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  • richardmitnick 5:02 pm on December 14, 2017 Permalink | Reply
    Tags: Amino acids are the building blocks of proteins, , Est1 is a subunit of a protein (an enzyme) called telomerase, , Identifing previously undiscovered activities for a protein, , Protein Studies,   

    From Salk: “Revealing the best-kept secrets of proteins” 

    Salk Institute bloc

    Salk Institute for Biological Studies

    December 14, 2017
    No writer credit

    1
    From left: John Lubin, Vicki Lundblad and Tim Tucey. Credit: Salk Institute

    Salk scientists develop new approach to identify important undiscovered functions of proteins.

    In the bustling setting of the cell, proteins encounter each other by the thousands. Despite the hubbub, each one manages to selectively interact with just the right partners, thanks to specific contact regions on its surface that are still far more mysterious than might be expected, given decades of research into protein structure and function.

    Now, Salk Institute scientists have developed a new method to discover which surface contacts on proteins are critical for these cellular interactions. The novel approach shows that essential new functions can be uncovered even for well-studied proteins, and has significant implications for therapeutic drug development, which depends heavily on how drugs physically interact with their cellular targets. The paper appeared in the early online version of Genetics in late November, and is slated for publication in the January print edition of the journal.

    “This paper illustrates the power of this methodology,” says senior author Vicki Lundblad, holder of the Ralph S. and Becky O’Conner Chair. “It can not only identify previously undiscovered activities for a protein, but it can also pinpoint the exact amino acids on a protein surface that perform these new functions.”

    Amino acids are the building blocks of proteins. Their specific linear arrangement determines the identity of a protein, and clusters of them on the protein’s surface serve as contacts, regulating how that protein interacts with other proteins and molecules. Lundblad and her colleagues suspected that, despite decades of work deciphering the mysteries of proteins, the extent of this regulatory landscape on the surface of proteins had remained mostly unexplored. Long ago, her group unexpectedly discovered one such regulatory amino acid cluster, while searching one-by-one through 300,000 mutant yeast cells. Although that work opened up a new area of research in the field of telomere biology, Lundblad was determined to figure out a more robust methodology that could rapidly uncover many more of these unexplored protein surfaces.

    Enter John Lubin, now a PhD student in Lundblad’s lab, who began working with her as an undergraduate.

    “My task was to figure out how to search through 30 mutant yeast cells, instead of 300,000, to discover new activities for a protein,” says Lubin, the paper’s co–first author. Timothy Tucey, the other co–first author, was a postdoctoral researcher in Lundblad’s group and is now at Monash University.

    Together they turned to a protein called Est1, which Lundblad had discovered in yeast as a postdoctoral researcher in 1989. Est1 is a subunit of a protein (an enzyme) called telomerase, which keeps the protective caps at the ends of chromosomes (known as telomeres) from getting too short. As the first subunit of telomerase to be discovered, Est1 has been subjected to intensive study by many research groups.

    The Salk team’s approach involved introducing a small, but customized, set of mutations into yeast cells that would selectively disrupt surface contacts on the cells’ Est1 protein. The team then analyzed the cells to see what effect, if any, the various mutations had. Abnormalities resulting from a specific mutation would suggest what the role of the unmutated version was. To do so, they used a genetic trick, by flooding the cells with each mutant protein, and looking for the rare mutant protein that could interfere with cell function, as their previous work had shown that this would preferentially target the protein surface.

    Lundblad’s team discovered four functions for Est1 through this approach. Impairment of any of these four functions by mutations to Est1’s surface amino acids, the scientists found, resulted in cells that had critically short telomeres, indicating specific roles for the Est1 contacts in the telomerase complex.

    “What has us excited about this technique is that it can be applied to numerous proteins,” says Lundblad. “In particular, many therapeutic drugs rely on being able to access a very specific location on a protein surface, which we suspect can be uncovered by this method.”

    Using this approach, her team has already uncovered new functions for a set of proteins that regulate the stability of the genome, and has also applied for grants that fund research into drug targets.

    The work was funded by the National Institutes of Health, the National Science Foundation, the Rose Hills Foundation and the Glenn Center for Aging Research.

    See the full article here .

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    Salk Institute Campus

    Every cure has a starting point. Like Dr. Jonas Salk when he conquered polio, Salk scientists are dedicated to innovative biological research. Exploring the molecular basis of diseases makes curing them more likely. In an outstanding and unique environment we gather the foremost scientific minds in the world and give them the freedom to work collaboratively and think creatively. For over 50 years this wide-ranging scientific inquiry has yielded life-changing discoveries impacting human health. We are home to Nobel Laureates and members of the National Academy of Sciences who train and mentor the next generation of international scientists. We lead biological research. We prize discovery. Salk is where cures begin.

     
  • richardmitnick 5:59 pm on December 10, 2017 Permalink | Reply
    Tags: , , , Neuronal networks, , Peter Jonas, Protein Studies, Synaptotagmin 7, Synaptotagmin proteins   

    From IST Austria “Researchers at IST Austria define function of an enigmatic synaptic protein” 

    IST Austria

    November 21, 2017

    Synaptotagmin 7 ensures efficiency of inhibitory signal transmission – Study published in Cell Reports

    1
    Photo credit: Chen et al, Cell Reports

    Communication is often mired in contradiction – also in the brain. Neuroscientists at IST Austria were now able to resolve one such contradiction.

    In our brains, neurons communicate by sending chemical signals across their connections, the synapses. The molecular machinery required to send a signal involves not only the signal itself, the neurotransmitter, but a large variety of other proteins that act as sensors, effectors, modulators, and scaffolds. Synaptotagmins are part of this complex machinery. Synaptotagmin proteins come in many flavours: humans and other mammals have 17 different varieties. For most of these proteins, however, scientists do not yet understand the function. A group of neuroscientists led by Peter Jonas, Professor at the Institute of Science and Technology Austria (IST Austria), have now resolved the role of Synaptotagmin 7 during signal transmission at an inhibitory synapse. Writing in Cell Reports, the team, including first author and PhD student Chong Chen as well as researchers at the Max Planck Florida Institute for Neuroscience, shows that Synaptotagmin 7 ensures the efficiency of high-frequency inhibitory synaptic transmission. “The role of Synaptotagmin 7 has been controversial. For the first time, we defined its functional contribution at an inhibitory GABAergic synapse”, explains lead author Peter Jonas.

