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  • richardmitnick 2:49 pm on January 31, 2017 Permalink | Reply
    Tags: , Scripps Institute   

    From Scripps: “New Method Could Turbocharge Drug Discovery, Protein Research” 

    Scripps
    Scripps Research Institute

    January 30, 2017
    Mo writer credit

    A team led by scientists at The Scripps Research Institute (TSRI) has developed a versatile new method that should enhance the discovery of new drugs and the study of proteins.

    The new method enables researchers to quickly find small molecules that bind to hundreds of thousands of proteins in their native cellular environment. Such molecules, called ligands, can be developed into important tools for studying how proteins work in cells, which may lead to the development of new drugs. The method can be used even without prior knowledge of protein targets to discover ligand molecules that disrupt a biological process of interest—and to quickly identify the proteins to which they bind.

    “This ,” said co-lead author Christopher G. Parker, a research associate in the laboratory of TSRI Professor Benjamin F. Cravatt, chairman of the Department of Chemical Biology.

    This research was published ahead of print recently in the journal Cell.

    1
    Authors of the new study included (left to right) TSRI’s Andrea Galmozzi, Christopher Parker, Benjamin Cravatt and Enrique Saez. (Photo by Madeline McCurry-Schmidt.)

    Finding New Partners for Un-targetable Proteins

    About 25,000 proteins are encoded in the human genome, but public databases list known ligands for only about 10 percent of them. Biologists have long sought better tools for exploring this terra incognita.

    The new method involves the development of a set of small, but structurally varied, candidate ligand molecules known as “fragments.” Each candidate ligand is modified with a special chemical compound so that, when it binds with moderate affinity to a protein partner, it can be made to stick permanently to that partner by a brief exposure to UV light. A further modification provides a molecular handle by which scientists can grab and isolate these ligand-protein pairs for analysis.

    For an initial demonstration, the team assembled a small “library” of candidate ligands whose structural features include many that are found in existing drugs. By applying just 11 of them to human cells, the researchers identified more than 2,000 distinct proteins that had bound to one or more of the ligands.

    These ligand-bound proteins include many from categories—such as transcription factors—that previously had been considered “un-ligandable” and therefore un-targetable with drugs. In fact, only 17 percent of these proteins have known ligands, according to the widely used DrugBank database.

    The researchers used further methods to identify, for many ligand-protein interactions, the site on the protein where the coupling occurred.

    The candidate ligands initially used to screen for protein binding partners are generally too small to bind to their partners tightly enough to disrupt their functions in cells. But the team showed that, in multiple cases, that these initial small (“fragment”) ligands could be developed into larger, more complex molecules that display higher-affinity interactions and disrupt their protein partner’s functions.

    A New Type of Functional Screen

    For a final demonstration, collaborating chemists at Bristol-Myers Squibb helped create a library of several hundred slightly more complex candidate ligands. With TSRI colleagues Associate Professor Enrique Saez and co-first author Research Associate Andrea Galmozzi, the team then tested these ligands to find any that could promote the maturation of fat cells (adipocytes)—a process that in principle can alleviate the insulin resistance that leads to type 2 diabetes.

    Traditional functional screens of this type do not pinpoint the proteins or other molecules through which the effect on the cell occurs. But with this new discovery method, the researchers quickly found not only a ligand that strongly promotes adipocyte maturation but also its binding partner, PGRMC2, a protein about which little was known.

    “We found a new ‘druggable’ pathway, and we also seem to have uncovered some new biology—despite the fact that adipocyte maturation and other diabetes-related pathways have been studied a lot already,” Parker said.

    “With this method, we look forward to exploring much more thoroughly the druggability of human proteins and accelerating investigations of protein biology,” Cravatt added.

    In addition to Parker, Cravatt, Saez and Galmozzim authors of the study, “Ligand and Target Discovery by Fragment-Based Screening in Human Cells,” included TSRI’s Yujia Wang, Kenji Sasaki, Christopher Joslyn and Arthur S. Kim; Bruno Correia of Ecole Polytechnique Federal in Lausanne, Switzerland; and Cullen Cavallaro, Michael Lawrence and Stephen Johnson of Bristol-Myers Squibb.

    The work was supported by grants from the National Institutes of Health (DK099810; CA132630; 1S10OD16357), an American Cancer Society Postdoctoral Fellowship and a fellowship from the American Heart Association.

    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 2:03 pm on January 23, 2017 Permalink | Reply
    Tags: , FAAH, , HIVE, , Scripps Institute,   

    From FAAH at WCG: “Virtual Screening of the HIV-1 Mature Capsid Protein” 

    New WCG Logo

    WCGLarge

    World Community Grid (WCG)

    faah-1-new

    faah-hive

    Scripps Institute

    This webpage is dedicated to the virtual screening of the HIV-1 capsid protein in her mature form. This project is part of the HIVE Center and the FA@H initiative in collaboration with IBM and their World Community Grid (WCG).

    People involved in the project come from the Olson Lab in The Scripps Research Institute, and from all over the world as volunteers of the WCG. Meet them here.

    FightAidsOlsonLab@home

    For any question about the project or this webpage, please contact
    Dr. Pierrick Craveur : pcraveur@scripps.edu

    Background

    During the maturation of the HIV virus, the HIV-1 capsid protein (CA) assembles with thousands of copies to forms the capsid core [ref 1] with a characteristic conical shape (see Figure 1 and Figure 2C). This core encloses the RNA viral genome. Upon the entry of the HIV in host cells, the capsid core is released into the cytoplasm, and it dissociates in connection with the reverse transcription in a not completely understood process. This leads to the importation of DNA viral genome in the host cell’s nucleus, where it is integrated in the host DNA to finalize the infection.

