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  • richardmitnick 1:51 pm on April 27, 2016 Permalink | Reply
    Tags: , MicroRNA’s Role in Memory, Scripps Institute, Sleep and Synapse Function   

    From Scripps: “TSRI, Harvard, Stanford and Brandeis Collaborate to Study MicroRNA’s Role in Memory, Sleep and Synapse Function” 

    Scripps
    Scripps Research Institute

    April 27, 2016

    A group including scientists from the Florida campus of The Scripps Research Institute (TSRI) has been awarded a grant from the National Institute of Neurological Disorders and Stroke of the National Institutes of Health to study the role of microRNAs in a range of physiological activities, including memory, sleep, synapse function and movement.

    Ron Davis, chair of TSRI’s Department of Neuroscience, will be a principal investigator of the new five-year study with David Van Vactor of Harvard University, Leslie Griffith of Brandeis University and Dennis Wall of Stanford University.

    “This new collaboration with some of the best scientists at some of the best universities in the world has the potential to bring us a wealth of new and potentially groundbreaking knowledge about microRNAs,” Davis said. “Because microRNAs are so critical for normal development and physiology, they are a potentially rich source of therapeutic targets. Our new collaboration will help us exploit that potential.”

    Scripps Florida will receive approximately $2 million for the project over the next five years.

    MicroRNAs, as their name suggests, are tiny bits of genetic material. Instead of being translated into proteins like many RNAs, microRNAs act to regulate gene expression—acting like a dimmer switch on a light.

    In humans there are almost 2,000 distinct microRNAs, which collectively regulate somewhere between 30 and 80 percent of human genes.

    Despite their ubiquity, their importance has become evident only in the last decade or so, and details are still emerging. Davis noted a host of critical questions remain: How complex is the microRNA regulatory landscape for neural circuits mediating essential behaviors? To what extent are microRNA mechanisms used in the brain? Do they regulate distinct sets of target genes in different cell types and/or developmental stages?

    The new collaborative study will use Drosophila, the common fruit fly, which is a widely recognized substitute for human memory studies, to help answer some of these questions.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 10:34 am on March 28, 2016 Permalink | Reply
    Tags: , Scripps Institute,   

    From Scripps: “Team Uses CRISPR to Hit Hibernating HIV” 

    Scripps
    Scripps Research Institute

    March 28, 2016
    Elie Diner

    HIV is especially difficult to eliminate because it can hibernate in infected patients, eluding current antiretroviral drug therapy.

    Researchers at The Scripps Research Institute (TSRI) have now developed a new method to switch on, or reactivate, hibernating viruses and force them out of hiding. The breakthrough uses the CRISPR/Cas9 system, a genetic engineering tool that can be easily programmed, to target HIV and advance a potential cure.

    “Cas9 has been transformative for biology and in using it we’ve found a more specific and potent way of activating HIV,” said Kevin Morris, associate professor at TSRI and the University of New South Wales.

    1
    “Cas9 has been transformative for biology and in using it we’ve found a more specific and potent way of activating HIV,” says Associate Professor Kevin Morris.

    Morris was a senior author on the study, published recently in Molecular Therapy, with Marc Weinberg, adjunct assistant professor of molecular and experimental medicine at TSRI and professor of molecular medicine and haematology at the University of the Witwatersrand in Johannesburg, South Africa.

    Draining the HIV Reservoir

    HIV infections are currently treated with a combination of antiretroviral therapies (cART) that inhibit different stages in the viral life cycle. Use of these drugs has led to a large reduction in the morbidity, mortality and transmission associated with having HIV.

    However, cART is unable to target hibernating, or latent, HIV. Latency occurs when the viral genome integrates into the genome of an infected cell and enters an inactive state. In this state, there is a reduction in a cellular process called transcription, which is important for making HIV RNA, and no viral genes are produced.

    Cells carrying integrated HIV genomes act as a “reservoir” that enables HIV to come out of latency at any time, begin transcription of the viral genome and produce active virus. Reactivation is poorly understood, but can force many patients to continue cART for the duration of their lives.

    Several latency-reversing agents (LRAs) have been investigated to drive HIV out of hibernation by activating transcription of the HIV genome, yet many have nonspecific and unpredictable effects on cells, leading to a disruption of normal cell division or toxicity and making them unfavorable as therapeutics.

    “We wanted to find a potential LRA that could be as effective as the current therapeutics, but more specific,” said Weinberg of the group’s effort. To do this, the team investigated the use of the “dead” Cas9 (dCas9) system, a variant of the popular CRISPR gene editing system. dCas9 can be programmed to activate transcription at almost any sequence by using small guide RNAs (sgRNAs) that match a given DNA sequences. In this case, the group directed dCas9 to a region of the HIV genome where transcription normally begins.

    dCas9 Marks HIV ‘Hotspot’

    Morris, Weinberg and colleagues designed and tested 23 sgRNAs and analyzed their ability with dCas9 to activate transcription in several cell culture models for latent HIV. They found that targeting a small 20-30 nucleotide window led to strong activation of transcription, about 20-fold better than any of the other sequences targeted.

    The group went on to compare their dCas9 system to several LRAs, some of which have been investigated clinically. By targeting dCas9 to the “hotspot” region the researchers identified, they found that they could activate HIV better than many other methods.