    Conflicting role in signal transmission

    Only in January of this year, Jonas and Chen showed that Synaptotagmin 2 is the calcium sensor that makes certain synapses fast – those that use the transmitter GABA. In the current study, the researchers turned their attention to another member of the Synaptotagmin family, Synaptotagmin 7. The brain contains a large amount of Synaptotagmin 7, but so far, scientists were not able to pinpoint the protein’s function. Partly, the reason is a contradiction between the function Synaptotagmin 7 seemed to have, and the characteristics of signal transmission observed.

    Synaptotagmin 7 appears to function as a calcium sensor that mediates the release of a variable barrage of neurotransmitter into the synaptic cleft, a phenomenon called asynchronous transmitter release. There are also indications that Synaptotagmin 7 plays a role in facilitation, an increase in neurotransmission at the synapse. But on the other hand Synaptotagmin 7 is also found in large amounts in a class of neurons called fast-spiking, parvalbumin-expressing GABAergic interneurons. These neurons form synapses which appear to contradict the suggested functions of Synaptotagmin 7: the synapses release neurotransmitter in a tightly synchronized manner, rather than asynchronously, and show a reduction in neurotransmission, rather than facilitation during repetitive stimulation. In their study, Chen et al. now resolve this apparent contradiction.

    Synaptotagmin 7 regulates information flow in cerebellum

    The researchers investigated how signal transmission changes when they delete Synaptotagmin 7 in an inhibitory synapse, the GABAergic synapse between the basket cells (BCs) and Purkinje cells (PCs) in the cerebellum (a brain region required for motor control). They show that, indeed, the function of Synaptotagmin 7 is to contribute to asynchronous transmitter release, replenishment of vesicles containing neurotransmitter, and facilitation. But rather than being mutually exclusive, these three functions appear to coexist at BC-PC synapses. Elucidating the effects of Synaptotagmin 7 required careful analysis, because asynchronous release is small and facilitation is overlaid by depression. However the authors demonstrate a substantial difference in the extent of depression. Little depression occurred in the presence of Synaptotagmin 7, but a lot of depression was found in the absence of Synaptotagmin 7. Thus, Synaptotagmin 7 ensures the efficient and frequency-independent signal transmission at the BC-PC synapse, one of its fundamental properties.

    When the researchers looked at the level of neuronal networks, they found that Synaptotagmin 7 allows single basket cells to control the activity of a Purkinje cell. These neurons are the only ones that send information out of the cerebellum. Synaptotagmin 7 therefore has a strategic position to regulate the flow of information in this motor circuit. The researchers also found that Synaptotagmin 7 plays a similar (albeit quantitatively smaller) role at BC synapses in the hippocampus, a seahorse-shaped brain region involved in memory and spatial coding. Peter Jonas summarizes: “We have identified a critical role for Synaptotagmin 7 in maintaining the efficacy of transmission at GABAergic synapses in the cerebellum and hippocampus.”

    See the full article here.

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    The Institute of Science and Technology Austria (IST Austria) is a young international institute dedicated to basic research and graduate education in the natural and mathematical sciences, located in Klosterneuburg on the outskirts of Vienna. Established jointly by the federal government of Austria and the provincial government of Lower Austria, the Institute was inaugurated in 2009 and will grow to about 90 research groups by 2026.

    The governance and management structures of IST Austria guarantee its independence and freedom from political and commercial influences. The Institute is headed by the President, who is appointed by the Board of Trustees and advised by the Scientific Board. The first President of IST Austria is Thomas A. Henzinger, a leading computer scientist and former professor of the University of California at Berkeley and the EPFL Lausanne in Switzerland.

     
  • richardmitnick 10:37 am on November 29, 2017 Permalink | Reply
    Tags: , , Dnm1 proteins, , Protein Studies, , , UCLA bioengineers discover mechanism that regulates cells’ ‘powerhouses’   

    From UCLA Newsroom: “UCLA bioengineers discover mechanism that regulates cells’ ‘powerhouses’” 


    UCLA Newsroom

    November 27, 2017
    Matthew Chin

    1
    In this artist’s rendering, Dnm1 proteins surrounding a mitochondrion are breaking it up into two. Jaime de Anda/ACS Central Science.

    UCLA bioengineers and their colleagues have discovered a new perspective on how cells regulate the sizes of mitochondria, the parts of cells that provide energy, by cutting them into smaller units.

    The researchers wrote that this finding, demonstrated with yeast proteins, could eventually be used to help address human diseases associated with an imbalanced regulation of mitochondria size — for example, Alzheimer’s or Parkinson’s diseases. In addition, since having mitochondria that are too small or too large can potentially lead to incurable diseases, it is conceivable that the proteins responsible for this process could be potential targets for future therapies.

    The study was published in ACS Central Science and was led by UCLA bioengineering professor Gerard Wong.

    Inside the cell, mitochondria resemble the long balloons used to create balloon animals. If the mitochondria are too long, they can get tangled. Their sizes are known to be primarily regulated by two proteins, one of which breaks up longer mitochondria into smaller sizes. They are known as cells’ “powerhouses” as they convert chemical energy from food into a form useful for cells to perform all their functions.

    Keeping mitochondria at optimal sizes is important to cells’ health. An insufficient amount of the regulating protein, known as Dnm1, results in the mitochondria getting too long and tangled. Too much Dnm1 results in too many short mitochondria. In both cases, the mitochondria are rendered essentially ineffective as power providers for the cell. This situation could lead to neurodevelopmental disorders or neurodegenerative diseases, such as Alzheimer’s or Parkinson’s.

    To better understand this mechanism, the researchers used a machine-learning approach they developed in 2016 to figure out exactly how the proteins break up one mitrochondrion into two smaller ones. They also used a powerful technique called “synchrotron small-angle X-ray scattering” at the Stanford Synchrotron Radiation Lightsource, a U.S. Department of Energy research facility, to see how these proteins deform mitochondrial membranes during this process.

    SLAC/SSRL

    Before this study, it was thought that these proteins encircled the mitochondria, then cut it in two by simply squeezing tightly. The process, the team discovered, is more subtle.

    “When Dnm1 wraps around mitochondria, it has been previously shown that the protein physically tightens and pinches,” said Michelle Lee, a recent UCLA bioengineering doctoral graduate who was advised by Wong and is one of two lead authors of the study. “What we found is that when Dnm1 contacts the mitochondrial surface, it also makes that area of the mitochondrion itself more moldable and easier to undergo cleavage. These two effects work hand in hand to make the process of mitochondrial division efficient.”

