could be directly contributing to at least some cases of ASD/ID, in which targeting microglia or inflammatory signaling pathways could prove to be a useful treatment.

    The researchers pointed out that the clinical presentation of both ASD and ID is incredibly varied. Significant variation also likely is present in the kinds of mechanisms responsible for the symptoms of ASD and/or ID.

    “We found that changes in two risk genes lead to a convergent mechanism, likely involving immune activation,” said Conrow-Graham. “However, this probably isn’t the case for all individuals with ASD/ID. When designing clinical trials to evaluate treatment effectiveness, I think our research underscores the importance of considering the genetic factors involved in an individual’s ASD/ID.”

    The research is the culmination of Conrow-Graham’s PhD work; she has now returned to complete the last two years of the MD degree in the Jacobs School. She described her experience pursuing both an MD and a PhD as extremely complementary.

    The immune system has a role

    “My training at each level was super helpful to supplement the other,” she said. “When I began my PhD, I had completed two years of MD training, so I was familiar with the basics of physiology, anatomy and pathology. Because of this, I was able to bring a broader perspective to my neuroscience research, identifying how the immune system might be playing a role. Prior to this, our lab had not really investigated immunology-related pathways, so having that background insight was really beneficial.”

    She added that she learned so much from all of her colleagues in Yan’s lab, including faculty members, lab technicians and other students. “I learned so many technical skills that I had never used before joining the lab, thanks to the dedication of lab co-workers for my training,” she said.

    Her experience at the lab bench working on the basic science underlying neuropsychiatric disorders will definitely influence her work as a clinician.

    “I plan to pursue a career as a child and adolescent psychiatrist, so I may be able to work directly with this patient population,” she said. “We’re learning now that better care may be able to be provided by taking a personalized medicine approach, taking into account genetics, psychosocial factors and others. Being able to take a very deep dive into the field of psychiatric genetics was a privilege that I hope will help me to provide the best care for patients.”

    The research was funded by the Nancy Lurie Marks Family Foundation and by a National Institutes of Health Ruth L. Kirschstein Individual Predoctoral NRSA for MD/PhD F30 fellowship for Conrow-Graham.

    In addition to Conrow-Graham and Yan, co-authors are Jamal B. Williams, PhD, former graduate student; Jennifer Martin, PhD, former postdoctoral fellow; Ping Zhong, PhD, senior research scientist; Qing Cao, PhD, postdoctoral fellow; and Benjamin Rein, PhD, former graduate student.

    All are current or former members of Yan’s lab.

    See the full article here .

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

    Please help promote STEM in your local schools.

    Stem Education Coalition

    SUNY Buffalo Campus

    The University at Buffalo-SUNY is a public research university with campuses in Buffalo and Amherst, New York, United States. The university was founded in 1846 as a private medical college and merged with the State University of New York system in 1962. It is one of four university centers in the system, in addition to The University at Albany-SUNY, The University at Binghampton-SUNY, and The University at Stony Brook-SUNY . As of fall 2020, the university enrolls 32,347 students in 13 colleges, making it the largest public university in the state of New York.

    Since its founding by a group which included future United States President Millard Fillmore, the university has evolved from a small medical school to a large research university. Today, in addition to the College of Arts and Sciences, the university houses the largest state-operated medical school, dental school, education school, business school, engineering school, and pharmacy school, and is also home to SUNY’s only law school. The University at Binghampton has the largest enrollment, largest endowment, and most research funding among the universities in the SUNY system. The university offers bachelor’s degrees in over 100 areas of study, as well as 205 master’s degrees, 84 doctoral degrees, and 10 professional degrees. The University at Buffalo and The University of Virginia are the only colleges founded by United States Presidents.

    The University at Buffalo is classified as an R1 University, meaning that it engages in a very high level of research activity. In 1989, UB was elected to The Association of American Universities, a selective group of major research universities in North America. University at Buffalo’s alumni and faculty have included five Nobel laureates, five Pulitzer Prize winners, one head of government, two astronauts, three billionaires, one Academy Award winner, one Emmy Award winner, and Fulbright Scholars.