    In addition, the team found its dCas9 system could specifically activate HIV with few off-target effects.

    As with this and other Cas9 therapies, the process of moving this proof-of-concept treatment into the clinic is in its infancy. “The million-dollar question with any of these types of approaches is the cellular delivery, and there are a lot of options for the use of CRISPR that should be looked at when applying these technologies,” said Weinberg.

    In addition to Weinberg and Morris, authors of the study, Potent and Targeted Activation of Latent HIV-1 Using the CRISPR/dCas9 Activator Complex, were co-first authors Sheena M. Saayman and Daniel C. Lazar, and Jonathan R. Hart of TSRI; Tristan A. Scott of the University of the Witwatersrand; Mayumi Takahashi and John C. Burnett of the Beckman Research Institute at the City of Hope; and Vicente Planelles of the University of Utah School of Medicine.

    2
    Key authors of the new paper include (left to right) Marc Weinberg, Daniel Lazar and Sheena Saayman. (Photo by Cindy Brauer.)

    The research was supported by the Strategic Health Innovation Partnerships Unit of South African Medical Research Council with funds received from the South African Medical Research Council, the National Institutes of Health (grants P01 AI099783-01, R01 AI111139-01 and R01 DK104681-01) and the Australian Research Council.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 2:17 pm on March 25, 2016 Permalink | Reply
    Tags: , Scripps Institute,   

    From Scripps: ” New Findings in Humans Provide Encouraging Foundation for Upcoming AIDS Vaccine Clinical Trial” 

    Scripps
    Scripps Research Institute

    March 28, 2016

    Some people infected with HIV naturally produce antibodies that effectively neutralize many strains of the rapidly mutating virus, and scientists are working to develop a vaccine capable of inducing such “broadly neutralizing” antibodies that can prevent HIV infection.

    An emerging vaccine strategy involves immunizing people with a series of different engineered HIV proteins as immunogens to teach the immune system to produce broadly neutralizing antibodies against HIV. This strategy depends on the ability of the first immunogen to bind and activate special cells, known as , which have the potential to develop into broadly neutralizing antibody-producing B cells.

    A research team has now found that the right precursor (germline) cells for one kind of HIV broadly neutralizing antibody are present in most people, and has described the design of an HIV vaccine germline-targeting immunogen capable of binding those B cells. The findings by scientists from The Scripps Research Institute (TSRI), the International AIDS Vaccine Initiative (IAVI) and the La Jolla Institute for Allergy and Immunology were published in Science on March 25.

    “We found that almost everybody has these broadly neutralizing antibody precursors, and that a precisely engineered protein can bind to these cells that have potential to develop into HIV broadly neutralizing antibody-producing cells, even in the presence of competition from other immune cells,” said the study’s lead author, William Schief, TSRI professor and director, Vaccine Design of the IAVI Neutralizing Antibody Center at TSRI, in whose lab the engineered HIV vaccine protein was developed.

    The body’s immune system contains a large pool of different precursor B cells so it can respond to a wide variety of pathogens. But that also means that precursor B cells able to recognize a specific feature on a virus surface are exceedingly rare within the total pool of B cells.

    “The challenge for vaccine developers is to determine if an immunogen can present a particular viral surface in a way that distinct B cells can be activated, proliferate and be useful,” said study co-author Shane Crotty, professor at the La Jolla Institute. “Using a new technique, we were able to show—well in advance of clinical trials—that most humans actually have the right B cells that will bind to this vaccine candidate. It is remarkable that protein design can be so specific as to ‘find’ one in a million cells, demonstrating the feasibility of this new vaccine strategy.”

    The work offers encouraging insights for a planned Phase 1 clinical trial to test a nanoparticle version of the engineered HIV vaccine protein, the “eOD-GT8 60mer.” “The goal of the clinical study will be to test safety and the ability of this engineered protein to elicit the desired immune response in humans that would look like the start of broadly neutralizing antibody development,” Schief said. “Data from this new study was also important for designing the clinical trial, including the size and the methods of analysis.”

    In June, scientists from TSRI, IAVI and The Rockefeller University reported that the eOD-GT8 60mer produced antibody responses in mice that showed some of the traits necessary to recognize and inhibit HIV. If the eOD-GT8 60mer performs similarly in humans, additional boost immunogens are thought to be needed to ultimately induce broadly neutralizing antibodies that can block HIV.

    The new work also provides a method for researchers to assess whether other new vaccine proteins can bind their intended precursor B cells. This method is a valuable tool in the design of more targeted and effective vaccines against AIDS, providing the ability to vet germline-targeting immunogens before testing them in large, time-consuming and costly clinical trials.

    Looking at blood donated by healthy volunteers, the scientists found B cells that were capable of creating “VRC01-class” antibodies that recognized a critical surface patch, or epitope, of HIV. VRC01-class broadly neutralizing antibodies are a group of antibodies isolated from different individuals that appear to have developed in a very similar way, and it has been hypothesized that the starting VRC01-class B cells were very similar in the different people. The eOD-GT8 60mer is designed to engage these precursor B cells to initiate HIV broadly neutralizing antibody development.