    The other lead author is Ernest Lee, a graduate student in the UCLA-Caltech Medical Scientist Training Program and a bioengineering graduate student also advised by Wong. He carried out the computational analyses for the experiment.

    “Using our machine-learning tool, we were able to discover hidden membrane-remodeling activity in Dnm1, consistent with our X-ray studies,” Lee said. “Interestingly, by analyzing distant relatives of Dnm1, we found that the protein gradually evolved this ability over time.”

    “This is a very unexpected result — no one thought these molecules would have a split personality, with both personalities necessary for the biological function,” said Wong, who is also a UCLA professor of chemistry and biochemistry and is a member of the California NanoSystems Institute. “The multifunctional behavior we identified may be the rule rather than the exception for proteins.”

    Other authors include Andy Ferguson from the University of Illinois at Urbana-Champaign and Blake Hill from the Medical College of Wisconsin.

    The research was supported by the National Science Foundation and the National Institutes of Health, with additional support from the Department of Energy for imaging experiments.

    See the full article here .

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    For nearly 100 years, UCLA has been a pioneer, persevering through impossibility, turning the futile into the attainable.

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  • richardmitnick 9:51 am on October 2, 2017 Permalink | Reply
    Tags: , , , Protein Studies, ,   

    From U Washington Medicine: “Mini-protein rapid design opens way to new class of drugs” 

    U Washington

    University of Washington

    September 27, 2017
    Leila Gray
    206.685.0381
    leilag@uw.edu

    Scientists at the Institute for Protein Design have created a way to generate thousands of different mini-protein binders as possible drug candidates. The proteins can be custom tailored to specific therapeutic targets. Recently, a set of these proteins were successfully tested in mice against the flu, and another group of these binders was able to protect brain cells against the botulism neurotoxin.

    1
    Artist impression of designed mini-protein binders targeting Influenza hemagglutinin to effectively bind and neutralize the virus. Cognition Studio, Daniel-Adriano Silva, Lance Stewart

    These computer-designed proteins, which did not previously exist in nature, combine the stability and bioavailability of small molecule drugs with the specificity and potency of larger biologics. They would not require refrigeration, and they likely would be simple for patients to take.

    “These mini-protein binders have the potential of becoming a new class of drugs that bridge the gap between small molecule drugs and biologics. Like monoclonal antibodies, they can be designed to bind to targets with high selectivity, but they are more stable and easier to produce and to administer,” said David Baker, who led the multi-institutional research project. He is a professor of biochemistry at the University of Washington School of Medicine and director of the UW Institute for Protein Design.

    Dr. David Baker, Baker Lab, U Washington

    Baker and his colleagues report their findings in article published online Sept. 27 by the journal Nature.

    Aaron Chevalier, Daniel-Adriano Silva and Gabriel J. Rocklin were the lead authors and were all senior fellows at the UW Institute for Protein Design at the time of the project.

    The method used a computer platform, called Rosetta, developed by Baker and colleagues at the University of Washington. They designed thousands of short proteins, about 40 amino acids in length, that the Rosetta program predicted would bind tightly to the molecular target.

    Rosetta@home project, a project running on BOINC software from UC Berkeley


    Rosetta@home BOINC project

    BOINC

    My BOINC

    Because of their small size, these short proteins tend to be extremely stable. They can be stored without refrigeration. They also are more easily administered than large protein drugs, such as monoclonal antibodies.

    Previously, such short, protein-binder drugs were typically re-engineered versions of naturally occurring proteins. These, however, tended not to be significantly better than monoclonal antibodies.

    Because these mini-proteins binders are original designs, they can be tailored to fit their targets much more tightly and are simpler to modify and refine.

    In this study, the researchers sought to design two sets of these proteins: one set that would prevent the influenza virus from invading cells and another that would bind to and neutralize a deadly nerve toxin from botulism. This toxin is considered a potential bioweapon.

    The computer modeling identified the amino-acid sequences of thousands of short proteins that would fit into and bind to the influenza and botulinum targets. The researchers created short pieces of DNA that coded each of these proteins, grew the proteins in yeast cells, and then looked at how tightly they bound to their targets. The targets were Influenza H1 hemagglutinin and botulinum neurotoxin B.

    All told, the method allowed them to design and test 22,660 proteins in just a few months. More than than two-thousand of them bound to their targets with high affinity.

    Evaluation of the best candidates found that the anti-influenza proteins neutralized viruses in cell culture and other designed proteins prevented the botulinum toxin from entering brain cells.

    A nasal spray containing one of the custom-designed proteins completely protected mice from the flu if administered before or as much as 72 hours after exposure.. The protection that the treatment provides equaled or surpassed that seen with antibodies, the researchers report.

    Testing of a subset of the proteins showed that they were extremely stable and, unlike antibodies, did not become inactivated by high temperatures. The small proteins also triggered little or no immune response, a problem that often renders larger protein drugs ineffective.

    Funding for the study came from Life Sciences Discovery Fund Launch grant (9598385), Doctorado en Ciencias Bioquiacutemicas UNAM (R56AI117675), Molecular Basis of Viral Pathogenesis Training Grant (T32AI007354-26A1), Investigator in the Pathogenesis of Infectious Disease award from the Burroughs Wellcome Fund and NIH (1R01NS080833), CoMotion Mary Gates Innovation Fellow; Shenzhen Science and Technology Innovation Committee (JCYJ20170413173837121), Hong Kong Research Grant Council (C6009-15G and AoE/P-705/16), PAPIIT UNAM (IN220516), CONACyT (254514) and Facultad de Medicina UNAM (AI091823, AI123920,AI125704), NIAID grant (1R41AI122431) (1R21AI119258), and Life Sciences Discovery Fund grant (20040757).

    See the full article here .

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  • richardmitnick 12:13 pm on August 31, 2017 Permalink | Reply
    Tags: , , Progeria, Protein Studies, Protein turnover could be clue to living longer,   

    From Salk: “Protein turnover could be clue to living longer” 

    Salk Institute bloc

    Salk Institute for Biological Studies

    August 30, 2017

    Overactive protein synthesis found in premature aging disease may also play role in normal aging.

    Scientists at the Salk Institute found that protein synthesis is overactive in people with progeria. The work, described in Nature Communications on August 30, 2017, adds to a growing body of evidence that reducing protein synthesis can extend lifespan—and thus may offer a useful therapeutic target to counter both premature and normal aging.