    The University at Buffalo intercollegiate athletic teams are the Bulls. They compete in Division I of the NCAA, and are members of the Mid-American Conference.

    The University at Buffalo is organized into 13 academic schools and colleges.

    The School of Architecture and Planning is the only combined architecture and urban planning school in the State University of New York system, offers the only accredited professional master’s degree in architecture, and is one of two SUNY schools that offer an accredited professional master’s degree in urban planning. In addition, the Buffalo School of Architecture and Planning also awards the original undergraduate four year pre-professional degrees in architecture and environmental design in the SUNY system. Other degree programs offered by the Buffalo School of Architecture and Planning include a research-oriented Master of Science in architecture with specializations in historic preservation/urban design, inclusive design, and computing and media technologies; a PhD in urban and regional planning; and, an advanced graduate certificate in historic preservation.

    The College of Arts and Sciences was founded in 1915 and is the largest and most comprehensive academic unit at University at Buffalo with 29 degree-granting departments, 16 academic programs, and 23 centers and institutes across the humanities, arts, and sciences.

    The School of Dental Medicine was founded in 1892 and offers accredited programs in DDS, oral surgery, and other oral sciences.

    The Graduate School of Education was founded in 1931 and is one of the largest graduate schools at University at Buffalo. The school has four academic departments: counseling and educational psychology, educational leadership and policy, learning and instruction, and library and information science. In academic year 2008–2009, the Graduate School of Education awarded 472 master’s degrees and 52 doctoral degrees.

    The School of Engineering and Applied Sciences was founded in 1946 and offers undergraduate and graduate degrees in six departments. It is the largest public school of engineering in the state of New York. University at Buffalo is the only public school in New York State to offer a degree in Aerospace Engineering.

    The School of Law was founded in 1887 and is the only law school in the SUNY system. The school awarded 265 JD degrees in the 2009–2010 academic year.

    The School of Management was founded in 1923 and offers AACSB-accredited undergraduate, MBA, and doctoral degrees.

    The School of Medicine and Biomedical Sciences is the founding faculty of the University at Buffalo and began in 1846. It offers undergraduate and graduate degrees in the biomedical and biotechnical sciences as well as an MD program and residencies.

    The School of Nursing was founded in 1936 and offers bachelors, masters, and doctoral degrees in nursing practice and patient care.

    The School of Pharmacy and Pharmaceutical Sciences was founded in 1886, making it the second-oldest faculty at University at Buffalo and one of only two pharmacy schools in the SUNY system.

    The School of Public Health and Health Professions was founded in 2003 from the merger of the Department of Social and Preventive Medicine and the University at Buffalo School of Health Related Professions. The school offers a bachelor’s degree in exercise science as well as professional, master’s and PhD degrees.

    The School of Social Work offers graduate MSW and doctoral degrees in social work.

    The Roswell Park Graduate Division is an affiliated academic unit within the Graduate School of UB, in partnership with Roswell Park Comprehensive Cancer Center, an independent NCI-designated Comprehensive Cancer Center. The Roswell Park Graduate Division offers five PhD programs and two MS programs in basic and translational biomedical research related to cancer. Roswell Park Comprehensive Cancer Center was founded in 1898 by Dr. Roswell Park and was the world’s first cancer research institute.

    The University at Buffalo houses two New York State Centers of Excellence (out of the total 11): Center of Excellence in Bioinformatics and Life Sciences (CBLS) and Center of Excellence in Materials Informatics (CMI). Emphasis has been placed on developing a community of research scientists centered around an economic initiative to promote Buffalo and create the Center of Excellence for Bioinformatics and Life Sciences as well as other advanced biomedical and engineering disciplines.

    Total research expenditures for the fiscal year of 2017 were $401 million, ranking 59th nationally.

    SUNY’s administrative offices are in Albany, the state’s capital, with satellite offices in Manhattan and Washington, D.C.

    With 25,000 acres of land, SUNY’s largest campus is The SUNY College of Environmental Science and Forestry, which neighbors the State University of New York Upstate Medical University – the largest employer in the SUNY system with over 10,959 employees. While the SUNY system doesn’t officially recognize a flagship university, the University at Buffalo and Stony Brook University are sometimes treated as unofficial flagships.

