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May 14th, 2011

Designer Proteins Target Influenza Virus

A research article in the May 13, 2011 issue of Science demonstrates the use of computational methods to design new antiviral proteins not found in nature, but capable of targeting specific surfaces of flu virus molecules. One goal of such protein design would be to block molecular mechanisms involved in cell invasion and virus reproduction. Computationally designed, surface targeting, antiviral proteins might also have diagnostic and therapeutic potential in identifying and fighting viral infections. The lead authors of the study are Drs. Sarel J. Fleishman and Timothy Whitehead of the University of Washington (UW) Department of Biochemistry, and Dr. Damian C. Ekiert from the Department of Molecular Biology and the Skaggs Institute for Chemical Biology at The Scripps Research Institute. The senior authors are Dr. Ian Wilson from Scripps and Dr. David Baker from the UW and the Howard Hughes Medical Institute. The researchers note that additional studies are required to see if such designed proteins can help in diagnosing, preventing, or treating viral illness. What the study does suggest is the feasibility of using computer design to create new proteins with antiviral properties. "Influenza presents a serious public health challenge," the researchers noted, "and new therapies are needed to combat viruses that are resistant to existing anti-viral medications or that escape the body's defense systems." The scientists focused their attention on the section of the flu virus known as the hemagglutinin stem region. They concentrated on trying to disable this part because of its function in invading the cells of the human respiratory tract.

May 14th

Giant Interneuron Enables Sparse Coding for Odors

The brain is a coding machine: it translates physical inputs from the world into visual, olfactory, auditory, tactile perceptions via the mysterious language of its nerve cells and the networks which they form. Neural codes could in principle take many forms, but in regions forming bottlenecks for information flow (e.g., the optic nerve) or in areas important for memory, sparse codes are highly desirable. Scientists at the Max Planck Institute for Brain Research in Frankfurt have now discovered a single neuron in the brain of locusts that enables the adaptive regulation of sparseness in olfactory codes. This single giant interneuron tracks in real time the activity of several tens of thousands of neurons in an olfactory center and feeds inhibition back onto all of them, so as to maintain their collective output within an appropriately sparse regimen. In this way, representation sparseness remains steady as input intensity or complexity varies. Signals from the world (electromagnetic waves, pressure, chemicals etc) are converted to electrical activity in sensory neurons and processed by neuronal networks in the brain. Insects sense smells via their antennae. Odors are detected by sensory neurons there, and olfactory data are then sent to and processed by the antennal lobes and a region of the brain known as the mushroom bodies. Neurons in the antennal lobes tend to be “promiscuous:” odors are thus represented by specific combinations of neuronal activity. Neurons in the mushroom bodies—they are called Kenyon cells—, however, respond with great specificity and thus extremely rarely. In addition, they generally respond with fewer than three electrical impulses when stimulated with the right odor.

May 12th

Gene Identified for Joubert Syndrome, a Type of Intellectual Disability

A new study involving Canada's Centre for Addiction and Mental Health (CAMH) has found a gene connected with a type of intellectual disability called Joubert syndrome. CAMH Senior Scientist Dr. John Vincent has identified this gene that, when defective, leads to Joubert syndrome. This research is published in the May 13, 2011 issue of Cell. This international study combined Dr. Vincent's gene mapping of a family with Joubert syndrome, with the use of a protein network map established by researchers at Genentech Inc., Stanford University, and the University of California at San Francisco (UCSF). Together, these approaches identified two genes associated with the group of disorders called ciliopathies. Joubert syndrome, which is a ciliopathy, affects brain functioning, resulting in intellectual deficits, movement and coordination problems, and other symptoms such as kidney and eye problems. This syndrome is reported to affect approximately 1 in 100,000 children, although this is likely to be a significant underestimate of the true prevalence. Ciliopathies are caused by genetic defects in a part of the cell called the cilium. The cilium is crucial as it is involved with cell signaling pathways during cell development in different parts of the body. The other ciliopathy gene identified in this study leads to a condition called nephronopthisis, which is also associated with kidney and eye problems. "A defect in any aspect of this molecular pathway may have very similar effects at the clinical level," says Dr. Vincent, who is also head of the Centre for Addiction and Mental Health's Molecular Neuropsychiatry and Development Laboratory. Dr. Vincent's team found defects in the TCTN2 gene occurring in a family in Pakistan, in which four siblings had Joubert syndrome.