    “The production of proteins is an extremely energy-intensive process for cells,” says Martin Hetzer, vice president and chief science officer of the Salk Institute and senior author of the paper. “When a cell devotes valuable resources to producing protein, other important functions may be neglected. Our work suggests that one driver of both abnormal and normal aging could be accelerated protein turnover.”

    2
    Nucleoli in the cell nucleus, stained bright magenta and cyan against the purple backdrop of the nucleus, are enlarged in the progeria cell (right) compared to the normal cell (left). Credit: Salk Institute

    Hutchinson-Gilford progeria is a very rare genetic disease causing people to age 8 to 10 times faster than the rest of us and leading to an early death. The rare mutation occurs in one of the structural proteins in the cell nucleus, lamin A, but it has been unclear how a single defective protein in the nucleus causes the myriad rapid-aging features seen in the disease.

    Initially, Salk Staff Scientist Abigail Buchwalter, first author of the paper, was interested in whether the mutation was making the lamin A protein less stable and shorter lived. After measuring protein turnover in cultured cells from skin biopsies of both progeria sufferers and healthy people, she found that it wasn’t just lamin A that was affected in the disease.

    “We analyzed all the proteins of the nucleus and instead of seeing rapid turnover in just mutant lamin A and maybe a few proteins associated with it, we saw a really broad shift in overall protein stability in the progeria cells,” says Buchwalter. “This indicated a change in protein metabolism that we hadn’t expected.”

    Along with the rapid turnover of proteins, the team found that the nucleolus, which makes protein-assembling structures called ribosomes, was enlarged in the prematurely aging cells compared to healthy cells.

    Even more intriguing, the team found that nucleolus size increased with age in the healthy cells, suggesting that the size of the nucleolus could not only be a useful biomarker of aging, but potentially a target of therapies to counter both premature and normal aging.

    The work supports other research that appears in the same issue showing that decreasing protein synthesis extends lifespan in roundworms and mice. The Hetzer lab plans to continue studying how nucleolus size may serve as a reliable biomarker for aging.

    “We always assume that aging is a linear process, but we don’t know that for sure,” says Hetzer, who also holds the Jesse and Caryl Philips Foundation Chair. “A biomarker such as this that tracks aging would be very useful, and could open up new ways of studying and understanding aging in humans.”

    The work was funded by the National Institutes of Health, the Nomis Foundation, and the Glenn Center for Aging Research.

    See the full article here .

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    Salk Institute Campus

    Every cure has a starting point. Like Dr. Jonas Salk when he conquered polio, Salk scientists are dedicated to innovative biological research. Exploring the molecular basis of diseases makes curing them more likely. In an outstanding and unique environment we gather the foremost scientific minds in the world and give them the freedom to work collaboratively and think creatively. For over 50 years this wide-ranging scientific inquiry has yielded life-changing discoveries impacting human health. We are home to Nobel Laureates and members of the National Academy of Sciences who train and mentor the next generation of international scientists. We lead biological research. We prize discovery. Salk is where cures begin.

     
  • richardmitnick 6:35 am on July 21, 2017 Permalink | Reply
    Tags: , , Protein Studies,   

    From Salk: “New method to rapidly map the “social networks” of proteins” 

    Salk Institute bloc

    Salk Institute for Biological Studies

    June 26, 2017
    Office of Communications
    Tel: (858) 453-4100
    press@salk.edu

    Salk scientists improved upon a classic approach to mapping the interactions between proteins.

    1
    A new mapping method let researchers discover new links (gray lines) between two groups of plant proteins (yellow and blue) that have a common structure (the BBX domain), suggesting many different combinations of interactions, rather than a few, are involved in coordinating cellular programs like flowering time and circadian rhythm. Credit: Salk Institute.

    Salk scientists have developed a new high-throughput technique to determine which proteins in a cell interact with each other. Mapping this network of interactions, or “interactome,” has been slow going in the past because the number of interactions that could be tested at once was limited. The new approach, published June 26 in Nature Methods, lets researchers test millions of relationships between thousands of proteins in a single experiment.

    “The power of this new approach is in the ability we now have to scale it up,” says senior author Joseph Ecker, professor and director of Salk’s Genomic Analysis Laboratory and investigator of the Howard Hughes Medical Institute. “This assay has the potential to begin to address questions about fundamental biological interactions that we haven’t been able to address before.”

    The interactome of a cell, like a map of social networks, lets scientists see who’s working with who in the world of proteins. This helps them figure out the roles of different proteins and piece together the different players in molecular pathways and processes. If a newly discovered protein interacts with lots of other proteins involved in cellular metabolism, for instance, researchers can deduce that’s a likely role for the new protein and potentially target it for treatments related to metabolic dysfunction.

    Until now, researchers have typically relied on standard high-throughput yeast two-hybrid (Y2H) assays to determine the interactions between proteins. The system requires using a single known protein—known as the “bait”—to screen against a pool of “prey” proteins. But finding all the interactions between, for instance, 1,000 proteins, would require 1000 separate experiments to screen once for each bait’s interaction partners.

    “Current technologies essentially require that interactions detected in primary screening get retested individually,” says Shelly Trigg, an NSF Graduate Research Fellow at the University of California, San Diego, in the Ecker lab, and first author of the new paper. “That may no longer be necessary with the screening depth this approach achieves.”

    In their new method, Ecker, Trigg and their colleagues added a twist to the standard Y2H assay for a much more effective way of measuring the interactome. The genes for two proteins, each on their own circle of DNA, are added to the same cell. If the proteins of interest interact inside the cell, a gene called Cre is activated. When turned on, Cre physically splices the two individual circles of DNA together, thus pairing the genes of interacting proteins together so the team can easily find them through sequencing. The team can generate a massive library of yeast cells—each containing different pairs of proteins by introducing random combinations of genes on circular DNA called plasmids. When cells are positive for a protein interaction, the researchers can use genetic sequencing to figure out what the two proteins interacting are, using new high-throughput DNA sequencing technologies similar to those used for human genome sequencing. This way, they’re no longer limited to testing one “bait” protein at a time, but could test the interactions between all the proteins in a library at once.

    2
    Joseph Ecker (courtesy of Salk Institute) and Shelly Trigg (courtesy of Austin Trigg)

    Ecker’s group tested the new method, dubbed CrY2H-seq, on all the transcription factors—a large class of proteins—in the plant Arabidopsis.

    “When you take 1,800 proteins and test the interactions among them, that’s nearly 4 million combinations,” says Ecker. “We did that ten times in a matter of a month.”

