SALK INSTITUTE FOR BIOLOGICAL STUDIES
10010 N TORREY PINES ROAD, LA JOLLA, CA 920371002 www.salk.edu

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Organizations Filed Purposes: INVOLVED IN RESEARCH ACTIVITIES, THE OBJECTIVES OF WHICH ARE THE ADVANCEMENT AND DISSEMINATION OF KNOWLEDGE RELEVANT TO THE HEALTH AND WELLBEING OF MAN. THE OBJECTIVES ARE MET PRIMARILY THROUGH RESEARCH AND ADVANCED INSTRUCTION IN (A) BIOLOGY, (B) THE CAUSE, PREVENTION AND CURE OF DISEASES, AND (C) THE FACTORS AND CIRCUMSTANCES CONDUCIVE TO THE FULFILLMENT OF MAN'S BIOLOGICAL POTENTIAL.

BASIC RESEARCH IN THE FOLLOWING: MOLECULAR BIOLOGY & GENETICS, NEUROSCIENCE, AND PLANT BIOLOGY.

New computational tool lets researchers identify cells based on their chromosome shape - In the nucleus of every living cell, long strands of DNA are tightly folded into compact chromosomes. Now, thanks to a new computational approach developed by Professor Joseph Ecker, researchers can use the architecture of these chromosome folds to differentiate between types of cells. The development, published in the Proceedings of the National Academy of Sciences on July 8, will give scientists a better understanding of how interactions between different regions of DNA play a role in health and disease. [7/8/2019] Gene identified that will help develop plants to fight climate change - Hidden underground networks of plant roots snake through the earth foraging for nutrients and water, similar to a worm searching for food. Yet, the genetic and molecular mechanisms that govern which parts of the soil roots explore remain largely unknown. Now, Associate Professor Wolfgang Busch and his lab have discovered a gene that determines whether roots grow deep or shallow in the soil. The findings, published in Cell on July 11, will allow Salk researchers to develop plants that can help combat climate change as part of Salk's Harnessing Plants Initiative. [7/11/2019] Scratching the surface of how your brain senses an itch - Professor Martyn Goulding's lab has discovered how neurons in the spinal cord help transmit itch signals to the brain. Published in the journal Cell Reports on July 16, the team's findings help contribute to a better understanding of itch and could lead to new drugs to treat chronic itch, which occurs in such conditions as eczema, diabetes and even some cancers. [8/1/2019] How mammals' brains evolved to distinguish odors is nothing to sniff at - The world is filled with millions upon millions of distinct smells, but how mammals' brains evolved to tell them apart is something of a mystery. Now, Charles Stevens, Salk distinguished professor emeritus, in collaboration with UC San Diego, has discovered that at least six types of mammals-from mice to cats-distinguish odors in roughly the same way, using circuitry in the brain that's evolutionarily preserved across species. The work is published in Current Biology on July 18. [7/18/2019] Unlocking therapies for hard-to-treat lung cancers - A Salk study found that diabetes drug candidates may work against types of non-small-cell lung cancers. The discovery shows that researchers could target these hard-to-treat cancers by pursuing drugs that keep a cellular "switch," called CREB, from triggering tumor growth. The work, published in the journal Science Advances on July 24, was led by Salk Professor Marc Montminy, in close collaboration with Professor Reuben Shaw, and colleagues. [7/24/2019] Labs identify novel targets for deadly lung cancer - The lab of Professor Reuben Shaw discovered why a mutated gene called LKB1 results in non-small-cell lung cancer. The surprising results, published in Cancer Discovery on July 26, highlight how a non-mutated LBK1 communicates with two enzymes to block tumor growth. In the second study, published in the journal Science Advances on July 24 and led by Professor Marc Montminy in close collaboration with Shaw, the researchers targeted these hard-to-treat cancers by keeping a cellular "switch," called CREB, from triggering tumor growth. Together, the findings could lead to new therapies for lung cancer. [7/26/2019] Brain's astrocytes play starring role in long-term memory - Professor Terrence Sejnowski discovered that star-shaped cells called astrocytes, long considered to be merely supportive cells, help the brain establish long-lasting memories. The study, published in the journal GLIA on July 26, could inform therapies for disorders in which long-term memory is impaired, such as traumatic brain injury or dementia. [8/22/2019] Finding a cause of neurodevelopmental disorders - Neurodevelopmental disorders arising from rare genetic mutations can cause atypical cognitive function, intellectual disability and developmental delays, yet it is unclear why and how this happens. Now, Assistant Professor Diana Hargreaves has identified the