    The State University of New York was established in 1948 by Governor Thomas E. Dewey, through legislative implementation of recommendations made by the Temporary Commission on the Need for a State University (1946–1948). The commission was chaired by Owen D. Young, who was at the time Chairman of General Electric. The system was greatly expanded during the administration of Governor Nelson A. Rockefeller, who took a personal interest in design and construction of new SUNY facilities across the state.

    Apart from units of the unrelated City University of New York (CUNY), SUNY comprises all state-supported institutions of higher education.

     
  • richardmitnick 11:56 am on July 1, 2022 Permalink | Reply
    Tags: "The beauty and benefits of biodiversity", Adaptability lies at the very heart of speciation., , As well as working with living organisms the researchers also study the genetic material of specimens held in collections., , , , , DNA, , , , , One of the most beautiful aspects of biodiversity is how species co-​evolve and exist together., , Species diversity is only one aspect of biodiversity-the others being habitat diversity and genetic diversity., Species diversity makes ecosystems resilient., The beauty of the world’s coral reefs never fails to amaze., , Time is of the essence because biodiversity is under threat and declining rapidly., Unfertilized minimally cultivated meadows and dry grasslands are incredibly diverse which makes them not just beautiful but essential., Using the eDNA method it took the researchers less than two years to confirm the presence of more fish species and families than experts had managed to identify during 13 years of reef dives.   

    From The Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH): “The beauty and benefits of biodiversity” 

    From The Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH)

    01.07.2022
    Peter Rüegg

    1

    Biodiversity is beautiful, but it’s also vitally important. ETH researchers are getting to the heart of how species diversity and genetic diversity evolve – and why we must fight to preserve them.

    Spring is synonymous with bright yellow dandelions, lush green fields and cloudless blue skies, a captivating combination of colours that sends many people into raptures of delight. Yet biodiversity researchers such as Alex Widmer, Professor of Plant Ecological Genetics in the Department of Environmental Systems Science, take a rather different view: “I know too much about ecosystems to take any pleasure in something so monotonous,” he says. His notion of beauty tends more towards dry grasslands and natural meadows rich in different species. “A far cry,” he says, “from the picture-​postcard idyll.” He argues that such areas are beautiful in much less obvious ways. Unfertilized, minimally cultivated meadows and dry grasslands are incredibly diverse, he says, which makes them not just beautiful, but essential.

    “Species diversity makes ecosystems resilient,” says Widmer, “and at the core of that resilience is genetic diversity.” Without genetic diversity, he explains, species and organisms cannot adapt to existing and evolving environmental conditions. And it’s this adaptability that lies at the very heart of speciation.

    2
    Natural meadows exhibit high levels of diversity. (Photograph: Peter Rüegg)

    Loïc Pellissier, Professor of Ecosystems and Landscape Evolution in the Department of Environmental Systems Science, agrees that much of the beauty of biodiversity is hidden from view. One of the most beautiful aspects of biodiversity, he says, is how species co-​evolve and exist together. “All organisms have evolved to interact with each other, as anyone who works in species diversity will tell you. To me, ecosystems are like huge jigsaw puzzles, in which all the pieces fit together more or less perfectly.” His research focuses on how species diversity arises and evolves. Because this occurs over the course of millions of years, Pellissier relies on computer models to simulate geological processes and the evolutionary forces that lead to the formation of new species.

    Genetic diversity

    Pellissier also conducts numerous field projects to unlock the secrets of species diversity. He favours a new and increasingly popular method that enables ecologists to detect species and organisms from the DNA they leave behind in the environment – known for short as environmental DNA, or eDNA. Researchers simply collect water and soil samples and analyse them to see what genetic material they contain. They then match whatever DNA they find to the corresponding organisms, provided a reference is available for this. This method provides a relatively quick way to determine whether a species is present in an ecosystem or not – and it works for a wide variety of organisms. “eDNA gives us a new insight into an ecosystem’s diversity,” he says.

