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  • richardmitnick 3:02 pm on May 26, 2016 Permalink | Reply
    Tags: , , Scripps Institute, TSRI Scientists Discover Mechanism that Turns Mutant Cells into Aggressive Cancers   

    From Scripps: “TSRI Scientists Discover Mechanism that Turns Mutant Cells into Aggressive Cancers” 

    Scripps
    Scripps Research Institute

    Scientists at The Scripps Research Institute (TSRI) have caught a cancer-causing mutation in the act.

    A new study shows how a gene mutation found in several human cancers, including leukemia, gliomas and melanoma, promotes the growth of aggressive tumors.

    “We’ve found the mechanism through which this mutation leads to a scrambling of the genome,” said TSRI Associate Professor Eros Lazzerini Denchi, who co-led the study with Agnel Sfeir of New York University (NYU) School of Medicine. “That’s when you get really massive tumors.”

    The research, published* May 26, 2016 by the journal Cell Reports, also suggests a possible way to kill these kinds of tumors by targeting an important enzyme.

    A Puzzling Finding

    The researchers investigated mutations in a gene that codes for the protein POT1. This protein normally forms a protective cap around the ends of chromosomes (called telomeres), stopping cell machinery from mistakenly damaging the DNA there and causing harmful mutations.

    POT1 is so critical that cells without functional POT1 would rather die than pass on POT1 mutations. Stress in these cells leads to the activation of an enzyme, called ATR, that triggers programmed cell death.

    Knowing this, scientists in recent years were surprised to find recurrent mutations affecting POT1 in several human cancers, including leukemia and melanoma.

    “Somehow those cells found a way to survive—and thrive,” said Lazzerini Denchi. “We thought that if we could understand how that happens, maybe we could find a way to kill those cells.”

    It Takes Two to Tango

    Using a mouse model, the researchers found that mutations in POT1 lead to cancer when combined with a mutation in a gene called p53.

    “The cells no longer have the mechanism for dying, and mice develop really aggressive thymic lymphomas,” said Lazzerini Denchi.

    P53, a well-known tumor suppressor gene, is a cunning accomplice. When mutated, it overrides the protective cell death response initiated by ATR. Then, without POT1 creating a protective cap, the chromosomes are fused together and the DNA is rearranged, driving the accumulation of even more mutations. These mutant cells go on to proliferate and become aggressive tumors.

    The findings led the team to consider a new strategy for killing these tumors.

    Scientists know that all cells—even cancer cells—will die if they have no ATR. Since tumors with mutant POT1 already have low ATR levels, the researchers think a medicine that knocks out the remaining ATR could kill tumors without affecting healthy cells. “This study shows that by looking at basic biological questions, we can potentially find new ways to treat cancer,” said Lazzerini Denchi.

    The researchers plan to investigate this new therapeutic approach in future studies.

    In addition to Lazzerini Denchi and Sfeir, authors of the study, “Telomere replication stress induced by POT1 inactivation accelerates tumorigenesis,” were Angela Beal and Nidhi Nair of TSRI; Alexandra M. Pinzaru, Aaron F. Phillips, Eric Ni and Timothy Cardozo of the NYU School of Medicine; Robert A. Hom and Deborah S. Wuttke of the University of Colorado; and Jaehyuk Choi of Northwestern University.

    The study was supported by the National Institutes of Health (grants AG038677, CA195767 and GM059414), a NYSTEM institutional training grant (C026880), a scholarship from the California Institute for Regenerative Medicine, a Ruth L. Kirschstein National Research Service Award (GM100532), The V Foundation for Cancer Research, two Pew Stewart Scholars Awards and the Novartis Advanced Discovery Institute.

    *Science paper:
    Telomere Replication Stress Induced by POT1 Inactivation Accelerates Tumorigenesis

    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 8:47 pm on May 20, 2016 Permalink | Reply
    Tags: , , Scripps Institute   

    From Scripps: “Researchers Pioneer a Breakthrough Approach to Breast Cancer Treatment” 

    Scripps
    Scripps Research Institute

    May 23, 2016
    Eric Sauter

    In a development that could lead to a new generation of drugs to precisely treat a range of diseases, scientists from the Florida campus of The Scripps Research Institute (TSRI) have for the first time designed a drug candidate that decreases the growth of tumor cells in animal models in one of the hardest to treat cancers—triple negative breast cancer.

    “This is the first example of taking a genetic sequence and designing a drug candidate that works effectively in an animal model against triple negative breast cancer,” said TSRI Professor Matthew Disney.

    1
    “The study represents a clear breakthrough in precision medicine, as this molecule only kills the cancer cells that express the cancer-causing gene—not healthy cells,” says Professor Matthew Disney. (Photo by James McEntee.)

    The study*, published online ahead of print the week of May 9, 2016, by the journal Proceedings of the National Academy of Sciences, demonstrates that the Disney lab’s compound, known as Targaprimir-96, triggers breast cancer cells to kill themselves via programmed cell death by precisely targeting a specific RNA that ignites the cancer.

    Short-Cut to Drug Candidates

    While the goal of precision medicine is to identify drugs that selectively affect disease-causing biomolecules, the process has typically involved time-consuming and expensive high-throughput screens to test millions of potential drug candidates to identify those few that affect the target of interest. Disney’s approach eliminates these screens.

    The new study uses the lab’s computational approach called Inforna, which focuses on developing designer compounds that bind to RNA folds, particularly microRNAs.