    They revealed more than 8,000 interactions among those proteins tested, giving them new insight into which Arabidopsis transcription factors interact with each other. The data, they say, helps answer longstanding questions about whether certain groups of transcription factors have set functions. Some of the poorly understood transcription factors, they found, interact with more well-understood factors that regulate the plant’s response to auxin, a hormone involved in coordinating plant growth.

    In the future, the method could be scaled up to test larger sets of proteins—human cells, for instance, contain about 20,000 different proteins. This easier and faster method to determine the entire interactome of a cell also opens up the possibility of studying how the interactome changes under different conditions—an experiment that’s never been possible in the past.

    Other researchers on the study were Renee Garza, Andrew MacWilliams, Joseph Nery, Anna Bartlett, Rosa Castanon, Adeline Goubil, Joseph Feeney, Ronan O’Malley, Shao-shan Carol Huang, Zhuzhu Zhang, and Mary Galli of the Salk Institute.

    See the full article here .

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    Salk Institute Campus

    Every cure has a starting point. Like Dr. Jonas Salk when he conquered polio, Salk scientists are dedicated to innovative biological research. Exploring the molecular basis of diseases makes curing them more likely. In an outstanding and unique environment we gather the foremost scientific minds in the world and give them the freedom to work collaboratively and think creatively. For over 50 years this wide-ranging scientific inquiry has yielded life-changing discoveries impacting human health. We are home to Nobel Laureates and members of the National Academy of Sciences who train and mentor the next generation of international scientists. We lead biological research. We prize discovery. Salk is where cures begin.

     
  • richardmitnick 11:12 am on July 17, 2017 Permalink | Reply
    Tags: , Protein Studies, , Synthetic DNA technology and high throughput screening permit large-scale testing of structural stability of multitudes of computationally designed proteins,   

    From U Washington: “Feedback from 1000s of designs could transform protein engineering” 

    U Washington

    University of Washington

    07.12.2017
    Leila Gray
    206.685.0381
    leilag@uw.edu

    1
    A model of a computationally designed mini-protein from a large-scale study to test structural stability. Institute for Protein Design.

    The stage is set for a new era of data-driven protein molecular engineering as advances in DNA synthesis technology merge with improvements in computational design of new proteins.

    This week’s Science reports the largest-scale testing of folding stability for computationally designed proteins, made possible by a new high-throughput approach.

    The scientists are from the UW Medicine Institute for Protein Design at the University of Washington in Seattle and the University of Toronto in Ontario.

    The lead author of the paper is Gabriel Rocklin, a postdoctoral fellow in biochemistry at the University of Washington School of Medicine. The senior authors are Cheryl Arrowsmith, of the Princess Margaret Cancer Center, the Structural Genomics Consortium and the Department of Medical Biophysics at the University of Toronto, and David Baker, UW professor of biochemistry and a Howard Hughes Medical Institute investigator.

    Proteins are biological workhorses. Researchers want to build new molecules, not found naturally, that can perform tasks in preventing or treating disease, in industrial applications, in energy production, and in environmental cleanups.

    “However, computationally designed proteins often fail to form the folded structures that they were designed to have when they are actually tested in the lab,” Rocklin said.

    In the latest study, the researchers tested more than 15,000 newly designed mini-proteins that do not exist in nature to see whether they form folded structures. Even major protein design studies in the past few years have generally examined only 50 to 100 designs.

    “We learned a huge amount at this new scale, but the taste has given us an even larger appetite,” said Rocklin. “We’re eager to test hundreds of thousands of designs in the next few years.”

    The most recent testing led to the design of 2,788 stable protein structures and could have many bioengineering and synthetic biology applications. Their small size may be advantageous for treating diseases when the drug needs to reach the inside of a cell.

    2
    Design model structures from a comprehensive mutational analysis of stability in natural and designed proteins. UW Institute for Protein Design.

    Proteins are made of amino acid chains with specific sequences, and natural protein sequences are encoded in cellular DNA. These chains fold into 3-dimensional conformations. The sequence of the amino acids in the chain guide where it will bend and twist, and how parts will interact to hold the structure together.

    For decades, researchers have studied these interactions by examining the structures of naturally occurring proteins. However, natural protein structures are typically large and complex, with thousands of interactions that collectively hold the protein in its folded shape. Measuring the contribution of each interaction becomes very difficult.

    The scientists addressed this problem by computationally designing their own, much simpler proteins. These simpler proteins made it easier to analyze the different types of interactions that hold all proteins in their folded structures.

    “Still, even simple proteins are so complicated that it was important to study thousands of them to learn why they fold,” Rocklin said. “This had been impossible until recently, due to the cost of DNA. Each designed protein requires its own customized piece of DNA so that it can be made inside a cell. This has limited previous studies to testing only tens of designs.”

    To encode their designs of short proteins in this project, the researchers used what is called DNA oligo library synthesis technology. It was originally developed for other laboratory protocols, such as large gene assembly. One of the companies that provided their DNA is CustomArray in Bothell, Wash. They also used DNA libraries made by Agilent in Santa Clara, Calif., and Twist Bioscience in San Francisco.

    By repeating the cycle of computation and experimental testing over several iterations, the researchers learned from their design failures and progressively improved their modeling. Their design success rate rose from 6 percent to 47 percent. They also produced stable proteins in shapes where all of their first designs failed.

    Their large set of stable and unstable mini-proteins enabled them to quantitatively analyze which protein features correlated with folding. They also compared the stability of their designed proteins to similarly sized, naturally occurring proteins.

    The most stable natural protein the researchers identified was a much-studied protein from the bacteria Bacillus stearothermophilus.

    3
    The researchers compared the stability of some of their designed proteins to a natural protein found in a bacteria that withstands the high temperatures of hot springs like those in Yellowstone. Alice C. Gray.

    This organism basks in high temperatures, like those in hot springs and ocean thermal vents. Most proteins lose their folded structures under such high temperature conditions. Organisms that thrive there have evolved highly stable proteins that stay folded even when hot.

    “A total of 774 designed proteins had higher stability scores than this most protease-resistant monomeric protein,” the researchers noted. Proteases are enzymes that break down proteins, and were essential tools the researchers used to measure stability for their thousands of proteins.

    The researchers predict that, as DNA synthesis technology continues to improve, high-throughput protein design will become possible for larger, more complex protein structures.

