SALK INSTITUTE FOR BIOLOGICAL STUDIES

Programs: Scientists help explain visual system's remarkable ability to recognize complex objects - in a complementary pair of studies published in neuron and the proceedings of the national academy of sciences, a team of salk neuroscientists has advanced the understanding of translation invariance-how the brain distinguishes different visual stimuli even as the stimuli move around in space. They discovered that in a part of the visual cortex called area v4, neurons have a large receptive field that can compute complex shapes such as contours. But they learned there is a trade-off between the complexity of the stimulus and the degree to which a neuron can recognize it as it moves from place to place. Understanding how the brain processes information to create a visual image might one day allow for direct stimulation of neurons in the cortex, allowing blind humans to regain sight. Such understanding also holds value for building computer systems that act more like humans. [7/1/13] unique epigenomic code identified during human brain development - in a study published in science, salk researchers showed that the landscape of dna methylation, a particular type of epigenomic modification, is highly dynamic in brain cells during the transition from birth to adulthood, helping to understand how information in the genomes of cells in the brain is controlled. They identified the exact sites of dna methylation and found that one form is present in neurons and glia from birth while a second form, almost exclusive to neurons, accumulates as the brain matures, becoming the dominant form of methylation in the genome of human neurons. This new information forms a critical foundation for exploring whether changes in methylation patterns may be linked to human diseases, including psychiatric disorders. [7/4/13] salk scientists add new bond to protein engineering toolbox - because proteins are the workhorses of cells, adopting conformations that allow them to set off chemical reactions, send signals and transport materials, scientists who are designing new drugs often engineer their own novel proteins. But linking two parts of a protein in a predictable and permanent way has been notoriously hard. As reported in nature methods, salk researchers have developed a new tool for protein engineering. They began by creating a new amino acid, different from the 20 that exist naturally, called p-2-fluoroacetyl-phenylalanine, or ffact. They then designed three proteins using ffact in their sequences. Tests of the proteins showed that they formed a covalent bond with ffact that was both irreversible and had just the right strength. The team plans to create additional amino acids that can form other kinds of bonds, adding more tools to the protein engineering kit that is so important to designing new drugs, imaging agents or molecules that aid basic research. [8/5/13] potent mechanism helps viruses shut down body's defense system against infection - a team of salk scientists has uncovered a previously unknown mechanism of enveloped viruses (common viruses with an outer wrapping of a lipid membrane) that inhibits the body's normal antiviral response and published their findings in cell host and microbe. The researchers learned that a substance called phosphatidylserine (ptdser), found on the surface of enveloped viruses, binds to extracellular proteins and activates tam receptors on immune cells. Tam receptor activation turns off a set of genes called interferons that play a key role in antiviral defense. Understanding this mechanism has allowed the team to begin testing small-molecule drugs that block the virus's ability to activate tam receptors, a novel approach that may prove effective against such viruses as west nile, dengue, influenza, ebola, marburg and hepatitis b. [8/14/13] drug blocks light sensors in eye that may trigger migraine attacks - a previous discovery at the salk institute showed that melanopsin, a receptor found in neurons connecting the eyes and brain, is responsible for sensing light independently of normal vision, and is also vital for maintaining sleep cycles, constricting the pupil in bright light and potentially exacerbating the light-sensitivity associated with migraine headaches. Building on that discovery, salk researchers have identified a group of chemicals dubbed opsinamides that selectively blocks melanopsin. Testing in mice proved that opsinamides stop melanopsin from signaling the brain when the eyes are exposed to bright light. The study, published in nature chemical biology, could help people with migraines or circadian rhythm imbalances maintain normal work schedules and productivity. [8/26/13] insulin plays a role in mediating worms' perceptions and behaviors - to better understand how information travels through the brain, scientists study neural connections. In an article published in nature neuroscience, salk scientists reported a striking discovery of flexibility in neural circuitry and detailed its influence on behaviors in the roundworm caenorhabditis elegans. By exposing the worm to salt within a certain concentration range, the team found that, as opposed to previous belief, more than one type of neuron is involved in processing sensory cues, and that the olfactory neuron was crucial for the worm's movement toward the salt. Additionally, they discovered that an insulin neuropeptide, subsequently identified as ins-6, was being released by the salt-sensing neuron to shape the animal's behavior. Similar neuropeptide communication may create flexible neural circuits that mediate the diverse behaviors that animals and people perform in their environments. This study adds important new data to our knowledge of how the human brain functions. [9/13/13] induced pluripotent stem cells reveal differences between humans and great apes - for the first time, chimpanzee and bonobo skin cells have been turned into induced pluripotent stem cells (ipscs) by a team at the salk. Scientists regularly use ipscs to model diseases and this new advancement will be used to explore some of the evolutionary differences between humans and non-human primates. The team has already found disparities in the regulation of jumping genes-dna elements that copy and paste themselves into spots throughout the genome-between humans and non-human primate cells. Jumping genes allow the rapid shuffling of dna and, according to the scientists, may be shaping the evolution of our genomes. As published in nature, the study reported that jumping genes appear to be more restricted in humans than in chimpanzees or bonobos. Further comparison and examination of the ispcs will provide clues to better understanding biological processes, such as infection, diseases, brain evolution, adaptation and genetic diversity. [10/23/13] generating "mini-kidney" structures from human stem cells may lead to much-needed therapies for kidney disease - in pioneering work that science magazine named runner-up for 2013 breakthrough of the year, a team of salk scientists became the first to coax human stem cells into forming three-dimensional cellular structures similar to those found in human kidneys. The findings were reported in nature cell biology. To test their protocol, the team collected induced pluripotent stem cells (ipscs) from a patient with a genetic disorder known as polycystic kidney disease (pkd), then produced kidney structures from the patient-derived ipscs. Because of the many clinical manifestations of pkd, neither gene- nor antibody-based therapies are realistic approaches for treatment. This unprecedented technique might provide a reliable platform for developing drug-based therapeutics for pkd and other kidney conditions. [11/17/13] connecting the dots between genes and human behavior - salk scientists partnering with an international team have advanced the understanding of how genes influence brain structure and cognitive abilities and how neural circuits produce language. They studied individuals with a rare disorder known as williams syndrome which imparts learning disabilities but also gifts a sociable nature and remarkable verbal and facial recognition abilities. Using sensors to measure brain activity, the researchers presented study participants with both visual and auditory stimuli and charted the small changes in voltage generated by different areas of the brain. They discovered that the ventral portion of the brain appeared to exhibit plasticity in analyzing information. They also found that williams is due not to a single gene but to distinct subsets of genes, hinting that the syndrome is more complex than originally thought. The results, published in developmental neuropsychology, may lead to new insight into such disorders as autism, down syndrome and schizophrenia. [11/27/13] missing molecule in chemical production line discovered - isoprenoids, a diverse class of molecules found in every living organism, are derived from a common building block molecule