    Other contributors to the paper, HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen, included Joseph Jardine, Daniel Kulp, Colin Havenar-Daughton, Anita Sarkar, Bryan Briney, Devin Sok, Fabian Sesterhenn, June Ereno-Orbea, Oleksandr Kalyuzhniy, Isaiah Deresa, Xiaozhen Hu, Skye Spencer, Meaghan Jones, Erik Georgeson, Jumiko Adachi, Michael Kubitz, Allan decamp, Jean-Philippe Julien, Ian Wilson and Dennis Burton. This work was supported by the International AIDS Vaccine Initiative Neutralizing Antibody Consortium and Center; the Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology and Harvard; the Bayer Science and Education Foundation; the Helen Hay Whitney Foundation; Howard Hughes Medical Institute; Bill & Melinda Gates Foundation; and the National Institute of Allergy and Infectious Diseases (P01 AI094419, Center for HIV/AIDS Vaccine Immunology & Immunogen Discovery (CHAVI- ID) 1UM1AI100663, P01 AI82362 and R01 AI084817.)

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 10:43 am on March 18, 2016 Permalink | Reply
    Tags: , , Scripps Institute   

    From Scripps: “Scripps Florida Scientists Win $1.4 Million Grant to Develop New Ways to Block Breast Cancer” 

    Scripps
    Scripps Research Institute

    March 18, 2016
    Office of Communications
    Tel: 858-784-2666
    Fax: 858-784-8136
    press@scripps.edu

    Scientists from the Florida campus of The Scripps Research Institute (TSRI) have received a $1.4 million grant from the Department of Defense to develop a series of drug candidates that act against molecules closely linked with the growth of cancer cells.

    Donald G. Phinney, a TSRI professor and acting chairman of the Department of Molecular Therapeutics, is the principal investigator of the new three-year grant.

    “The focus of our research will be on breast cancer,” Phinney said. “We’re targeting a specific microRNA—microRNAs don’t produce proteins but can still regulate gene expression—because of its pivotal role in breast cancer. By blocking it, we think we can stop or, at the very least, impede tumor growth, with less toxicity than is often associated with chemotherapy.”

    Recent research has shown that virtually all cancer cells experience what is known as “hypoxic stress”—periods of low oxygen. But cancer cells can adapt by slowing their growth rate and metabolism, which increases the cells’ ability to survive. Adaptation to hypoxia is now seen as critical to tumor growth, metastasis and development of drug resistance.

    The microRNA that is the focus of the new study is induced by low oxygen and plays a vital role in breast cancer cells’ adaptation to that stressful environment.

    “Some preliminary studies have shown that inhibition of this microRNA increases the sensitivity of these incipient cancer cells to hypoxia-induced death and makes drug-resistant cancer cells more vulnerable to chemotherapy with low toxicity,” Phinney said. “Moreover, drugs that target microRNAs provide more durable and potent effects precisely because they attack entire pathways disrupted by cancer, as opposed to drugs that target a single protein, which are susceptible to drug resistance.”

    The approach taken in the new study is broad enough to identify and target a number of different microRNAs implicated in breast and other cancers. This work is being done in collaboration with TSRI Professor Matthew Disney, who has pioneered the development of RNA-targeting drug therapies.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 2:17 pm on March 15, 2016 Permalink | Reply
    Tags: , Kidney transplant rejection, , Scripps Institute   

    From Scripps: “TSRI Scientists Identify Molecular Markers of Kidney Transplant Rejection” 

    Scripps
    Scripps Research Institute

    March 15, 2016

    Findings Challenge Assumptions in the Field and Open the Door to Early Intervention

    Despite advances in organ transplant medicine in recent decades, about half of all kidney transplant patients still lose their organ to rejection within 10 years.

    Now a study led by scientists at The Scripps Research Institute (TSRI) shows that genome-wide molecular profiling of kidney biopsies may be a key to catching organ rejection before it’s too late. The research demonstrates that acute and chronic kidney rejection—currently believed to be separate diseases—are actually different parts of the arc of the same immune rejection process.

    “For our transplant population, this is a major new understanding of the molecular basis of immune rejection that challenges the field to reconsider its current paradigms and has multiple immediate and actionable therapy implications for patients,” said TSRI Professor Daniel Salomon, MD, director of the Laboratory for Functional Genomics at TSRI, medical program director of the Scripps Center for Organ Transplantation and leader of the multi-institution Transplant Genomics Collaborative Group (TGCG). “The insights here most likely apply to liver, heart and lung transplants, too.”

    The research was published online ahead of print on March 15, 2016, by the American Journal of Transplantation.

    Patients Haunted by Rejection

    Sometimes kidney rejection is quick to strike (acute and early)—the patient’s immune system attacks the “foreign” organ, and the kidney begins to fail within a year of transplant. Other cases of rejection move slowly (chronic and late), appearing years after the transplant and causing a progressive loss of kidney structure and function.

    Doctors treat acute rejection by administering more immunosuppressant drugs, which knock back the body’s immune response, helping the new kidney function normally. Because chronic rejection presents to clinicians so differently, most doctors see it as a different and untreatable “disease” and believe losing the organ is inevitable.

    “Part of this thinking about chronic rejection is reinforced by the fact that transplant physicians can’t diagnose it with current methods until there is too much tissue damage to treat or reverse the loss of the transplant,” said Salomon. “Moreover, because immunosuppressive drugs have toxicities, there is a constant pressure for doctors to reduce doses over time. Thus, the level of immunosuppression is also reduced until it finally becomes inadequate for some patients and they reject.”