    2
    Figure 1: The early phase of the HIV-1 replication cycle.
    (credit: Nature Reviews Microbiology 13, 471–483 (2015) | doi:10.1038/nrmicro3503)

    The critical role of CA protein, in early and late stages of the viral replication life cycle, has led to recent efforts on drug development, targeting the mature form of the protein. Currently, none of these molecules are used in clinic, and some face natural polymorphism and resistant mutations [ref 2]. Therefore, continued development of drugs targeting the CA protein is still needed.

    The critical role of CA protein, in early and late stages of the viral replication life cycle, has led to recent efforts on drug development, targeting the mature form of the protein. Currently, none of these molecules are used in clinic, and some face natural polymorphism and resistant mutations [ref 2]. Therefore, continued development of drugs targeting the CA protein is still needed.

    3
    Figure 2: The HIV-1 mature capsid assembly.
    (credit: Pierrick Craveur)

    Different level of the capsid protein structure

    CA protein consist of a sequence of 231 amino acids which folds into 3 different domains (Figure 2A): The N-terminal domain (N-ter), the linker, and the C-terminal domain (C-ter). This protein chain complexes with other chains to form hexamers (Figure 2B) or pentamers; which assemble together to form the fullerene-cone shape of the capsid core (Figure 2C). There are several models of the core assembly, but all are composed of ~200 hexamers, and exactly 12 pentamers.

    High Throughput Virtual Screening

    The FightAIDS@Home team is working with World Community Grid to find active compounds which could attach to the CA proteins and mediate the assembly of the capsid core. This computational experiment will be performed using the docking software AutoDock VINA [ref 3].
    Thanks to the volunteers, around 2 million molecules will be screened across ~50 conformations of the capsid protein, and hopefully lead to a reduced selection of molecules. This will be the starting point of a drug discovery process targeting the HIV-1 capsid protein.
    This computational experiment will be performed using the docking software AutoDock VINA [ref 3].
    With the support of our collaborators from the HIV Interaction and Viral Evolution (HIVE), experimental biding assays and infectivity assays will be conducted to determine if the selected compounds could be optimized as a promising drug candidate.

    4
    Figure 3: The four pockets of interest.
    (credit: Pierrick Craveur)

    Four pockets of interest

    Based on X-ray structures of CA protein, models of the core, and computational analysis of their flexibility, four pockets of interest have been selected on the surface of the hexamer assembly (see Figure 3).
    These pockets involve either one monomer (as pocket 2 along the linker domain), at the interface of two monomers (pocket 1 & 4), or at the six-fold interface (pocket 3).
    Mutagenesis experiments revealed that core stability is fine-tuned to allow ordered disassembly during early stage of virus replication cycle [ref 4]. This is why selection of compounds will be done either for molecules which could stabilize or destabilize the hexamer; assuming that both actions could have impacts on the equilibrium of the core.

    References

    Briggs, J. A. and H. G. Krausslich (2011). “The molecular architecture of HIV.” J Mol Biol 410(4): 491-500.
    Thenin-Houssier, S. and S. T. Valente (2016). “HIV-1 Capsid Inhibitors as Antiretroviral Agents.” Curr HIV Res 14(3): 270-282.
    Trott, O. and A. J. Olson (2010). “AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.” J Comput Chem 31(2): 455-461.
    Forshey, B. M., U. von Schwedler, et al. (2002). “Formation of a human immunodeficiency virus type 1 core of optimal stability is crucial for viral replication.” J Virol 76(11): 5667-5677.

    See the full article here.

    Please help promote STEM in your local schools.
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    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”
    WCG projects run on BOINC software from UC Berkeley.
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    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

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    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

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    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-

    FightAIDS@home Phase II

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  • richardmitnick 3:10 pm on January 20, 2017 Permalink | Reply
    Tags: , , , Scripps Institute, Telomere length, TZAP   

    From Scripps: “Scientists Discover Master Regulator of Cellular Aging’ 

    Scripps
    Scripps Research Institute

    January 23, 2017
    Madeline McCurry-Schmidt

    1
    “This protein sets the upper limit of telomere length,” says Associate Professor and senior author Eros Lazzerini Denchi (left), pictured here with study first author Graduate Student Julia Su Zhou Li. (Photo by Madeline McCurry-Schmidt.)

    Scientists at The Scripps Research Institute (TSRI) have discovered a protein that fine-tunes the cellular clock involved in aging.

    This novel protein, named TZAP, binds the ends of chromosomes and determines how long telomeres, the segments of DNA that protect chromosome ends, can be. Understanding telomere length is crucial because telomeres set the lifespan of cells in the body, dictating critical processes such as aging and the incidence of cancer.

    “Telomeres represent the clock of a cell,” said TSRI Associate Professor Eros Lazzerini Denchi, corresponding author of the new study, published in the journal Science [link is below]. “You are born with telomeres of a certain length, and every time a cell divides, it loses a little bit of the telomere. Once the telomere is too short, the cell cannot divide anymore.”

    Naturally, researchers are curious whether lengthening telomeres could slow aging, and many scientists have looked into using a specialized enzyme called telomerase to “fine-tune” the biological clock. One drawback they’ve discovered is that unnaturally long telomeres are a risk factor in developing cancer.