    MicroRNAs are short molecules that work within all animal and plant cells, typically functioning as a “dimmer switch” for one or more genes, binding to the transcripts of those genes and preventing protein production. Some microRNAs have been associated with diseases. For example, microRNA-96, which was the target of the new study, promotes cancer by discouraging programmed cell death, which can rid the body of cells that grow out of control.

    In the new study, the drug candidate was tested in animal models over a 21-day course of treatment. Results showed decreased production of microRNA-96 and increased programmed cell death, significantly reducing tumor growth. Since targaprimir-96 was highly selective in its targeting, healthy cells were unaffected.

    In contrast, Disney noted, a typical cancer therapeutic targets and kills cells indiscriminately, often leading to side effects that can make these drugs difficult for patients to tolerate.

    “In the future we hope to apply this strategy to target other disease-causing RNAs, which range from incurable cancers to important viral pathogens such as Zika and Ebola,” added Research Associate Sai Pradeep Velagapudi, the first author of the study and a member of the Disney lab.

    [Alex Perryman, formerly at Scripps, a veteran of the Scripps project FightAids@home on World Community Grid and now at Rutgers University is leading the new WCG project OpenZika. WCG also has OutsmartEbolaTogether at Scripps]

    WCGLarge

    Rutgers Open Zika

    Outsmart Ebola Together

    2
    “In the future we hope to apply this strategy to target other disease-causing RNAs, which range from incurable cancers to important viral pathogens such as Zika and Ebola,” says Research Associate Sai Pradeep Velagapudi.

    In addition to Disney and Velagapudi, authors of the study, “Design of a Small Molecule Against an Oncogenic Non-coding RNA,” were Michael D. Cameron, Christopher L. Haga, Laura H. Rosenberg, Marie Lafitte, Derek Duckett and Donald G. Phinney of TSRI.

    The work was supported by the National Institutes of Health (R01GM9455) and The Nelson Fund for Therapeutic Development.

    *Science paper:
    Design of a small molecule against an oncogenic noncoding RNA

    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 10:46 am on May 10, 2016 Permalink | Reply
    Tags: , , Scripps Florida Scientists Design Potent Therapeutic 'Warheads' That Target Cancer Cells, Scripps Institute   

    From Scripps: “Scripps Florida Scientists Design Potent Therapeutic ‘Warheads’ That Target Cancer Cells” 

    Scripps
    Scripps Research Institute

    May 9, 2016

    In a pair of related studies, chemists from the Florida campus of The Scripps Research Institute (TSRI) have identified and designed dozens of molecular “warheads” that not only can detect a key biomarker of cancer, but also could be developed into a potent new class of drug candidates for a range of diseases.

    A number of these molecules are already “hidden” in drugs approved by the U.S. Food and Drug Administration (FDA), raising the possibility that these widely used pharmaceuticals could be made even more effective using more potent/selective covalent inhibitors or “warheads.”

    The studies, which were published recently in the journals Chemical Science and Chemical Communication, were led by TSRI Associate Professor Kate Carroll.

    The molecules in question are known as “nucleophiles” (literally, nucleus lovers), which share their electrons with “electrophiles” (literally, electron lovers) and serve as their atomic dance partners. This sharing of electrons creates an interaction known as a covalent bond, which some consider the fundamental basis of chemical reactivity.

    Electrophiles have been available to the scientific community for decades for use as tools to probe levels of cysteine sulfenic acid—a marker for cancer and other diseases—and to install as “warheads” or covalent modifiers in drugs that target high levels of sulfenic acid in cells.

    The downside of electrophiles is that they compete with high concentrations of off-target nucleophiles in the cell, such as glutathione. In addition, this class of covalent inhibitors indiscriminately targets the protein in healthy and diseased cells. “To counteract this effect, our complementary approach would use nucleophile ‘warheads’ attached to a binding scaffold that would target sulfenic acid on therapeutically important proteins in unhealthy cells under oxidative stress,” said Carroll.

    To produce a library of “designer” nucleophiles with far greater reactivity, Carroll and her colleague, Senior Research Associate Vinayak Gupta, developed a unique screen. So far, some of the nucleophiles they identified possess more than 200 times the current standard for sulfenic acid probes.

    “We now have about 150 of these ‘warheads’ in our library,” Carroll said.

    While the greater interest in the scientific community has been in electrophiles, the TSRI team also examined previously unidentified nucleophilic functional groups, such as those within the Pfizer rheumatoid arthritis drug tofacitinib (XELJANZ®).

    “The nucleophiles we identified in this study represent the first covalent strategy to target sulfenic acid that should be highly enabling for the drug discovery community,” Gupta said. “Moreover, our findings that tofacitinib reacts robustly with sulfenic acid shows that ‘warheads’ or other functional groups in these drugs may indeed have new or alternative mechanisms of action.”

    Carroll added, “Tofacitinib may have multiple modes of action that include a nucleophile targeting cysteine sulfenic acid in the active site of JAK kinases. If the nucleophile contributes positively to therapeutic outcome, it might be possible to optimize that chemical property and make the drug more effective.”

    Carroll says she uncovers more instances of nucleophiles “hidden in plain sight” every day, suggesting that nucleophiles may, in fact, be unsung central players in these reactions.

    The studies, Profiling the Reactivity of Cyclic C-Nucleophiles towards Electrophilic Sulfur in Cysteine Sulfenic Acid, and Rational Design of Reversible and Irreversible Cysteine Sulfenic Acid-Targeted Linear C-Nucleophiles, were published in Chemical Science and Chemical Communications, respectively.

    The work was supported by the National Institutes of Health (grant numbers R01 GM102187 and R01 CA174864).

    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 1:51 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.

     
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