    “We are moving away from the old style of protein design, which was a mix of computer modeling, human intuition, and small bits of evidence about what worked before.” Rocklin said. “Protein designers were like master craftsmen who used their experience to hand-sculpt each piece in their workshop. Sometimes things worked, but when they failed it was hard to say why. Our new approach lets us collect an enormous amount of data on what makes proteins stable. This data can now drive the design process.”

    Their study was supported by the Howard Hughes Medical Institute and the Natural Sciences and Research Council of Canada. Rocklin is a Merck Fellow of the Life Sciences Research Foundation. Arrowsmith holds a Canadian Research Chair in Structural Genomics.

    This work was facilitated by the Hyak supercomputer at the University of Washington and by donations of computing time from Rosetta@home participants.

    Rosetta@home project, a project running on BOINC software from UC Berkeley

    Dr. David Baker, Baker Lab, U Washington

    4
    Hyak supercomputer at the University of Washington

    See the full article here .

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.
    So what defines us —the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 7:09 am on June 27, 2017 Permalink | Reply
    Tags: , , , , , , Data visualisation isn’t just for communication it’s also a research tool, Managing large data sets, , Minardo, Protein Studies, Sequencing, Visualising networks that change over time, VIZBI - an international visualisation community   

    From CSIRO: “Data visualisation isn’t just for communication, it’s also a research tool” 

    CSIRO bloc

    Commonwealth Scientific and Industrial Research Organisation

    27th June 2017
    Seán I. O’Donoghue
    James B. Procter

    1
    A collage of biological data visualisations. Image from C. Stolte, B.F. Baldi, S.I. O’Donoghue, C. Hammang, D.K.G. Ma, and G.T. Johnson, CC BY.

    At the heart of the scientific method lies the ability to make sense from data.

    However, this is a challenge in the fast-moving field of biotechnology, where new experimental methods are creating huge amounts of complex data. These data promise to revolutionise healthcare, food and agriculture, but it can be difficult to extract answers to specific research questions from these sets of numbers.

    Data visualisation can help. Our eyes deliver information very rapidly to our brains, and then sophisticated pattern recognition abilities take over. Well-designed visualisation tools can reveal discoveries that would otherwise remain buried.

    Below we highlight three data visualisation tools we have developed to help life scientists find relevant and useful information among the noise. The visualisation principles used in these tools are general and help in many complex data challenges.

    Managing large data sets

    Proteins and other molecules in our bodies exist as complex 3D structures that constantly change shape and interact with each other. Mapping out the many possible ways that proteins can be structured helps scientists understand how biological processes work, and may inform drug development and treating diseases such as cancer.

    Thanks to decades of research worldwide, we now have reliable, evidence-based 3D structures for tens of thousands of proteins, plus more than 100 million models of protein structures.

    These models are useful for learning about life’s molecular processes – such as how RNA and proteins are made – however, the large number of models can make it difficult for scientists to pin down which specific models can help answer a particular research question.

    To address this difficulty, one of us (Seán O’Donoghue) and colleagues developed Aquaria, a tool using the visualisation principle of “overview first, details on demand”. By using a technique called “clustering”, Aquaria creates a concise visual overview of all structural models available for any specific protein.

    2
    An overview of all 3D structural models available for p53, a protein that protects against cancer. Image created using Aquaria. S.I. O’Donoghue and C. Stolte, Author provided.

    The image above shows this overview for p53, a protein that protects against cancer. Each cluster of related 3D models can be interactively expanded and explored (bottom of the image), helping scientists find the most useful models suited to address a specific research question.

    Once a suitable model is found it is shown (top of the image), with dark colouring used to indicate regions where the structure of the model is less certain. In addition, yellow, blue and green are used to highlight different shapes within the structure, which helps scientists understand how the protein is arranged in three dimensions.

    Viewing connections between different datasets

    Sometimes, we need to look at data from multiple viewpoints. This is particularly true for a field of research known as sequencing. Sequencing involves determining the precise order of the chemical building blocks that make up DNA, RNA and protein. Knowing these sequences and comparing how they vary between individuals can tell us about mutations that cause disease and reveal how we evolved.

    One of the most widely used tools for visualising sequences is Jalview, co-developed by one of us (James Procter), which brings together the huge amounts of data that are created through sequencing.

    Jalview employs two principles – “linking and brushing” and “multiple coordinated views” – to bring together different types of information. Jalview also allows other tools to be connected, enabling scientists to navigate through complex, interrelated datasets.

    The example below shows a family of proteins known as Aquaporins, which are molecular channels important for water balance and nutrient transport in cells. Aligning these protein’s sequences (close up on right) allows them to be clustered into a tree (shown top-left, with birds-eye view of the protein alignment next door). DNA mutations are mapped onto the protein alignment (shown in red), and these colours also locate the mutations in protein structure (bottom left).

    3
    Linked brushing and multiple data visualisations allow potential disease mutations to be identified at the core of Aquaporin, a protein important for water balance and nutrient transport. Image created using Jalview linked with UCSF Chimera. J.B. Procter, Author provided.

    Visualising networks that change over time

    Scientists are aiming to unravel diseases – such as obesity – by studying small changes that take place within our cells.

    For example, food that we eat triggers the release of insulin into our blood stream, which then tells fat cells to store rather than release energy. This process ultimately influences our body weight.

    Cells are tiny, but they are hives of activity. Thanks to recent advances in techniques such as mass spectrometry, we can now map the tens of thousands of events that are happening within each of our cells in response to hormones such as insulin.

    The difficulty for scientists is to try to view this huge amount of information in an accurate and simple way, and one that reflects the chain of events in a cell that matter to our overall health.

    One of us (Seán O’Donoghue) and colleagues developed Minardo, an approach that creates a sort of timeline of events that happen inside a cell. Minardo uses the principle that position on a viewing screen is the most effective visualisation strategy. The resulting visualisation helps scientists identify exactly what is going on inside a healthy cell, and what might be different in a diseased cell.

    The image here shows (beginning top left, then clockwise) the sequence of events that take place after insulin (in pink) binds to the surface of a fat cell. The consequences of insulin binding include switching off the release of energy stores from the cell (around 1 minute after insulin binds), and switching on energy storage (around 5 minutes after insulin binds).

    5
    The sequence of key events within a human fat cell following insulin binding to its receptor (top left, pink). Image created using Minardo. D.K.G. Ma, C. Stolte, J.R. Krycer, D.E. James, and S.I. O’Donoghue, Author provided.