    “This cellular clock needs to be finely tuned to allow sufficient cell divisions to develop differentiated tissues and maintain renewable tissues in our body and, at the same time, to limit the proliferation of cancerous cells,” said Lazzerini Denchi.

    In this new study, the researcher found that TZAP controls a process called telomere trimming, ensuring that telomeres do not become too long.

    “This protein sets the upper limit of telomere length,” explained Lazzerini Denchi. “This allows cells to proliferate—but not too much.”

    For the last few decades, the only proteins known to specifically bind telomeres were the telomerase enzyme and a protein complex known as the Shelterin complex. The discovery TZAP, which binds specifically to telomeres, was a surprise since many scientists in the field believed there were no additional proteins binding to telomeres.

    “There is a protein complex that was found to localize specifically at chromosome ends, but since its discovery, no protein has been shown to specifically localize to telomeres,” said study first author Julia Su Zhou Li, a graduate student in the Lazzerini Denchi lab.

    “This study opens up a lot of new and exciting questions,” said Lazzerini Denchi.

    In addition to Lazzerini Denchi and Li, authors of the study, TZAP: a telomere-associated protein involved in telomere length control, were Tatevik Simavorian, Cristina Bartocci and Jill Tsai of TSRI; Javier Miralles Fuste of the Salk Institute for Biological Studies and the University of Gothenburg; and Jan Karlseder of the Salk Institute for Biological Studies.

    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 1:59 pm on January 4, 2017 Permalink | Reply
    Tags: , Mass spectrometry, Proteases, Scripps Florida Scientists Expand Toolbox to Study Cellular Function, Scripps Institute   

    From Scripps: “Scripps Florida Scientists Expand Toolbox to Study Cellular Function” 

    Scripps
    Scripps Research Institute

    January 4, 2017
    No writer credit

    Scientists on the Florida campus of The Scripps Research Institute (TSRI) have developed a new tool for studying the molecular details of protein structure.

    Their new study, published recently in the journal Proceedings of the National Academy of Sciences, explores how evolution can be used to discover new and useful enzyme tools, called proteases. Proteases cleave proteins into smaller peptide pieces that scientists can then analyze to determine the identity of the protein and whether a cell has made chemical changes to the protein that might alter its function.

    The new protease developed in the study helps shed light on these chemical changes, called post-translational modifications. Post-translational modifications are alterations made to proteins after the proteins are translated from RNA.

    “We have to observe these protein modifications directly through chemical analysis; we can’t read them out of DNA sequence,” explained study senior author Brian M. Paegel, associate professor at TSRI.

    These modifications can dramatically alter a protein’s stability and function, and unregulated modification can lead to disease, such as cancer. Therefore, understanding the nature and location of these modifications can be critical in the early phases of drug discovery.

    Scientists currently rely on a technique called mass spectrometry to study post-translational modifications. Mass spectrometry analyzes peptides to see if their mass changes—a bit like zooming in on that protein to see hidden details. An unexpected change in mass can indicate the occurrence of a post-translational modification.

    Many scientists today use a protease called trypsin to break proteins into peptides. Because there are few other proteases available for mass spectrometry, trypsin has become the workhorse of the field. However, Paegel explained, it’s luck of the draw if trypsin generates a peptide with a modified site. So Paegel and co-workers thought it would be useful to have a new tool that cleaved directly at the modified site.

    To solve this problem, Paegel developed a new trypsin “mutant” using a technique called “directed evolution.” The scientists created many thousands of trypsin mutants and tested each mutant for its ability to cut a protein at modified sites. They discovered a mutant that could cut proteins at citrulline, which is one type of modification.

    Paegel believes this new approach could be useful for mapping a wider range of post-translational modifications, and he hopes to use directed evolution to discover proteases that target many other post-translational modifications. “I think we’re on the brink of an explosion of new tools for mass spectrometry,” he said.

    In addition to Paegel, authors of the study, “Evolution of a mass spectrometry-grade protease with PTM-directed specificity,” were Duc. T. Tran (first author), Valerie Cavett, Vuong Q. Dang and Héctor L. Torres of TSRI.

    This study was supported by a National Institutes of Health’s Director’s New Innovator Award (grant OD008535) and a National Science Foundation Research Experiences for Undergraduates Grant (1359369).

    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 8:17 am on September 30, 2016 Permalink | Reply
    Tags: , , , Scientists find evidence that life on Earth didn't only originate from RNA, Scripps Institute   

    From Science Alert: “Scientists find evidence that life on Earth didn’t only originate from RNA” 

    ScienceAlert

    Science Alert

    29 SEP 2016
    FIONA MACDONALD

    1
    NASA Goddard Space Flight Centre/Flickr.

    It’s not as simple as it seems.

    Scientists have just put forward an alternate hypothesis for how life originated on Earth – suggesting that RNA alone didn’t kickstart the process.

    Right now, the leading explanation for how life rose up out of Earth’s primordial soup some 3.8 billion years ago is the ‘RNA world’ hypothesis, which proposes that RNA came first, and eventually created DNA, which went on to form complex life as we know it.

    But now a team of chemists from the Scripps Research Institute in California has found evidence that RNA wouldn’t have been able to sustainably give rise to DNA, leading them to suggest that the two molecules might have actually formed at the same time.

    “Even if you believe in a RNA-only world, you have to believe in something that existed with RNA to help it move forward,” said lead researcher Ramanarayanan Krishnamurthy.

    “Why not think of RNA and DNA rising together, rather than trying to convert RNA to DNA by means of some fantastic chemistry at a prebiotic stage?”