molecular mechanism linking a mutation in a complex of proteins with abnormal nervous system development. The team's findings, published in Molecular Cell on July 30, bring researchers one step closer to understanding neurodevelopmental disorders. [7/30/2019] Salk scientists develop a new genome-editing tool that could help treat many disorders caused by gene mutations - The lab of Professor Juan Carlos Izpisua Belmonte developed a new tool-dubbed SATI-to edit the mouse genome, enabling the team to target a broad range of mutations and cell types. The new genome-editing technology, described in Cell Research on August 23, could be expanded for use in a broad range of gene mutation conditions such as Huntington's disease and the rare premature aging syndrome, progeria. [8/23/2019] New target for autoimmune disease could enable therapies with fewer side effects - Salk scientists led by Professor Ronald Evans and Associate Professor Ye Zheng have discovered a way to stop certain immune system cells from mistakenly attacking the body. Their findings, published in Proceedings of the National Academy of Sciences on August 26, suggest a new method to target a type of helper T cell that produces interleukin 17, a molecule known to be at the root of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and psoriasis. [8/27/2019] Getting to the root of how plants tolerate too much iron - Despite dozens of attempts in the last two decades to uncover the genes responsible for the iron tolerance of plants, these remained elusive. But recently, Associate Professor Wolfgang Busch and colleagues uncovered a gene credited with helping plants thrive in stressful environments. The team believes their finding, published in Nature Communications on August 29, could help plants, such as rice, become more resistant to iron in regions with toxic iron levels. [8/29/2019] Key enzyme found in plants could guide development of medicines and other products - Professor Joseph Noel 's lab discovered how an enzyme called chalcone isomerase evolved to enable plants to make products vital to their own survival. The study appeared in the journal version of ACS Catalysis on September 6. Researchers hope this knowledge will inform the manufacture of products that are beneficial to humans, including medications and improved crops. [9/6/2019] New technique reveals epigenetic features of cells in the brain - Understanding the large diversity of cells of the prefrontal cortex has long been challenging for researchers. Now, a team of scientists from the labs of Salk Professor Joseph Ecker and Salk Fellow Jesse Dixon has developed a method to simultaneously analyze how chromosomes, along with their epigenetic features, are compacted inside of single human brain cells. The work, published in Nature Methods on September 9, paves the way toward a new understanding of how some cells become dysregulated to cause disease. [9/9/2019] How emotion affects action - Salk Associate Professor Xin Jin and colleagues have discovered a direct link from the brain's emotion circuit to the movement circuit, which may explain such phenomena as athletes experiencing a rapid decline in performance under pressure, known as "choking." Now, the team has uncovered what might be behind it: one-way signals from the brain's emotion circuit to the movement circuit. The study, published in eLife on September 6, could lead to new strategies for treating disorders with disrupted movement, such as obsessive-compulsive disorder, anxiety and depression. [9/10/2019] Salk scientists find way to quantify how well cutting-edge microscopy technique works - In 2017, the lab of Assistant Professor Dmitry Lyumkis reported that tilting a frozen protein sample as it sat under an electron microscope was an effective approach to acquiring better information about its structure and helping researchers understand a host of diseases ranging from HIV to cancer. Now, they have developed a mathematical framework that underlies some of those initial observations. Their new study, published in Progress in Biophysics and Molecular Biology on September 13, provides a foundation for determining how differences in viewing angles affect the resulting 3D structures of proteins, and could help other researchers determine the best setup for experiments to improve the imaging technique called cryo-EM. [10/3/2019] Study yields insights that may improve immunotherapy for melanoma - Although immunotherapy is revolutionizing cancer treatment, many patients do not respond. Now, Salk Professors Susan Kaech and Gerald Shadel, along with colleagues in Israel and the U.S., have revealed a unique connection between fat metabolism by melanoma tumor cells and patient response to immunotherapy. More specifically, they found that the f

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