    Patients who lose the organ to rejection must return to dialysis, which is more expensive than a kidney transplant, and face higher risks of complications, including death.

    Surprising Findings

    In the new study, Salomon and his colleagues investigated whether acute and chronic rejection are related. The researchers used a technique called gene expression profiling, which measures the activity of thousands of genes at once, to compare chronic rejection, acute rejection and healthy transplant patients.

    TSRI Staff Scientist Sunil Kurian, co-author of the new study, called genetic expression profiling a “genomic microscope,” that provides different, and often more definitive, information than the light microscopes usually used by pathologists to evaluate kidney tissues.

    In the new study, Brian Modena, the first author of the study and a physician-scientist supported in Salomon’s laboratory by a grant to Eric Topol, director of the Scripps Translational Science Institute, applied a new computational tool to gene expression analysis called Gene Co-Expression Networks (GCN) that revealed the actual molecular mechanisms involved in immune rejection in these different biopsies.

    In an analysis of 234 kidney transplant biopsies, the research team found that about 80 percent of genes expressed in acute rejection samples—including many genes related to inflammation and injury—were also expressed in chronic rejection samples.

    “It’s all the same disease—whether it’s one month post-transplant or five years post-transplant,” said Salomon. “Immune-mediated rejection is a single entity at the molecular level.”

    The researchers added that this entire spectrum of transplant rejection can potentially be treated with the same immunosuppressant therapies.

    “The new view that emerges from this research is that almost all transplant organ failure is due to inadequate immunosuppression, and with that understanding comes a potential for a major change in the practice of post-transplant drug therapy,” said Salomon.

    Other Early Warning Signs

    The researchers also identified a clue that rejection might be lurking: a kind of kidney damage and scarring called interstitial fibrosis and tubular atrophy (IFTA). Previous studies found that the presence of IFTA and inflammation—as seen under a light microscope—correlated with an increased risk of rejection, but IFTA on its own has been seen as evidence of a past injury, not active rejection, and is rarely treated.

    The new research suggests that IFTA is indeed a sign of active but “silent” rejection, as molecular profiling revealed similar genes are expressed in IFTA patients and acute rejection patients.

    “There was injury and inflammation there, just like in acute rejection patients—we just weren’t able to see it with the light microscope,” said Modena. “If you catch that early, you might potentially prevent chronic rejection. That would be a hugely positive benefit for our patients.”

    Genetic expression profiling also proved to be a good tool for detecting “subclinical” acute rejection, which is active in about 20 percent of transplant patients in their first year and is otherwise impossible to suspect or diagnose until progression to clinical rejection.

    Next Steps

    Given the results of the new study, Salomon said that an important development would be for physicians to take regular biopsies from transplant patients, called surveillance biopsies. (This is now standard of care for the Scripps Center for Organ Transplantation and is performed at 2, 6, 12 and 24 months post-transplantation in all eligible patients.) Molecular expression profiling of these biopsies could help doctors detect early signs of acute and chronic rejection.

    Salomon pointed out that such molecular profiling might even be performed via a blood test, preventing the need for multiple, invasive surveillance biopsies and allowing clinicians to measure the state of the immune response and the efficacy of immunosuppression at any time. He said such a blood test, described last year in the American Journal of Transplantation, is currently being validated in another National Institutes of Health-funded project as part of the Clinical Trials in Organ Transplantation (CTOT) consortium.

    The scientists also plan to investigate the genetic expression profiles of patients with diseases such as asthma and ulcerative colitis, in which the immune system is also active. “There is much in common between immune-based diseases and much to learn about what is shared and unique,” said Modena.

    In addition to Salomon, Kurian and Modena, authors of the study, “Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms that Correlate with Worse Long-term Outcomes,” were Lillian W. Gaber of The Methodist Hospital; Raymond Heilman of the TGCG and the Mayo Clinic; John J. Friedewald and Michael M. Abecassis of the Northwestern Comprehensive Transplant Center; Stuart Flechner of the TGCG and the Cleveland Clinic Foundation; Christopher L. Marsh of the TGCG and Scripps Health; Randall S. Sung of the TGCG and the University of Michigan, Ann Arbor; Hamid Shidban of the TGCG and St. Vincent Medical Center; Laurence Chan of the TCGC and the University of Colorado; and Jill Waalen, Andrew I. Su, Terri Gelbart, Tony S. Mondala, Steven R. Head and Suzanne Papp of TSRI.

    This research was supported by the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (grants U19 AI063603 and U01 AI084146-05) and the NIH Clinical and Translational Science Awards Program (grant CTSA KL2 TR001112).

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 6:32 pm on March 7, 2016 Permalink | Reply
    Tags: , , Scripps Institute   

    From Scripps: “Team Finds New Approach to Curbing Cancer Cell Growth” 

    Scripps
    Scripps Research Institute

    March 7, 2016

    Using a new approach, scientists at The Scripps Research Institute (TSRI) and collaborating institutions have discovered a novel drug candidate that could be used to treat certain types of breast cancer, lung cancer and melanoma.

    The new study focused on serine, one of the 20 amino acids (protein building blocks) found in nature. Many types of cancer require synthesis of serine to sustain rapid, constant and unregulated growth.