    If you need a bit of a refresher on the RNA world hypothesis, RNA (or ribonucleic acid) is widely known as the “older molecular cousin” of DNA (deoxyribonucleic acid).

    While they share a pretty similar structure – RNA looks like one side of DNA’s ladder – RNA is more brittle and less flexible than DNA, which is most likely why DNA ended up forming our genes.

    But it’s widely believed that RNA, despite its faults, came first, with many scientists suggesting that it was the first self-replicating molecule on Earth.

    The RNA world hypothesis states that RNA self-assembled from ancient Earth’s bubbling hot stew of particles, and went on to turn amino acids into proteins and enzymes. Eventually, those enzymes helped RNA to produce DNA, which led to complex life.

    That’s the short story anyway. Many researchers think that there would have also been cases where RNA nucleotides – the little building blocks of RNA – would have mixed with the backbone that forms DNA, creating mixed ‘chimera’ strands.

    Those chimeras would have been a crucial step in the transition from RNA to DNA, and it’s this step that the chemists behind the latest study have an issue with.

    In their research, they tested whether RNA and DNA could realistically share the same backbone, and showed that, when the two molecules are blended, they were highly unstable.

    “We were surprised to see a very deep drop in what we would call the ‘thermal stability’,” said Krishnamurthy.

    That means these chimeras in the RNA world would have most likely died off in favour of more stable RNA molecules, or failed to self-replicate, he explains.

    This isn’t the first time this has been demonstrated – Nobel laureate Jack Szostak from Harvard University has also shown a loss of function when RNA mixed with DNA.

    Even in today’s cells, if RNA nucleotides accidentally join a DNA strand, enzymes rush in to fix the mistake – and 3.8 billion years ago, RNA wouldn’t have had that self-correct mechanism.

    “The transition from RNA to DNA would not have been easy without mechanisms to keep them separate,” said Krishnamurthy.

    That evidence supports the idea that RNA and DNA actually arose at the same time, potentially from similar ingredients in Earth’s primordial soup, the researchers conclude in Angewandte Chemie.

    They’re not the first team to put forward this idea, but their findings provide new evidence to support this alternate hypothesis for the origins of life.

    If their findings are confirmed, it doesn’t necessarily mean that RNA didn’t give rise to DNA – but it’s likely that DNA evolved, at least in some primitive state, earlier than we’d predicted.

    Unfortunately, without a time machine, it’s unlikely we’ll ever really know what went on back at the dawn of life on Earth. But by trying to figure it out, we might have a better shot of predicting where we might find life elsewhere in the Universe.

    See the full article here .

    Please help promote STEM in your local schools.

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  • richardmitnick 9:36 am on September 15, 2016 Permalink | Reply
    Tags: , How a New Drug Could Treat Both Diabetes and Bone Loss, , New compound SR10171, Scripps Institute, Type II diabetes and bone loss   

    From Scripps: “How a New Drug Could Treat Both Diabetes and Bone Loss” 

    Scripps
    Scripps Research Institute

    September 2016
    No writer credit

    In addition to its more obvious ills, type 2 diabetes is a condition closely associated with bone fractures – increasing the risk of fractures twofold. To make matters worse, certain anti-diabetic drugs further increase this risk, particularly in postmenopausal women, severely limiting their treatment options.

    But now, a team of scientists at on the Florida campus of The Scripps Research Institute (TSRI), co-led by TSRI’s Patrick R. Griffin and B. Lecka-Czernik, a professor at the University of Toledo, has shown that a new class of drug candidates developed at TSRI increase bone mass by expanding bone formation (deposition of new bone) and bone turnover (a normal process of bone replacement). The discovery could lead to new therapies for type 2 diabetes and bone loss. A proper balance of these two processes is critical to healthy bone maintenance, and this balance is frequently negatively affected in diabetic patients.

    The result is a new dual-targeting drug candidate – or, as Dr. Griffin describes it, “one drug addressing multiple therapeutic indications” – which could treat both diabetes and bone disease. The compound has been referenced as “SR10171.”

    Diabetes affects more than 29 million people in the United States, according to a 2012 report from the American Diabetes Association. In 2013, estimated direct medical costs of the disease totaled $176 billion.

    Over the past decade, Dr. Griffin and his colleague, TSRI Associate Professor Theodore Kamenecka, have focused on the details of molecules that increase sensitivity to insulin (a hormone that regulates blood sugar). Using newly discovered information, the researchers made significant advances in developing a family of drug candidates that target a receptor known as peroxisome proliferator-activated receptors gamma (PPARγ), a key regulator of stem cells controlling bone formation and bone resorption and a master regulator of fat.

    Anti-diabetic drugs known as glitazones (TZDs) target the PPARγ protein, but that interaction leads to severe bone loss and increased fractures. Stem cells in the bone marrow can differentiate either into bone cells or fat cells, and the glitazones drive them to fat at the expense of bone.

    But SR10171 is designed to avoid this troubling outcome. In animal models treated with the compound, fat formation in the bone marrow was successfully blocked independent of their metabolic state (healthy or diabetic).

    “Using structural biology techniques and rational design synthetic chemistry, SR10171 was constructed to engage the PPARγ protein in a unique way possessing an optimal balance with the receptor’s other family member, PPARa, to treat diabetes and, at the same time, improve bone health,” Dr. Griffin said. “This targeted polypharmacological approach demonstrates that the target isn’t the problem if you target it correctly.”