    VIZBI, an international visualisation community

    In building these tools, we aim to visualise data as clearly as possible, so the viewer can focus on the science.

    Aquaria, Jalview and Minardo are freely accessible and used by tens of thousands of scientists and students worldwide – an accomplishment that we are proud of.

    However, our tools address only three specific research questions – biology has thousands more. Tailored visualisations of this kind need an interdisciplinary team, take months to prototype and require years to develop into robust and usable tools.

    Realising this, in 2010, we created an international initiative called VIZBI to connect tool-builders and raise the standard of data visualisation in biology. In June 2017, VIZBI and associated events came to the Asia-Pacific region for the first time.

    The overwhelming complexity of biological data, substantial time and effort is required to create effective visualisation tools not just for communication but also for research itself.

    Seán I. O’Donoghue, Senior Faculty Member at the Garvan Institute, Conjoint Professor at UNSW, and Senior Principal Research Scientist, CSIRO and James B. Procter, Jalview Coordinator, Bioinformatician and Open Source Software Developer, University of Dundee

    See the full article here .

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    CSIRO campus

    CSIRO, the Commonwealth Scientific and Industrial Research Organisation, is Australia’s national science agency and one of the largest and most diverse research agencies in the world.

     
  • richardmitnick 6:20 pm on June 26, 2017 Permalink | Reply
    Tags: , , , CrY2H-seq, Interactome, New method to rapidly map the “social networks” of proteins, Protein Studies,   

    From Salk: “New method to rapidly map the ‘social networks’ of proteins” 

    Salk Institute bloc

    Salk Institute for Biological Studies

    June 26, 2017

    Salk scientists improved upon a classic approach to mapping the interactions between proteins.

    1
    A new mapping method let researchers discover new links (gray lines) between two groups of plant proteins (yellow and blue) that have a common structure (the BBX domain), suggesting many different combinations of interactions, rather than a few, are involved in coordinating cellular programs like flowering time and circadian rhythm. Credit: Salk Institute

    Salk scientists have developed a new high-throughput technique to determine which proteins in a cell interact with each other. Mapping this network of interactions, or “interactome,” has been slow going in the past because the number of interactions that could be tested at once was limited. The new approach, published June 26 in Nature Methods, lets researchers test millions of relationships between thousands of proteins in a single experiment.

    “The power of this new approach is in the ability we now have to scale it up,” says senior author Joseph Ecker, professor and director of Salk’s Genomic Analysis Laboratory and investigator of the Howard Hughes Medical Institute. “This assay has the potential to begin to address questions about fundamental biological interactions that we haven’t been able to address before.”

    The interactome of a cell, like a map of social networks, lets scientists see who’s working with who in the world of proteins. This helps them figure out the roles of different proteins and piece together the different players in molecular pathways and processes. If a newly discovered protein interacts with lots of other proteins involved in cellular metabolism, for instance, researchers can deduce that’s a likely role for the new protein and potentially target it for treatments related to metabolic dysfunction.

    Until now, researchers have typically relied on standard high-throughput yeast two-hybrid (Y2H) assays to determine the interactions between proteins. The system requires using a single known protein—known as the “bait”—to screen against a pool of “prey” proteins. But finding all the interactions between, for instance, 1,000 proteins, would require 1000 separate experiments to screen once for each bait’s interaction partners.

    “Current technologies essentially require that interactions detected in primary screening get retested individually,” says Shelly Trigg, an NSF Graduate Research Fellow at the University of California, San Diego, in the Ecker lab, and first author of the new paper. “That may no longer be necessary with the screening depth this approach achieves.”

    In their new method, Ecker, Trigg and their colleagues added a twist to the standard Y2H assay for a much more effective way of measuring the interactome. The genes for two proteins, each on their own circle of DNA, are added to the same cell. If the proteins of interest interact inside the cell, a gene called Cre is activated. When turned on, Cre physically splices the two individual circles of DNA together, thus pairing the genes of interacting proteins together so the team can easily find them through sequencing. The team can generate a massive library of yeast cells—each containing different pairs of proteins by introducing random combinations of genes on circular DNA called plasmids. When cells are positive for a protein interaction, the researchers can use genetic sequencing to figure out what the two proteins interacting are, using new high-throughput DNA sequencing technologies similar to those used for human genome sequencing. This way, they’re no longer limited to testing one “bait” protein at a time, but could test the interactions between all the proteins in a library at once.

    3
    Joseph Ecker (courtesy of Salk Institute) and Shelly Trigg (courtesy of Austin Trigg)

    Ecker’s group tested the new method, dubbed CrY2H-seq, on all the transcription factors—a large class of proteins—in the plant Arabidopsis.

    “When you take 1,800 proteins and test the interactions among them, that’s nearly 4 million combinations,” says Ecker. “We did that ten times in a matter of a month.”

    They revealed more than 8,000 interactions among those proteins tested, giving them new insight into which Arabidopsis transcription factors interact with each other. The data, they say, helps answer longstanding questions about whether certain groups of transcription factors have set functions. Some of the poorly understood transcription factors, they found, interact with more well-understood factors that regulate the plant’s response to auxin, a hormone involved in coordinating plant growth.

    In the future, the method could be scaled up to test larger sets of proteins—human cells, for instance, contain about 20,000 different proteins. This easier and faster method to determine the entire interactome of a cell also opens up the possibility of studying how the interactome changes under different conditions—an experiment that’s never been possible in the past.

    Other researchers on the study were Renee Garza, Andrew MacWilliams, Joseph Nery, Anna Bartlett, Rosa Castanon, Adeline Goubil, Joseph Feeney, Ronan O’Malley, Shao-shan Carol Huang, Zhuzhu Zhang, and Mary Galli of the Salk Institute.

    The work and the researchers involved were supported by grants from the U.S. Department of Energy, National Science Foundation Graduate Research Fellowship Program, Howard Hughes Medical Institute, and Mary K. Chapman Foundation.

    See the full article here .

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    Salk Institute Campus

    Every cure has a starting point. Like Dr. Jonas Salk when he conquered polio, Salk scientists are dedicated to innovative biological research. Exploring the molecular basis of diseases makes curing them more likely. In an outstanding and unique environment we gather the foremost scientific minds in the world and give them the freedom to work collaboratively and think creatively. For over 50 years this wide-ranging scientific inquiry has yielded life-changing discoveries impacting human health. We are home to Nobel Laureates and members of the National Academy of Sciences who train and mentor the next generation of international scientists. We lead biological research. We prize discovery. Salk is where cures begin.