    To find a drug candidate that interfered with this pathway, the team screened a large library of compounds from a variety of sources, searching for molecules that inhibited a specific enzyme known as 3-phosphoglycerate dehydrogenase (PHGDH), which is responsible for the first committed step in serine biosynthesis.

    “In addition to discovering an inhibitor that targets cancer metabolism, we also now have a tool to help answer interesting questions about serine metabolism,” said Luke L. Lairson, assistant professor of chemistry at TSRI and principal investigator of cell biology at the California Institute for Biomedical Research (CALIBR).

    Lairson was senior author of the study, published recently in the Proceedings of the National Academy of Sciences (PNAS), with Lewis Cantley of Weill Cornell Medical College and Costas Lyssiotis of the University of Michigan.

    Addicted to Serine

    Serine is necessary for nucleotide, protein and lipid biosynthesis in all cells. Cells use two main routes for acquiring serine: through import from the extracellular environment or through conversion of 3-phosphoglycerate (a glycolytic intermediate) by PHGDH.

    “Since the late 1950s, it has been known that cancer cells use the process of aerobic glycolysis to generate metabolites needed for proliferative growth,” said Lairson.

    This process can lead to an overproduction of serine. The genetic basis for this abundance had remained mysterious until recently, when it was demonstrated that some cancers acquire mutations that increased the expression of PHGDH; reducing PHGDH in these “serine-addicted” cancer cells also inhibited their growth.

    The labs of Lewis C. Cantley at Weill Cornell Medical College (in work published in Nature Genetics) and David Sabatini at the Whitehead Institute (in work published in Nature) suggested PHGDH as a potential drug target for cancer types that overexpress the enzyme.

    Lairson and colleagues hypothesized that a small molecule drug candidate that inhibited PHGDH could interfere with cancer metabolism and point the way to the development of an effective cancer therapeutic. Importantly, this drug candidate would be inactive against normal cells because they would be able to import enough serine to support ordinary growth.

    As Easy as 1-2-800,000

    Lairson, in collaboration with colleagues including Cantley, Lyssiotis, Edouard Mullarky of Weill Cornell and Harvard Medical School and Natasha Lucki of CALIBR, screened through a library of 800,000 small molecules using a high-throughput in vitro enzyme assay to detect inhibition of PHGDH. The group identified 408 candidates and further narrowed this list down based on cell-type specific anti-proliferative activity and by eliminating those inhibitors that broadly targeted other dehydrogenases.

    With the successful identification of seven candidate inhibitors, the team sought to determine if these molecules could inhibit PHGDH in the complex cellular environment. To do so, the team used a mass spectrometry-based assay (test) to measure newly synthesized serine in a cell in the presence of the drug candidates.

    One of the seven small molecules tested, named CBR-5884, was able to specifically inhibit serine synthesis by 30 percent, suggesting that the molecule specifically targeted PHGDH. The group went on to show that CBR-5884 was able to inhibit cell proliferation of breast cancer and melanoma cells lines that overexpress PHGDH.

    As expected, CBR-5884 did not inhibit cancer cells that did not overexpress PHGDH, as they can import serine; however, when incubated in media lacking serine, the presence of CBR-5884 decreased growth in these cells.

    The group anticipates much optimization work before this drug candidate can become an effective therapeutic. In pursuit of this goal, the researchers plan to take a medicinal chemistry approach to improve potency and metabolic stability.

    In addition to Lairson, Cantley, Lyssiotis, Mullarky and Lucki, authors of the study, “Identification of a small molecule inhibitor of 3-phosphoglycerate dehydrogenase to target serine biosynthesis in cancers” were Reza Beheshti Zavereh and Justin L. Anglin of CALIBR; Ana P. Gomes, Jenny C. Y. Wong, Pradeep K. Sigh, John Blenis, J. David Warren and Gina M. DeNicola of Weill Cornell; Brandon N. Nicolay of Harvard Medical School, Stefan Christen and Sarah-Maria Fendt of Belgium’s Katholieke Universiteit Leuven and Vlaams Instituut voor Biotechnologie Leuven; Hidenori Takahashi, at the time of the study of Beth Israel Deaconess Medical Center and Harvard Medical School; and John M. Asara of Beth Israel Deaconess Medical Center and Harvard Medical School.

    The research was supported by the National Institutes of Health (grants P01 CA117969 and P01 CA120964), the PanCAN-AACR Pathway to Leadership Award, the Dale F. Frey Award for Breakthrough Scientists from the Damon Runyon Cancer Research Foundation and the Conquer Cancer Now Award from the Concern Foundation.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 4:52 pm on March 3, 2016 Permalink | Reply
    Tags: , Scripps Institute,   

    From Scripps: “New TSRI Study Shows HIV Structure in Unprecedented Detail” 

    Scripps
    Scripps Research Institute

    March 3, 2016
    Office of Communications
    Tel: 858-784-2666
    Fax: 858-784-8136
    press@scripps.edu

    A new study from scientists at The Scripps Research Institute (TSRI) describes the high-resolution structure of the HIV protein responsible for recognition and infection of host cells.

    The study, published today in the journal Science, is the first to show this HIV protein, known as the envelope (Env) trimer, in its natural or “native” form. The findings also include a detailed map of a vulnerable site at the base of this protein, as well as the binding site of an antibody that can neutralize HIV.

    HIV trimer
    HIV trimer. No image credit.