    The compound increases bone mass by protecting and increasing the activity of bone cells in various stages of normal bone maintenance, utilizing mechanisms that overlap those that regulate whole-body energy metabolism.

    “SR10171 improves bone mass regardless of body mass index, normal to obese,” Dr. Griffin added. “So you could use such a drug to treat osteoporosis whether patients are diabetic or not.”

    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 1:26 pm on September 13, 2016 Permalink | Reply
    Tags: , , , , Scripps Institute   

    From Scripps: “TSRI Scientists Discover Antibodies that Target Holes in HIV’s Defenses” 

    Scripps
    Scripps Research Institute

    September 12, 2016

    New Findings Could Lead to New AIDS Vaccine Candidates

    A new study from scientists at The Scripps Research Institute (TSRI) shows that “holes” in HIV’s defensive sugar shield could be important in designing an HIV vaccine.

    It appears that antibodies can target these holes, which are scattered in HIV’s protective sugar or “glycan” shield, and the question is now whether these holes can be exploited to induce protective antibodies.

    “It’s important now to evaluate future vaccine candidates to more rapidly understand the immune response they induce to particular glycan holes and learn from it,” said TSRI Professor Dennis R. Burton, who is also scientific director of the International AIDS Vaccine Initiative (IAVI) Neutralizing Antibody Center and of the National Institutes of Health’s Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID) at TSRI.

    The study, published recently in the journal Cell Reports, was co-led by Burton, TSRI Associate Professor Andrew Ward, also of CHAVI-ID, and Rogier W. Sanders of the University of Amsterdam and Cornell University.

    A Clue to Stopping HIV

    Every virus has a signature structure, like the architecture of a building. By solving these structures, scientists can put together a blueprint showing where HIV is vulnerable to infection-blocking antibodies.

    In the 1990s, scientists discovered that HIV can have random holes in its protective outer shell of glycan molecules. Until now, however, scientists weren’t sure if antibodies could recognize and target these holes.

    Researchers at Cornell and TSRI had previously designed a stabilized version of an important HIV protein, called the envelope glycoprotein (Env) trimer, to prompt rabbit models to produce antibodies against the virus. In the new study, the plan was to reveal HIV’s vulnerabilities by examining where the antibodies bound the virus.

    “From work on HIV-positive individuals, we knew that the best way to understand an antibody response is to isolate the individual antibodies and study them in detail,” said Laura McCoy, a TSRI, IAVI and CHAVI-ID researcher now at University College London, who served as co-first author of the study with TSRI Senior Research Associate Gabriel Ozorowski, also of TSRI and CHAVI-ID, and Marit J. van Gils of the University of Amsterdam.

    To their surprise, when the researchers examined the rabbits’ antibodies, they found three rabbits had produced antibodies that targeted the same hole in Env. It appeared that antibodies could indeed target holes in the glycan shield.

    “This opened up a whole new concept,” said Ozorowski.

    If the immune system was targeting this hole—preferring it to other vulnerable spots on Env—maybe holes would be especially important in designing vaccine candidates.

    Toward Better Antibodies

    By analyzing the genetic sequences of thousands of strains of HIV, the researchers found that 89 percent of strains appear to have a targetable hole in the Env. The virus has a defense mechanism though—it quickly mutates to fill in these gaps.

    The researchers speculate that future vaccines might prompt the immune system to create antibodies to target holes. “Targeting a hole could help the immune system get its foot in the door,” Ozorowski said. Alternatively, the holes may prove a distraction and should be filled in so the immune system can focus on targeting better sites for neutralizing the virus.

    Burton said researchers must investigate the different possibilities, but he emphasized that this new understanding of glycan holes could help researchers narrow down the field of molecules needed in potential HIV vaccines.

    Ward added that this same method of “rational” vaccine design—where researchers use a virus’s precise molecular details to prompt the immune system to produce specific antibodies—can also be applied to efforts to fight other viruses, such as influenza and Ebola viruses.

    In addition to Burton, Ward, Sanders, McCoy, Ozorowski and van Gils, authors of the study, “Holes in the glycan shield of the native HIV envelope are a target of trimer-elicited neutralizing antibodies,” were Terrence Messmer, Bryan Briney, James E. Voss, Daniel W. Kulp, Devin Sok, Matthias Pauthner, Sergey Menis and Jessica Hsueh of TSRI, IAVI and CHAVI-ID; Christopher A. Cottrell, Jonathan L. Torres and Ian A. Wilson of TSRI and CHAVI-ID; Matthew S. Macauley of TSRI; and William R. Schief of TSRI, IAVI, CHAVI-ID and the Ragon Institute.

    This study was supported by CHAVI-ID (grant UM1AI100663), the National Institutes of Health’s HIV Vaccine Research and Design (HIVRAD) Program (grant P01 AI110657), the IAVI Neutralizing Antibody Center and Collaboration for AIDS Vaccine Discovery (CAVD, grants OPP1084519 and OPP1115782), a Marie-Curie Fellowship (FP7-PEOPLE-2013-IOF), the Aids Fonds Netherlands (grant 2012041), EMBO (grant ASTF260-2013), the Netherlands Organization for Scientific Research (grant 917.11.314) and the European Research Council (grant ERC-StG- 2011-280829-SHEV).

    See the full article here .

    YOU CAN HELP IN THE FIGHT AGAINST HIV/AIDS FROM THE COMFORT OF YOUR EASY CHAIR.

    The Fight AIDS at home (FAAH@home) Phase II project is now running at World Community Grid (WCG) From Scripps Research Institute.