    Recently, Pellissier co-​authored a study on the diversity of reef fish worldwide. Researchers collected over 200 seawater samples from various tropical coral reefs and then “fished out” whatever fish DNA they could find. Using the eDNA method it took the researchers less than two years to confirm the presence of more fish species and families than experts had managed to identify during 13 years of reef dives.

    Yet species diversity is only one aspect of biodiversity, the others being habitat diversity and genetic diversity. “Of the three, genetic diversity is the one that has been most neglected,” says Widmer. “Studying and monitoring genetic diversity is much more difficult and time-​consuming than monitoring habitats or species numbers.” Hence the numerous inventories of Swiss plants, animals and habitats – from forests and wetlands to dry grasslands. “Yet there isn’t a single monitoring project in Switzerland that focuses on the genetic diversity of living things,” says Widmer, “This is despite the fact that genetic diversity is fundamental for species diversity and adaptability.”

    To fill this gap, Widmer has joined forces with the Swiss Federal Institute for Forest, Snow and Landscape Research WSL on a project that aims to add this crucial element to Switzerland’s existing biodiversity monitoring systems. With the support of the Swiss Federal Office for the Environment (FOEN), Widmer and his colleagues have already launched a pilot study of five different species, including two plant species, a butterfly and a toad. The fifth species in their study is the yellowhammer, a songbird commonly found in cultivated areas of Switzerland. The researchers have already sequenced the genomes of one hundred individual yellowhammers from right across the country.

    4
    The beauty of the world’s coral reefs never fails to amaze. Yet behind such splendour, there lies much more – namely, a diverse habitat for a host of marine life. (Photograph: Stocksy)

    As well as working with living organisms, the researchers also study the genetic material of specimens held in collections. “This tells us whether populations from over 100 years ago were as diverse as today’s, or whether some of that genetic diversity has been lost,” says Widmer. Research into biodiversity in Switzerland has already revealed a sharp decline in species diversity, he notes: “We’d like to find out whether the same applies to genetic diversity.” Once the pilot study is complete, Widmer’s goal is to set up a large-​scale monitoring project encompassing up to 50 species. These would be examined at regular intervals to detect changes in their genetic diversity. However, it is still unclear whether this complex and ambitious project will receive the necessary funding.

    Fragile and endangered beauty

    Time is of the essence because biodiversity is under threat and declining rapidly. It is only by firmly fitting together the many different pieces of the biodiversity puzzle that we can slow the extinction of individual species. Reduce this network by half, and species will die out a thousand times faster – and when external pressures such as climate change are factored in, species extinction will occur a thousand times faster again.

    “Biodiversity is essential to our lives,” says Widmer. “It impacts everything from our mental well-​being to whether we have food on the table.” Diverse ecosystems are much more stable and better geared for the future than monotonous, species-​poor habitats. Pellissier nods in agreement: “Biodiversity is like classical art in the sense that it can’t be replaced. If the earth loses its biological riches, it will lose its magic.”

    See the full article here .

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

    Please help promote STEM in your local schools.

    Stem Education Coalition

    ETH Zurich campus

    The Swiss Federal Institute of Technology in Zürich [ETH Zürich] [Eidgenössische Technische Hochschule Zürich] (CH) is a public research university in the city of Zürich, Switzerland. Founded by the Swiss Federal Government in 1854 with the stated mission to educate engineers and scientists, the school focuses exclusively on science, technology, engineering and mathematics. Like its sister institution The Swiss Federal Institute of Technology in Lausanne [EPFL-École Polytechnique Fédérale de Lausanne](CH) , it is part of The Swiss Federal Institutes of Technology Domain (ETH Domain)) , part of the The Swiss Federal Department of Economic Affairs, Education and Research [EAER][Eidgenössisches Departement für Wirtschaft, Bildung und Forschung] [Département fédéral de l’économie, de la formation et de la recherche] (CH).

    The university is an attractive destination for international students thanks to low tuition fees of 809 CHF per semester, PhD and graduate salaries that are amongst the world’s highest, and a world-class reputation in academia and industry. There are currently 22,200 students from over 120 countries, of which 4,180 are pursuing doctoral degrees. In the 2021 edition of the QS World University Rankings ETH Zürich is ranked 6th in the world and 8th by the Times Higher Education World Rankings 2020. In the 2020 QS World University Rankings by subject it is ranked 4th in the world for engineering and technology (2nd in Europe) and 1st for earth & marine science.