    “This structure has been elusive because its fragility typically causes it to fall apart before it can be imaged,” said TSRI Associate Professor Andrew Ward, senior author of the study. “Now that we know what the native state looks like, the next step is to look at vaccine applications.”

    Studying HIV’s Defenses

    Imagine an airplane going in for a landing. Now imagine the airport runway is covered with heaps of barbed wire.

    This is the kind of challenge human antibodies face when they attempt to neutralize HIV.

    “The immune system can generate a response, but those responses can’t effectively hit the virus,” said Ward.

    Ideally, antibodies would be able to target HIV’s Env trimer—three loosely connected proteins that stick out of the virus’s membrane and enable the virus to fuse with and infect host cells. This “fusion machinery” is also a valuable target because its structure is highly conserved, meaning the same vulnerabilities exist on many strains of the virus, and antibodies against these sites could be “broadly neutralizing.” Unfortunately, a “shield” of sugar molecules, called glycans, blocks many antibodies from reaching this region.

    To develop a vaccine against HIV, researchers need a detailed map of these glycans to reveal the small holes in the shield where antibodies might penetrate and neutralize the underlying viral machinery.

    The HIV trimer is notoriously unstable, however, making it hard for scientists to capture a good image. Partly due to this limitation, previous studies at TSRI and other institutions had shown only truncated trimers or high-resolution models of mutation-stabilized trimers. No one had a clear view of the trimer and its glycan defenses in their native form.

    New Techniques Lead to Detailed Map

    In the new study, the researchers employed cryo-electron microscopy (EM)—a 3D imaging technique that enables resolution of atomic-level details. TSRI maintains a state-of-the-art cryo-EM suite that includes a powerful Titan Krios cryo-electron microscope and a new generation of digital camera, the Gatan K2 Summit.

    The researchers devised a strategy to extract and purify the fragile HIV Env trimer from its membrane environment and load it into the microscope for imaging. The process involved the use of an HIV broadly neutralizing antibody, PGT151, previously discovered in the lab of TSRI Professor Dennis Burton (also scientific director of the International AIDS Vaccine Initiative’s (IAVI) Neutralizing Antibody Center and the National Institutes of Health (NIH)-sponsored Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), both at TSRI).

    The resulting images included a more-complete trimer structure than ever seen before. Researchers could see the complete fusion machinery, complex glycans and a vaccine target called the membrane proximal external region (MPER). The structures also demonstrated that the trimer is malleable and can subtly alter its shape. This shape-shifting is both part of its fusion machinery and a way to dodge neutralizing antibody responses.

    The structure also includes a highly detailed picture of the PGT151 site of vulnerability, the most complex and extensive broadly neutralizing epitope (site that antibodies can recognize) yet described. In addition to targeting several glycans on the surface of Env, PGT151 binds to the fusion peptide—rendering the virus unable to infect host cells.

    In addition, the researchers used this more complete trimer to study an antibody that binds to MPER. In the past, 3D structures of this region had only been studied using trimer fragments.

    The findings give researchers a better idea of the antibody traits needed to negotiate the glycan shield. “That’s extremely important to know when you’re trying to develop a vaccine against HIV,” said Jeong Hyun Lee, a graduate student in the Ward lab and first author of the study.

    Ward said the newly solved structure is similar to the Env trimer-mimicking structures being developed for an HIV vaccine and confirms that vaccine strategies are on target. Researchers can now build on that work to develop superior vaccine candidates.

    In addition to Ward and Lee, the other author of the study, “Cryo-EM structure of a native, fully glycosylated, cleaved HIV-1 envelope trimer,” was Gabriel Ozorowski of TSRI.

    This work was supported by the National Institutes of Health (grant UM1 AI100663), the National Institutes of Health (NIH)-sponsored Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI, the International AIDS Vaccine Initiative’s (IAVI) Neutralizing Antibody Consortium through the Bill & Melinda Gates Foundation’s Collaboration for AIDS Vaccine Discovery (grants OPP1084519 and OPP1115782) and the California HIV/AIDS Research Program Dissertation Award. IAVI’s support for the study was made possible in part by the generous support of the American people through the United States Agency for International Development (USAID), which administers the U.S. foreign assistance program providing economic and humanitarian assistance in more than 120 countries worldwide

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 1:15 pm on February 22, 2016 Permalink | Reply
    Tags: , Autoimmune diseases, Scripps Institute   

    From Scripps: “TSRI Researchers Uncover Potential Target for Treating Autoimmune Disease” 

    Scripps
    Scripps Research Institute

    February 22, 2016
    Office of Communications
    Tel: 858-784-2666
    Fax: 858-784-8136
    press@scripps.edu

    Scientists from The Scripps Research Institute (TSRI) have identified a molecule that appears to be a cause of autoimmune diseases such as lupus. Elevated levels of the molecule allow self-reactive immune cells to escape into the blood stream and attack the body’s own tissues.

    “This is a good target for future therapies,” said TSRI Associate Professor Changchun Xiao, who was co-senior author of the study with TSRI Professor David Nemazee. “We now know that this is causative—it’s not just a side effect.”

    The research, published February 22, 2016, in the journal Nature Immunology, focused on the identification of a specific microRNA (miRNA)—a small non-coding RNA molecule playing a role in regulating gene expression—that affects the immune system.