    Scripps

    FAAH Phase II

    WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the FAAH@home Phase II project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

    WCGLarge

    BOINCLarge

    MyBOINC

    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 12:39 pm on September 9, 2016 Permalink | Reply
    Tags: , , , , Scripps Institute   

    From Scripps: “Team Harnesses Antibody Evolution on the Path to an AIDS Vaccine” 

    Scripps
    Scripps Research Institute

    September 12, 2016
    Madeline McCurry-Schmidt

    1
    The new work shows the immune system can be prompted to mimic and accelerate a rare natural process during which antibodies slowly evolve to become better and better at targeting the constantly mutating HIV virus. Shown here is the molecule eOD-GT8 60mer, used in the team’s reductionist strategy.

    A series of new studies led by scientists at The Scripps Research Institute (TSRI) and the International AIDS Vaccine Initiative (IAVI) describe a potential vaccination strategy to jump-start the selection and evolution of broadly effective antibodies to prevent HIV infection. The researchers plan to test this strategy in an upcoming human clinical trial.

    The new studies, published September 8, 2016, in the journals Cell and Science, showed the immune system can be prompted to mimic and accelerate a rare natural process during which antibodies slowly evolve to become better and better at targeting the constantly mutating HIV virus.

    “Although we still have a long way to go, we’re making really good progress toward a human vaccine,” said William Schief, professor at TSRI and director of vaccine design for IAVI’s Neutralizing Antibody Center (NAC) at TSRI, whose lab developed many of the vaccine proteins tested in these studies.

    Schief co-led several of the new studies with TSRI Professor David Nemazee; Dennis Burton, James & Jessie Minor chair of the TSRI Department of Immunology and Microbial Science and scientific director of the IAVI NAC and the National Institutes of Health (NIH) Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID); and Ian Wilson, Hansen Professor of Structural Biology and chair of the Department of Integrative Structural and Computational Biology at TSRI.

    Developing a Blueprint

    A vaccine needs to elicit those rare antibodies, called “broadly neutralizing antibodies” (bnAbs), which fight a wide variety of strains of HIV—and it needs to elicit them quickly.

    One strategy to accomplish this, which scientists at TSRI have dubbed the “reductionist” strategy, is to find which antibody mutations are most important for making them effective against HIV, then to “prime” the immune system to start making antibody precursors. From there, scientists hope to prompt one important mutation after another with a series of different “booster” shots, deliberately building up a bnAb one step at a time.

    In a recent study in the journal PLOS Pathogens, the scientists created 3D maps of a structure on HIV known as the CD4 binding site. If antibodies successfully attack this site, scientists believe, most strains of HIV could be crippled. The researchers also created high-resolution maps of bnAbs that could bind to the CD4 binding site.

    “This is one of the most complete blueprints we’ve had for this target,” said Jean-Philippe Julien, a research associate in Wilson’s lab at the time of the study, who served as co-first author of the study with TSRI Research Associate Joseph Jardine, IAVI Research Scientist Devin Sok and Bryan Briney, assistant professor of immunology at TSRI.

    The scientists then studied stripped-down versions of the bnAbs to see exactly which components were important in targeting the CD4 binding site.

    With the results from the PLOS Pathogens study, the researchers finally had a guide to which mutations were the most important. They also had a better idea of which antibody-eliciting molecules, called immunogens, could be given in booster shots to trigger the right mutations at the right time.

    “We’re figuring how to boost antibodies to the next step—how to keep walking them along the path to increased breadth and potency after we get them started with a priming shot,” said Jardine.

    Training Promising Antibodies

    This finding set the stage for the three new studies. For the first one, published in Cell, researchers tested a priming immunogen, followed by a series of booster immunogens from the Schief lab. The immunogens were tested in a mouse model, developed by the Nemazee lab, which was engineered to have the genes (the raw materials) to make antibodies with the right mutations to target the CD4 binding site.

    The team found that the elicited antibodies more closely resembled mature antibodies. The sequence of immunogens had done their job.

    “The study showed that the immunogens are working,” said Nemazee. “They mutate the antibody-producing B cells in the right direction.”

    “The elicited antibodies share many genetic features with mature bnAbs and have the ability to neutralize one native HIV isolate as well as multiple other HIV isolates that we modified slightly to make them easier to neutralize,” added Briney, who served as first author of the study with Sok, Jardine, IAVI and TSRI Staff Scientist Daniel Kulp and TSRI Research Assistant Patrick Skog. “We will probably need additional booster immunogens to elicit antibodies that can broadly neutralize native HIV isolates, but our results suggest we are on the right track.”

    In the second Cell study, led by John R. Mascola at the NIH’s National Institute of Allergy and Infectious Disease (NIAID) Vaccine Research Center and Frederick W. Alt, a Howard Hughes Medical Institute (HHMI) researcher at Boston Children’s Hospital and Harvard Medical School, along with TSRI co-authors, took the reductionist approach a step further, showing that it could induce antibodies in mouse models with immune systems that can create an even wider range of antibodies—more similar to the human immune system.

    Results from the Science study further supported the reductionist vaccine approach. For the study, the researchers took on an even bigger challenge—to “prime” antibodies in a mouse model with a human-like immune system developed by Kymab Ltd, a UK-based company.

    The Kymab mouse model’s more complicated immune system made it more difficult for a vaccine protein to find and activate the “precursor” cells that have potential to produce bnAbs against the CD4 binding site. In fact, the researchers estimated that each Kymab mouse contained only one such precursor cell on average—with some mice containing none—among approximately 75 million antibody-producing cells.