    As of November 2019, 21 Nobel laureates, 2 Fields Medalists, 2 Pritzker Prize winners, and 1 Turing Award winner have been affiliated with the Institute, including Albert Einstein. Other notable alumni include John von Neumann and Santiago Calatrava. It is a founding member of the IDEA League and the International Alliance of Research Universities (IARU) and a member of the CESAER network.

    ETH Zürich was founded on 7 February 1854 by the Swiss Confederation and began giving its first lectures on 16 October 1855 as a polytechnic institute (eidgenössische polytechnische schule) at various sites throughout the city of Zurich. It was initially composed of six faculties: architecture, civil engineering, mechanical engineering, chemistry, forestry, and an integrated department for the fields of mathematics, natural sciences, literature, and social and political sciences.

    It is locally still known as Polytechnikum, or simply as Poly, derived from the original name eidgenössische polytechnische schule, which translates to “federal polytechnic school”.

    ETH Zürich is a federal institute (i.e., under direct administration by the Swiss government), whereas The University of Zürich [Universität Zürich ] (CH) is a cantonal institution. The decision for a new federal university was heavily disputed at the time; the liberals pressed for a “federal university”, while the conservative forces wanted all universities to remain under cantonal control, worried that the liberals would gain more political power than they already had. In the beginning, both universities were co-located in the buildings of the University of Zürich.

    From 1905 to 1908, under the presidency of Jérôme Franel, the course program of ETH Zürich was restructured to that of a real university and ETH Zürich was granted the right to award doctorates. In 1909 the first doctorates were awarded. In 1911, it was given its current name, Eidgenössische Technische Hochschule. In 1924, another reorganization structured the university in 12 departments. However, it now has 16 departments.

    ETH Zürich, EPFL (Swiss Federal Institute of Technology in Lausanne) [École polytechnique fédérale de Lausanne](CH), and four associated research institutes form The Domain of the Swiss Federal Institutes of Technology (ETH Domain) [ETH-Bereich; Domaine des Écoles polytechniques fédérales] (CH) with the aim of collaborating on scientific projects.

    Reputation and ranking

    ETH Zürich is ranked among the top universities in the world. Typically, popular rankings place the institution as the best university in continental Europe and ETH Zürich is consistently ranked among the top 1-5 universities in Europe, and among the top 3-10 best universities of the world.

    Historically, ETH Zürich has achieved its reputation particularly in the fields of chemistry, mathematics and physics. There are 32 Nobel laureates who are associated with ETH Zürich, the most recent of whom is Richard F. Heck, awarded the Nobel Prize in chemistry in 2010. Albert Einstein is perhaps its most famous alumnus.

    In 2018, the QS World University Rankings placed ETH Zürich at 7th overall in the world. In 2015, ETH Zürich was ranked 5th in the world in Engineering, Science and Technology, just behind the Massachusetts Institute of Technology, Stanford University and University of Cambridge (UK). In 2015, ETH Zürich also ranked 6th in the world in Natural Sciences, and in 2016 ranked 1st in the world for Earth & Marine Sciences for the second consecutive year.

    In 2016, Times Higher Education World University Rankings ranked ETH Zürich 9th overall in the world and 8th in the world in the field of Engineering & Technology, just behind the Massachusetts Institute of Technology, Stanford University, California Institute of Technology, Princeton University, University of Cambridge(UK), Imperial College London(UK) and University of Oxford(UK) .

    In a comparison of Swiss universities by swissUP Ranking and in rankings published by CHE comparing the universities of German-speaking countries, ETH Zürich traditionally is ranked first in natural sciences, computer science and engineering sciences.

    In the survey CHE Excellence Ranking on the quality of Western European graduate school programs in the fields of biology, chemistry, physics and mathematics, ETH Zürich was assessed as one of the three institutions to have excellent programs in all the considered fields, the other two being Imperial College London (UK) and the University of Cambridge (UK), respectively.

     
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