May 11th

Personalized Medicine 4.0 Conference: Focus on Pharmacogenomics & Consumer Genetic Testing

This year’s Personalized Medicine Conference (4.0) will be held Thursday, May 26 from 8 am to 7 pm at the South San Francisco Conference Center on the campus of San Francisco State University. This fourth annual conference on personalized medicine focuses on two exciting areas – pharmacogenomics (the right drug, at the right dose, for the right patient, at the right time) and the controversial topic of direct-to-consumer genetic testing, examining the science, the business, and the social dimensions of each. Personalized Medicine 4.0 is a one-day conference and networking opportunity for health and industry professionals, educators, and scientists. Learn how the new genomic medicine will affect your work and your life. Seating is limited. Register now at http://personalizedmedicine.sfsu.edu. For additional information or to sponsor this event, please e-mail dnamed@sfsu.edu or call Arlene Essex at 415-405-4107. Advance registration is $495 through 5/16. Save $100 – Early registration is $395 ending soon! Contact us for academic rates.

Evolutionary Adaptations Can Be Reversed, But Rarely

Ever since Charles Darwin proposed his theory of evolution in 1859, scientists have wondered whether evolutionary adaptations can be reversed. Answering that question has proved difficult, partly due to conflicting evidence. In 2003, scientists showed that some species of insects have gained, lost, and regained wings over millions of years. But a few years later, a different team found that a protein that helps control cells’ stress responses could not evolve back to its original form. Dr. Jeff Gore, assistant professor of physics at MIT, says the critical question to ask is not whether evolution is reversible, but under what circumstances it could be. “It’s known that evolution can be irreversible. And we know that it’s possible to reverse evolution in some cases. So what you really want to know is: What fraction of the time is evolution reversible?” he says. By combining a computational model with experiments on the evolution of drug resistance in bacteria, Dr. Gore and his students have, for the first time, calculated the likelihood of a particular evolutionary adaptation reversing itself. They found that a very small percentage of evolutionary adaptations in a drug-resistance gene can be reversed, but only if the adaptations involve fewer than four discrete genetic mutations. The findings will appear in the May 13 issue of the journal Physical Review Letters. Lead authors of the paper are two MIT juniors, Longzhi Tan and Stephen Serene. Dr. Gore and his students used an experimental model system developed by researchers at Harvard University to study the evolution of a gene conferring resistance to the antibiotic cefotaxime in bacteria. The Harvard team identified five mutations that are crucial to gaining resistance to the drug.

Beneficial Bacteria Help Repair Intestinal Injury by Inducing Reactive Oxygen Species

The gut may need bacteria to provide a little bit of oxidative stress to stay healthy, new research suggests. Probiotic bacteria promote healing of the intestinal lining in mice by inducing the production of reactive oxygen species, researchers at Emory University School of Medicine have shown. The results, published online on May 9, 2011, in PNAS, demonstrate a mechanism by which bacterial cultures in foods such as yogurt and kimchi have beneficial effects on intestinal health. The insights gained could also guide doctors to improved treatments for intestinal diseases, such as necrotizing enterocolitis in premature babies or intestinal injury in critically ill adults. The laboratories of Dr. Andrew Neish and Dr. Asma Nusrat, both professors of pathology and laboratory medicine, teamed up for the study. The paper’s co-first authors are postdoctoral fellow Dr. Philip Swanson and associate research professor Dr. Amrita Kumar. “It’s been known for years that probiotic bacteria can have these kinds of helpful effects, but it wasn’t really clear how this worked,” Dr. Neish says. “We’ve identified one example, among many, of how certain kinds of bacteria have specific biochemical functions in the body.” Recent research has shown that the bacteria in our intestines influence our metabolism and immune systems. For example, an imbalance in the proportions of harmful and beneficial bacteria seems to over-activate immune cells in the intestines, driving inflammatory bowel disease. Intestinal epithelial cells, the cells that line the intestine, live in close contact with bacteria and normally form a barrier that keeps bacteria away from other organs. They can repair small gaps in the barrier, which breaks down in intestinal diseases, by migrating into the gaps.

May 9th

Salmonella enterica Regulates Virulence Based on Iron Levels

Salmonella enterica, one of the main causes of gastrointestinal infections, modulates its virulence gene expression, adapting it to each stage of the infection process, depending on the free iron concentration found in the intestinal epithelium of its host. Researchers at Universitat Autònoma de Barcelona (UAB) have demonstrated for the first time that the pathogen activates these genes through the Fur protein, which acts as a sensor of iron levels in its surroundings. The research, published online on May 6, 2011, in the journal PLoS ONE and entitled "Fur activates the expression of Salmonella enterica pathogenicity island 1 by directly interacting with the hilD operator in vivo and in vitro," was carried out by the Molecular Microbiology Group of the UAB Department of Genetics and Microbiology and coordinated by Dr. Jordi Barbé. Dr Juan Carlos Alonso from the National Biotechnology Centre also collaborated in the research group. Iron is an essential part of the development of almost all living organisms. This is why all organisms have developed an iron uptake system which guarantees that they can acquire it from their external environment. However, too much iron in the cell interior can have harmful effects and organisms have systems to control this as well. In vertebrates, this control produces a first defense barrier known as nutritional immunity which limits the amount of free iron found in biological fluids and prevents the development of pathogens. Only the upper intestinal track, given its anaerobic condition, presents appreciable levels of free iron.