    Alicia Gonzalez-Martin, research associate in the Xiao lab and first author of the new study, was excited by the discovery. “This is the first miRNA implicated in the regulation of B cell tolerance,” she said.

    Clues in Mouse Models

    Immune cells known as B cells develop in the bone marrow and acquire specific receptors in a random assembly process that helps the body prepare to fight different enemies, including a multitude of viruses and bacteria. Xiao compared the assembly process to handing soldiers different kinds of weapons—a rifle for one soldier, a bayonet for another.

    Normally, the body also has a system of B cell tolerance checkpoints in place to eliminate self-reactive B cells, which attack not only germs but also the body’s own tissues. This process, which relies on apoptosis (programmed cell death), seems to go awry in patients with autoimmune diseases. “For some reason, their self-reactive B cells have not been purged,” said Xiao.

    The new research began when Nemazee’s lab engineered a mouse model of immune tolerance, which rendered all B cells self-reactive. As a result, the cells continually eliminated themselves by natural self-tolerance processes, leading to an absence of B cells in the body. The researchers, however, noticed a strange phenomenon—as the mice got older, some self-reactive B cells escaped into the blood stream. The phenomenon reminded the researchers of cells seen in autoimmune diseases and suggested a way to search for genes whose dysregulation hindered tolerance and promoted such diseases.

    The scientists hypothesized that some of the more than 1,000 known miRNAs might be affecting the gene expression regulating the survival or destruction of self-reactive B cells. The challenge was to pinpoint the exact miRNA responsible.

    “This was a risky project because we weren’t sure if any miRNA at all would regulate B cell tolerance,” explained Gonzalez-Martin.

    Setting the Trap

    Finding the miRNA culprit meant setting a trap.

    The team first generated its own self-reactive B cells by prompting a virus to express select miRNAs in haematopoietic stem cells (stem cells producing blood cells and platelets). The researchers then seeded the bone marrow of the Nemazee lab’s mouse model with these cells.

    Eventually, some of these self-reactive B cells escaped into the spleens of the mice, where researchers caught and analyzed the miRNAs expressed.

    The researchers found elevated expression of a specific miRNA called miR-148a that was responsible for B cell escape. MiR-148a suppressed three genes that control apoptosis. Without apoptosis, self-reactive mutants were not purged.

    When the team prompted mouse models of lupus to overexpress miR-148a, the mice developed lupus faster than their counterparts with normal miR-148a expression. Interestingly, miR-148a is also overexpressed in many human lupus patients.

    “This brings us to a pathway that we might be able to regulate with a therapeutic,” Nemazee said.

    The researchers said the next step is to investigate miR-148a’s other functions in the body to see if inhibiting its actions would have any negative side effects.

    In addition to Xiao, Nemazee and Gonzalez-Martin, authors of the study “The microRNA miR-148a functions as a critical regulator of B cell tolerance and autoimmunity,” were Brian D. Adams and Jun Lu of Yale University; Maria Salvador-Bernaldez and Jesus M. Salvador of the National Biotechnology Center, Madrid, Spain; and Maoyi Lai and Jovan Shepherd of TSRI.

    The study was supported by the Pew Charitable Trusts, The Cancer Research Institute, Lupus Research Institute and National Institutes of Health (grants R01 AI089854, R01 AI59714 and RC4 AI092763).

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 12:36 pm on February 16, 2016 Permalink | Reply
    Tags: , Breast cancer, , Scripps Institute   

    From Scripps: “Stopping Breast Cancer in its Tracks” 

    Scripps
    Scripps Research Institute

    February 2016
    No writer credit found

    Targeted cancer therapies customized to act only on specific tumor cells allow doctors to stop tumor growth while causing little or no harm to normal cells. While many types of breast cancer can be treated this way, others still cannot.

    Now, scientists from Scripps Florida have identified a compound that may serve as a new approach for treating certain breast cancers.

    The study points to an enzyme called casein kinase 1δ (CK1δ), a critical regulator of growth, as a novel and highly vulnerable therapeutic target. Increased CK1δ expression is common to breast cancer, including the difficult-to-treat subtype called triple negative breast cancer. This group of cancers affects 10 to 20 percent of breast cancer patients and is named because its growth is not driven by estrogen, progesterone, or the HER2 gene – all of which have targeted treatments.

    The study was a collaboration among the Florida labs of Derek Duckett and William R. Roush, both of TSRI, and John Cleveland, formerly of TSRI and currently at the Moffitt Cancer Center.

    “Our findings confirm that aberrant CK1δ regulation promotes tumor growth in breast cancers by activating the protein β-catenin,” said Dr. Duckett, an associate professor at Scripps Florida. “The best news, however, is that we have been able to treat CK1δ-expressing breast cancers with a highly selective and potent CK1δ inhibitor developed by Dr. Roush’s lab that triggers rapid tumor cell death.”

    At the beginning of the study, the team knew that the β-catenin protein was an oncogene in many cancers, but it was unclear why it was activated in these breast cancer types since they lacked typical mutations in those pathways. The researchers suspected the link could be overexpression of CK1δ. Their experiments showed that was indeed the case.

    To confirm the new target, the study used the Roush lab compound, called SR-3029. SR-3029 was remarkably successful at blocking the growth of tumors in both animal models and in studies with tumor tissue from breast cancer patients, and it caused few side effects.