    Despite this “needle-in-a-haystack” challenge, scientists found that their vaccine priming protein activated the appropriate antibody precursors in one-third to one-half of mice tested, suggesting this feat would also be possible in humans, where the targeted precursor cells are more plentiful. “This seems to be a much higher bar than we will face in humans,” Schief said.

    “The reductionist vaccine approach we’re undertaking will hopefully not only lead to an HIV vaccine, but also could potentially be applied to other challenging vaccine targets,” said Sok, who served as co-first author of the Science study with Briney, Jardine and Kulp.

    The researchers also gave credit to their strong international collaboration. “Our phenomenal results with the team at The Scripps Research Institute came from work at the interfaces—and boundaries—of vaccine technology, immunology, protein engineering and structural biology,” said Professor Allan Bradley, chief technical officer at Kymab and director emeritus of the Wellcome Trust Sanger Institute.

    IAVI and partners are planning for a clinical trial for next year to further develop and test whether the reductionist vaccine strategy—starting with activating the right precursors—will work in humans. If successful, the next step will be to test their booster immunogens.

    The first Cell study, Tailored Immunogens Direct Affinity Maturation Toward HIV Neutralizing Antibodies, included additional authors from the Ragon Institute. The study was supported by the IAVI through the NAC (grant SFP1849); NIAID grants; CHAVI-ID (grants UM1AI100663, P01AI081625 and R01AI073148); the Ragon Institute; and the Helen Hay Whitney Foundation.

    The second Cell study, Induction of HIV Neutralizing Antibody Lineages in Mice with Diverse Precursor Repertoires, included additional authors from HHMI; Boston Children’s Hospital; Harvard Medical School; the NIH’s NIAID Vaccine Research Center; Vanderbilt University; Columbia University; the Ragon Institute; Fred Hutchinson Cancer Center and the Duke University School of Medicine. This work was supported by the NIH (grants R01AI077595, AI020047, P01 AI094419, U19AI109632, P01-AI104722; CHAVI-ID (grants 5UM1 AI100645 and 1UM1 AI100663); the intramural research program of the NIAID Vaccine Research Center; the IAVI NAC Center; Collaboration for AIDS Vaccine Discovery funding for the IAVI NAC Center; the Ragon Institute and an HHMI Medical Student Fellowship.

    The Science study, Priming HIV-1 Broadly Neutralizing Antibody Precursors in Human Ig Loci Transgenic Mice, included additional authors from Kymab Ltd, the Wellcome Trust Sanger Institute and the Ragon Institute. The study was supported by IAVI, with the generous support of the United States Agency for International Development (USAID); Ministry of Foreign Affairs of the Netherlands; the Bill & Melinda Gates Foundation; the Ragon Institute; the Helen Hay Whitney Foundation; and NIAID (grants P01 AI094419 and CHAVI-ID 1UM1AI100663).

    See also additional Cell and Immunity studies on HIV/AIDS vaccine work led by TSRI scientists and published on September 8.

    See the full article here .

    YOU CAN HELP IN THE FIGHT AGAINST HIV/AIDS FROM THE COMFORT OF YOUR EASY CHAIR.

    The Fight AIDS at home (FAAH@home) Phase II project is now running at World Community Grid (WCG)

    FAAH Phase II

    WCG runs on your home computer or tablet on software from Berkeley Open Infrastructure for Network Computing [BOINC]. Many other scientific projects run on BOINC software.Visit WCG or BOINC, download and install the software, then at WCG attach to the FAAH@home Phase II project. You will be joining tens of thousands of other “crunchers” processing computational data and saving the scientists literally thousands of hours of work at no real cost to you.

    WCGLarge
    WCG Logo New

    BOINCLarge
    BOINC WallPaper

    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 11:03 am on August 23, 2016 Permalink | Reply
    Tags: , , , Scripps Institute   

    From Scripps: “A Look Deep Inside the Human Brain Reveals a Surprise” 

    Scripps
    Scripps Research Institute

    8.23.16
    No writer credit

    In the field of neuroscience, researchers often make the assumption that information they obtain from a tiny brain sample is true for the entire brain.

    Now, a team of scientists at The Scripps Research Institute (TSRI), University of California, San Diego (UC San Diego) and Illumina, Inc., has completed the first large-scale assessment of the way thousands of single neuronal nuclei produce proteins from genetic information (“transcription”) – revealing a surprising diversity in the process. The findings could improve both our understanding of the brain’s normal functioning and how it’s damaged by diseases such as Alzheimer’s, Parkinson’s, ALS and depression.

    [The study is published in Science.]

    The researchers accomplished this feat by isolating and analyzing 3,200 single human neurons, more than 10-fold greater than prior publications, from six Brodmann Areas (larger regions having functional roles) of the human brain.

    “Through a wonderful scientific collaboration, we found an enormous amount of transcriptomic diversity from cell to cell that will be relevant to understanding the normal brain and its diseases such as Alzheimer’s, Parkinson’s, ALS and depression,” said TSRI Professor and neuroscientist Jerold Chun, who co-led the study with bioengineers Kun Zhang and Wei Wang of UC San Diego and Jian-Bing Fan of Illumina.

    While parts of the cerebral cortex look different under a microscope – with different cell shapes and densities that form cortical layers and larger regions having functional roles called “Brodmann Areas” – most researchers treat neurons as a fairly uniform group in their studies. “From a tiny brain sample, researchers often make assumptions that obtained information is true for the entire brain,” said Dr. Chun.