May 9th

Nerve Cells’ Navigation System Revealed

Johns Hopkins scientists have discovered how two closely related proteins guide projections from nerve cells with exquisite accuracy, alternately attracting and repelling these axons as they navigate the most miniscule and frenetic niches of the nervous system to make remarkably precise connections. The discovery, reported April 28 in the journal Neuron and featured on the cover, reveals that proteins belonging to the "semaphorin" family of guidance cues are crucial for getting neuronal projections exactly where they need to be, not only across long distances, but also in the short-range wiring of tiny areas fraught with complex circuitry, such as the central nervous system of the fruit fly. Because signaling that affects the growth and steering of neuronal processes is critical for repairing and regenerating damaged or diseased nerve cells, this research suggests that a more refined understanding of how semaphorin proteins work could contribute to treatment strategies, according to Dr. Alex Kolodkin, a professor in the neuroscience department at Johns Hopkins and a Howard Hughes Medical Institute investigator. Using embryonic flies, some native (normal) and others genetically altered to lack a member of the semaphorin gene family or the receptor that binds to the semaphorin and signals within the responding neuron, the team labeled particular classes of neurons and then observed them at high resolution using various microscopy strategies to compare their axon projections. In the native developing flies, the team saw how certain related semaphorins, proteins that nerve cells secrete into the intracellular space, work through binding their plexin receptor. First, a semaphorin-plexin pair attracts a certain class of extending neurons in the embryonic fly central nervous system to assemble a specific set of target projections.

May 7th

Personalized Medicine 4.0 Conference: Focus on Pharmacogenomics & Consumer Genetic Testing

This year’s Personalized Medicine Conference (4.0) will be held Thursday, May 26 from 8 am to 7 pm at the South San Francisco Conference Center on the campus of San Francisco State University. This fourth annual conference on personalized medicine focuses on two exciting areas – pharmacogenomics (the right drug, at the right dose, for the right patient, at the right time) and the controversial topic of direct-to-consumer genetic testing, examining the science, the business, and the social dimensions of each. Personalized Medicine 4.0 is a one-day conference and networking opportunity for health and industry professionals, educators, and scientists. Learn how the new genomic medicine will affect your work and your life. Seating is limited. Register now at http://personalizedmedicine.sfsu.edu. For additional information or to sponsor this event, please e-mail dnamed@sfsu.edu or call Arlene Essex at 415-405-4107. Advance registration is $495 through 5/16. Save $100 – Early registration is $395 ending soon! Contact us for academic rates.

Temperature Shifts Prime Immune Response

Researchers at The Scripps Research Institute and the Novartis Research Foundation have found a temperature-sensing protein within immune cells that, when tripped, allows calcium to pour in and activate an immune response. This process can occur as temperature rises, such as during a fever, or when it falls—such as when immune cells are "called" from the body's warm interior to a site of injury on cooler skin. The study, published online on April 17, 2011 in Nature Chemical Biology, is the first to find such a sensor in immune cells—specifically, in the T lymphocytes that play a central role in activation of killer immune cells. The protein, STIM1, previously known as an endoplasmic reticulum (ER) calcium sensor, had been thought to be important in immune function, and now the scientists show it is also a temperature sensor. "Temperature has a profound effect on all biological processes including immune responses, but surprisingly little is known about molecules in immune cells that sense temperature shifts," said the study's principal investigator, Scripps Research Professor Ardem Patapoutian. "Here we show that STIM1 senses temperature and has a profound impact on immune cells." This is the second family of thermosensation molecules that the Patapoutian laboratory has uncovered. The team has isolated and characterized three of six members of the transient receptor potential (TRP) family of ion channels—the so-called thermoTRPs. "These proteins translate temperature, which is a physical stimulus, into a chemical signal—ions flowing into cells," said Dr. Patapoutian. "ThermoTRPs mainly function in specialized sensory neurons that relay environmental temperature information to the brain." In this study, the researchers turned to immune cells to look for temperature sensors.