    “SR-3029 removes β-catenin from cancer cells, killing the tumors,” explained Dr. Duckett. “This is an extraordinarily promising strategy for targeted treatment with SR-3029, especially in breast cancers that lack targeted treatment options.”

    “These results are just the tip of the iceberg,” added Dr. Roush, who is professor, associate dean and executive director of medicinal chemistry at TSRI. “Inhibitors such as SR-3029 are being studied in a host of different cancers, and we are hopeful this platform can be translated into clinical applications.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 4:46 pm on January 25, 2016 Permalink | Reply
    Tags: , Crouching Protein Hidden Enzyme, , Scripps Institute   

    From Scripps: “Crouching Protein, Hidden Enzyme” 

    Scripps
    Scripps Research Institute

    January 25, 2016
    Office of Communications
    Tel: 858-784-2666
    Fax: 858-784-8136
    press@scripps.edu

    Rpn11
    The new research shows the workings of a crucial molecular enzyme. In this image, the green glow in the structure denotes the location of the Rpn11 enzymatic active site in its inhibited conformation at the heart of the isolated lid complex.

    A new study led by scientists at The Scripps Research Institute (TSRI) and the University of California (UC), Berkeley shows how a crucial molecular enzyme starts in a tucked-in somersault position and flips out when it encounters the right target.

    The new findings, published recently in the journal eLife, give scientists a clearer picture of the process through which cells eliminate proteins that promote diseases such as cancer and Alzheimer’s.

    “Having an atomic-resolution structure and a better understanding of this mechanism gives us the ability to someday design therapeutics to combat cancer and neurodegeneration,” said TSRI biologist Gabriel Lander, who was co-senior of author of the study with Andreas Martin of UC Berkeley.

    Keeping Cells Healthy

    The new study sheds light on the proteasome, a molecular machine that serves as a recycling center in cells. Proteasomes break down spent or damaged proteins and can even eliminate harmful misfolded proteins observed in many diseases.

    The new research is the first study in almost 20 years to solve a large component of the proteasome at near-atomic resolution. Lander said the breakthrough was possible with recent advances in cryo-electron microscopy (EM), an imaging technique in which a sample is bombarded with an electron beam, producing hundreds of thousands of protein images that can be consolidated into a high-resolution structure.

    Using cryo-EM, scientists investigated part of the proteasome that contains a deubiquitinase enzyme called Rpn11. Rpn11 performs a crucial function called deubiquitination, during which it cleaves molecular tags from proteins scheduled for recycling in the proteasome. This is a key step in proteasomal processing—without Rpn11, the protein tags would clog the proteasome and the cell would die.

    From previous studies, scientists knew Rpn11 and its surrounding proteins latch onto the proteasome to form a sort of lid. “The lid complex wraps around the proteasome like a face-hugger in the movie ‘Alien,’” said Lander.

    The lid complex can also exist separately from the proteasome—which poses a potential problem. If Rpn11 cleaves tags from proteins that haven’t gotten to the proteasome yet, those proteins could skip the recycling stage and cause disease. Scientists had wondered how nature had solved this problem.

    A Guide for Future Therapies

    The study provides an answer, showing the lid complex as it floats freely in cells. In this conformation, Rpn11 is carefully nestled in the crook of surrounding proteins, stabilized and inactive.

    “There’s a sophisticated network of interactions that pin the Rpn11 deubiquitinase against neighboring subunits to keep it inhibited in the isolated proteasome lid,” explained Corey M. Dambacher, a researcher at TSRI at the time of the study and now a senior scientist at Omniome, Inc., who was first author of the study with TSRI Research Associate Mark Herzik Jr. and Evan J. Worden of UC Berkeley.

    “In order for Rpn11 to perform its job, it has to flip out of this inhibited conformation,” said Herzik.

    The new study also shows that, to flip out of the conformation at the proteasome, the proteins surrounding deubiquitinase pivot and rotate—binding to the proteasome and releasing the deubiquitinase active site from its nook.

    Lander called the system “finely tuned,” but said there may be ways to manipulate it. The study collaborators at UC Berkeley made small mutations to the proteins holding Rpn11 in position, and found that any small change will release the deubiquitinase, even when the lid is floating freely.

    Lander said the new understanding of the mechanism that activates Rpn11 could guide future therapies that remove damaged or misfolded proteins.

    “Accumulation of these toxic proteins can lead to diseases such as Parkinson’s and Alzheimer’s, as well as a variety of cancers,” Lander said. “If we can harness the proteasome’s ability to remove specific proteins from the cell, this gives us incredible power over cellular function and improves our ability to target certain cells for destruction.”

    Going forward, the researchers hope to use the same cryo-EM techniques to investigate other components of the proteasome—and figure out exactly how it recognizes and destroys proteins. “There’s still a lot to learn,” said Lander.

    For more information on the study, “Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition,” see http://elifesciences.org/content/early/2016/01/08/eLife.13027

    This research was supported by the Damon Runyon Cancer Research Foundation (grant DFS-#07-13), the Pew Scholars program, the National Institutes of Health (grants DP2 EB020402 and R01-GM094497), the Searle Scholars Program, the National Science Foundation CAREER Program (grant NSF-MCB-1150288), the Howard Hughes Medical Institute and a National Science Foundation Graduate Research Fellowship.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
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