    But the brain isn’t like other organs, Dr. Chun explained. There’s a growing understanding that individual brain cells are unique, and a possibility has been that the microscopic differences among cerebral cortical areas may also reflect unique transcriptomic differences – i.e., differences in the expressed genes, or messenger RNAs (mRNAs), which carry copies of the DNA code outside the nucleus and determine which proteins the cell makes.

    With the help of newly developed tools to isolate and sequence individual cell nuclei (where genetic material is housed in a cell), the researchers deciphered the minute quantities of mRNA within each nucleus, revealing that various combinations of the 16 subtypes tended to cluster in cortical layers and Brodmann Areas, helping explain why these regions look and function differently.

    Neurons exhibited anticipated similarities, yet also many differences in their transcriptomic profiles, revealing single neurons with shared, as well as unique, characteristics that likely lead to differences in cellular function.

    “Now we can actually point to an enormous amount of molecular heterogeneity in single neurons of the brain,” said Gwendolyn E. Kaeser, a UC San Diego Biomedical Sciences Graduate Program student studying in Dr. Chun’s lab at TSRI and co-first author of the study.

    Interestingly, some of these differences in gene expression have roots in very early brain development taking place before birth. The researchers found markers on some neurons showing that they originated from a specific region of fetal brain called the ganglionic eminence, which generates inhibitory neurons destined for the cerebral cortex. These neurons may have particular relevance to developmental brain disorders.

    In future studies, the researchers hope to investigate how single-neuron DNA and mRNA differ in single neurons, groups and between human brains – and how these may be influenced by factors such as stress, medications or disease.

    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 12:21 pm on August 18, 2016 Permalink | Reply
    Tags: , , Scripps Institute, TSRI Scientists Find Potential Treatment for 'Painful Blindness' Form of Dry Eye   

    From Scripps: “TSRI Scientists Find Potential Treatment for ‘Painful Blindness’ Form of Dry Eye” 

    Scripps
    Scripps Research Institute

    August 18, 2016
    No writer credit

    1
    The Scripps Research Institute team found “progenitor” cells isolated from healthy lacrimal glands can improve the appearance and function of diseased tissue. (Image courtesy of TSRI’s Makarenkova lab.)

    The eye’s lacrimal gland is small but mighty. This gland produces moisture needed to heal eye injuries and clear out harmful dust, bacteria and other invaders.

    If the lacrimal gland is injured or damaged by aging, pollution or even certain pharmaceutical drugs, a person can experience a debilitating condition called aqueous deficiency dry eye (ADDE)—sometimes called “painful blindness.”

    Now a new study in animal models, led by scientists at The Scripps Research Institute (TSRI), suggests that lacrimal glands can be repaired by injecting a kind of regenerative “progenitor” cell.

    “This is the first step in developing future therapies for the lacrimal gland,” said TSRI biologist Helen Makarenkova, who led the study.

    The findings were published this week in the online Early Edition of the journal Stem Cells Translational Medicine.

    Up for the Challenge

    If injured, a healthy lacrimal gland naturally regenerates itself in about seven days. When diseased and chronically inflamed, however, regeneration stops—and scientists are not sure why.

    In the new study, Makarenkova and her colleagues looked at whether they could kick start regeneration by injecting progenitor cells into the lobes that make up the lacrimal gland. Progenitor cells are similar to stem cells in their ability to differentiate into different kinds of tissue. In this study, the researchers used progenitor cells that were poised to become epithelial tissue, a key component of the lacrimal gland.

    The researchers knew they faced a major challenge: sorting and separating “sticky” epithelial cell progenitors without destroying them.

    “We had to figure out how to dissociate the tissue into single cells without completely obliterating everything,” said Anastasia Gromova, the study’s first author, now a graduate student at the University of California, San Diego, who spearheaded the project while interning at TSRI during her undergraduate years.

    The researchers solved this problem by developing markers to label the cells of interest and then testing different enzymes and other reagents to draw them out of tissues.

    Restoring Eye Health

    With these cells in hand, the researchers injected them into the lacrimal glands of mouse models of Sjogren’s syndrome, an autoimmune disease that results in ADDE, dry mouth and other symptoms. The team used only older, female mice because ADDE most commonly strikes that demographic in humans.

    The treated mice showed a significant increase in tear production, indicating—for the first time—that epithelial cell progenitors could repair the lacrimal gland. Further tests suggested that epithelial cell progenitors helped by restoring the connection between cells called myoepithelial contractile cells and the lacrimal gland’s secretory cells, which produce tears.

    The next step in this research will be to study how long the improvement in the lacrimal gland lasts after progenitor cell injections. Makarenkova said the eventual goal is to develop therapies to boost a patient’s own regenerative abilities.

    In addition to Makarenkova and Gromova, authors of the study, “Lacrimal Gland Repair Using Progenitor Cells,” were Dmitry A. Voronov of TSRI, the Russian Academy of Sciences and the A.N. Belozersky Institute of Physico-Chemical Biology of the Lomonosov Moscow State University; Miya Yoshida and Suharika Thotakura of TSRI; Robyn Meech of Flinders University; and Darlene A. Dartt of the Schepens Eye Research Institute/Massachusetts Eye and Ear, Harvard Medical School.

    The research was supported by the National Institutes of Health’s National Eye Institute (grant EY021292), the Russian Foundation for Basic Research (grant 12-04-01621-a) and an Australian Research Council (ARC) Future 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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