     
  • richardmitnick 10:25 am on June 8, 2017 Permalink | Reply
    Tags: , Garry Buchko, , , , Protein Studies, Tackling infectious disease — one protein at a time   

    From PNNL: “Tackling infectious disease — one protein at a time” 

    PNNL BLOC
    PNNL Lab

    June 08, 2017
    Tom Rickey
    tom.rickey@pnnl.gov
    (509) 375-3732

    1
    The structure of a protein named thioredoxin. Garry Buchko and colleagues used NMR to solve the structure of the protein, which is found in an infection often conveyed by ticks. Credit: SSGCID

    2
    A protein in the pathogen that causes cryptosporidiosis. The microbe can cause mild to severe diarrhea in people who accidentally swallow a mouthful of contaminated water. Credit: SSGCID

    3
    Buchko and colleagues solved this structure of a protein found in the organism that causes malaria. Credit: SSGCID

    4
    A protein in the microbe that causes melioidosis, which occurs most often in people who live in tropical climates. Infection often starts in the lungs when contaminated dust or soil is inhaled. Credit: SSGCID

    5
    A protein in the micro-organism that causes giardiasis, which translates to nausea, abdominal pain, fatigue and other symptoms in hundreds of millions of people worldwide each year. Credit: SSGCID

    Garry Buchko and his colleagues are at the front line battling some of the most fearsome enemies that humanity has ever known: Tuberculosis. Pneumonia. Ebola. Plague. Botulism.

    But he is not in a hospital or field tent, taking vital signs or administering medications. Instead, Buchko the biochemist is in the laboratory, where the front line is the world of proteins — the molecular workhorses that keep all organisms functioning properly and make life possible. Using some of the highest-tech approaches available, he works with scientists in the Pacific Northwest to uncover crucial information needed to develop better treatments or vaccines against a host of nasty agents that can cause body aches, nausea, fatigue, food poisoning, diarrhea, ulcers, difficulty breathing, and death.

    Buchko does such work as part of the Seattle Structural Genomics Center for Infectious Disease, one of two centers funded by the National Institute of Allergy and Infectious Diseases tasked with solving the structure of proteins that enable pathogens to live, thrive, and infect people. Scientists from four institutions partner in the effort: The Center for Infectious Disease Research, Beryllium Discovery Corp., the University of Washington, and the Department of Energy’s Pacific Northwest National Laboratory, where Buchko does his research.

    This week the team reached a milestone, announcing that its scientists have solved the 3-D structure of the 1,000th protein from more than 70 organisms that cause infectious disease in people. The proteins the team has studied come from microbes that cause several serious diseases, including tuberculosis, Listeria, Giardia, Ebola, anthrax, Clostridium difficile (C. diff) infection, Legionella, Lyme, chlamydia and the flu.

    While the proteins isolated for study are not pathogenic, the structural information provides scientists the opportunity to design molecules that will knock out an essential process in such microbes.

    It is challenging work. Protein shapes are very complex — many look a lot like convoluted roller coasters with multiple twists, turns, and loops, all squeezed into a tiny space just one ten-thousandth the width of a human hair. The arrangement and lengths of these features give each protein its specific biochemical properties — what other molecules they will interact with and precisely what they will do in the body. Knowing the precise shape of proteins provides a blueprint for scientists searching for new ways to disable the pathogens and stop the diseases they can cause.

    Buchko’s expertise is with nuclear magnetic resonance or NMR, which is very similar to the magnetic resonance imaging technique widely used by physicians to diagnose all manner of medical conditions. Buchko scrutinizes proteins from pathogens drawing upon the NMR technology at EMSL, the Environmental Molecular Sciences Laboratory, a DOE Office of Science user facility at PNNL.

    While the end result is an atomic-level picture, it’s not as simple as snapping a photograph. Instead, Buchko places the protein inside an NMR spectrometer and records information about the orientation, energy and other properties of all the atomic nuclei in the molecule. Then he interprets the information and feeds the thousands of pieces of data into a computer program to calculate the position of every atom, resulting in a complete 3-D reconstruction of the protein. Data analysis is crucial to getting the structures correct.

    Buchko has been an author on more than 20 of the team’s studies in the last 10 years. Among his targets are pathogens that cause tuberculosis, malaria, cat scratch fever, and hemorrhagic fevers, as well as water-based parasites that cause severe diarrhea and abdominal pain.

    SSGCID scientists have published more than 100 manuscripts detailing their findings. In addition, all the structures are immediately shared with the scientific community through a public database called the Protein Data Bank. As a result, the structures have been used in nearly 600 scientific papers from other laboratories in academia, research institutes, and pharmaceutical companies around the world that are working on human pathogens. Sharing its findings so that scientists worldwide can make further discoveries is at the heart of SSGCID’s mission.

    The Seattle-based center is one of two centers funded by NIAID (contract # HHSN272201200025C). The other, based in Chicago, is the Center for Structural Genomics of Infectious Diseases and includes another DOE laboratory, Argonne National Laboratory, among its participants. The SSGCID is led by Peter Myler, professor and director of core services at the Center for Infectious Disease Research.

    “When the SSGCID solves protein structures, it lays the foundation for researchers at CID Research and around the world to find new drugs, therapies and vaccine candidates for diseases that kill thousands each year,” said Myler. “I’m very proud of the hard work carried out by our team and our dedicated partners.”

    EMSL, the Environmental Molecular Sciences Laboratory, is a DOE Office of Science User Facility. Located at Pacific Northwest National Laboratory in Richland, Wash., EMSL offers an open, collaborative environment for scientific discovery to researchers around the world. Its integrated computational and experimental resources enable researchers to realize important scientific insights and create new technologies. Follow EMSL on Facebook, LinkedIn and Twitter.

    Full information about the structures the team has solved is available on the SSGCID web site.

    See the full article here .

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    Pacific Northwest National Laboratory (PNNL) is one of the United States Department of Energy National Laboratories, managed by the Department of Energy’s Office of Science. The main campus of the laboratory is in Richland, Washington.

    PNNL scientists conduct basic and applied research and development to strengthen U.S. scientific foundations for fundamental research and innovation; prevent and counter acts of terrorism through applied research in information analysis, cyber security, and the nonproliferation of weapons of mass destruction; increase the U.S. energy capacity and reduce dependence on imported oil; and reduce the effects of human activity on the environment. PNNL has been operated by Battelle Memorial Institute since 1965.

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