The Salk Institute for Biological Studies

THE SALK INSTITUTE FOR BIOLOGICAL STUDIES IS A WORLD-RENOWED, INDEPENDENT RESEARCH INSTITUTE DEDICATED TO ADVANCING OUR UNDERSTANDING OF LIFE SCIENCES AND IMPROVING HUMAN HEALTH. ITS PROGRAMS BRING TOGETHER LEADING SCIENTISTS ACROSS DISCIPLINES TO EXPLORE FUNDAMENTAL QUESTIONS IN BIOLOGY, FROM THE MOLECULAR MECHANISMS OF DISEASE TO THE COMPLEXITIES OF THE BRAIN AND THE IMPACT OF CLIMATE CHANGE ON LIVING SYSTEMS. THROUGH COLLABORATIVE, CURIOSITY-DRIVEN RESEARCH AND INNOVATIVE TECHNOLOGY, SALK'S PROGRAMS AIM TO TRANSLATE SCIENTIFIC DISCOVERIES INTO REAL-WORLD SOLUTIONS THAT BENEFIT SOCIETY. BELOW ARE HIGHLIGHTED SCIENTIFIC ACHIEVEMENTS DURING JULY 2024 THROUGH JUNE 2025. STUDY REVEALS KEY GENE PROTECTING PLANTS FROM HARMFUL METALS IN SOIL - THE EXCESSIVE USE OF MANURE AND SEWAGE SLUDGE CAN INCREASE HEAVY METAL CONCENTRATIONS IN AGRICULTURAL LAND WHERE VITAL CROPS ARE GROWN. ONE OF THESE HEAVY METALS IS ZINC, A MICRONUTRIENT NECESSARY FOR PLANT AND ANIMAL HEALTH. IN EXCESS, HOWEVER, ZINC CAN BE EXTREMELY DAMAGING TO SENSITIVE PLANT SPECIES. SALK RESEARCHERS IDENTIFIED A GENE, CALLED TRICHOME BIREFRINGENCE OR TBR, THAT HELPS PLANTS MANAGE EXCESS ZINC BY TRAPPING IT IN THEIR ROOT CELL WALLS. SCIENTISTS AND FARMERS CAN NOW USE THIS INFORMATION TO DEVELOP AND GROW CROPS THAT ARE MORE RESILIENT TO SOIL CONTAMINATION. ENHANCING PLANT RESILIENCE IN THIS WAY IS A MAJOR GOAL OF SALK'S HARNESSING PLANTS INITIATIVE. THE STUDY WAS LED BY WOLFGANG BUSCH, PHD, AND PUBLISHED IN NATURE COMMUNICATIONS ON JULY 11, 2024. NEW TOOLS REVEAL NEUROPEPTIDES, NOT FAST NEUROTRANSMITTERS, ENCODE DANGER IN THE BRAIN - IN THE SPLIT SECOND THAT YOU ACCIDENTALLY TOUCH THE HOT HANDLE OF A CAST IRON SKILLET, PAIN AND A SENSE OF DANGER RUSH IN. RESEARCHERS ASSUMED THIS PROCESS MUST BE MEDIATED BY FAST-ACTING NEUROTRANSMITTERS, BUT SALK RESEARCHERS CREATED TWO NEW TOOLS TO STUDY THE EMOTIONAL FEAR RESPONSE CIRCUIT IN LIVE MICE FOR THE FIRST TIME. THEY FOUND THAT LARGER, SLOWER MOLECULES CALLED NEUROPEPTIDES ARE THE MAIN MESSENGERS IN THIS CIRCUIT-AND MORE THAN ONE NEUROPEPTIDE IS INVOLVED. THEIR FINDINGS MAY EXPLAIN WHY EXISTING MEDICATIONS THAT TARGET ONLY ONE NEUROPEPTIDE ARE OFTEN INEFFECTIVE AND COULD INSPIRE THE DEVELOPMENT OF NEW TREATMENTS FOR FEAR-RELATED CONDITIONS LIKE ANXIETY AND PTSD. THE STUDY WAS LED BY SUNG HAN, PHD, AND PUBLISHED IN CELL ON JULY 22, 2024. FUEL LEVEL LOW! ENERGY DEFICITS HARM ATHLETES' HEALTH, NEW RESEARCH TOOL REVEALS HOW - RELATIVE ENERGY DEFICIENCY IN SPORT, OR REDS, IS ESTIMATED TO AFFECT MORE THAN 40% OF PROFESSIONAL ATHLETES-AND THE RATE COULD BE EVEN HIGHER IN RECREATIONAL ATHLETES AND EXERCISERS. ATHLETES DEVELOP REDS BY CONSISTENTLY EXPENDING MORE ENERGY THAN THEY TAKE IN. OVER TIME, THIS ENERGY DEFICIT CAN LEAD TO HORMONAL AND REPRODUCTIVE ISSUES, INSOMNIA AND FATIGUE, BONE WEAKNESS AND INJURY, AND A HIGHER RISK OF ANXIETY AND DEPRESSION. SALK SCIENTISTS CREATED A LANDMARK MOUSE MODEL OF REDS, WITH WHICH THEY FOUND THAT REDS AFFECTS ORGAN SIZE AND GENE EXPRESSION PATTERNS ACROSS THE ENTIRE BODY. WHAT'S MORE, THE SYNDROME APPEARS TO IMPACT MALE AND FEMALE MICE DIFFERENTLY, IMPACTING KIDNEY HEALTH THE MOST IN MALES AND REPRODUCTIVE HEALTH AND MUSCLE MASS IN FEMALES. THIS WORK COULD IMPROVE REDS DIAGNOSIS AND REVEAL MOLECULAR TARGETS FOR FUTURE THERAPEUTICS TO HALT, REVERSE, OR PREVENT THE SYNDROME. THE STUDY WAS LED BY SATCHIDANANDA PANDA, PHD, AND PUBLISHED IN CELL METABOLISM ON SEPTEMBER 3, 2024. ONE IN THREE AMERICANS HAS A DYSFUNCTIONAL METABOLISM, BUT INTERMITTENT FASTING COULD HELP - MORE THAN ONE-THIRD OF ADULTS IN THE UNITED STATES HAVE METABOLIC SYNDROME, A CLUSTER OF CONDITIONS THAT SIGNIFICANTLY RAISE A PERSON'S RISK OF HEART DISEASE, STROKE, AND TYPE 2 DIABETES. THESE CONDITIONS INCLUDE HIGH BLOOD PRESSURE, ELEVATED BLOOD SUGAR, EXCESS ABDOMINAL FAT, AND ABNORMAL CHOLESTEROL LEVELS. IN A NEW CLINICAL TRIAL, RESEARCHERS AT SALK AND UC SAN DIEGO FOUND THAT TIME-RESTRICTED EATING-ALSO KNOWN AS INTERMITTENT FASTING-COULD OFFER SIGNIFICANT HEALTH BENEFITS TO ADULTS WITH METABOLIC SYNDROME. COMPARED TO OTHER PRESCRIBED LIFESTYLE CHANGES, TIME-RESTRICTED EATING COULD OFFER A MORE PRACTICAL INTERVENTION ACCESSIBLE TO A WIDER RANGE OF PATIENTS. THE STUDY WAS LED BY SATCHIDANANDA PANDA, PHD, AND PUBLISHED IN ANNALS OF INTERNAL MEDICINE ON OCTOBER 1, 2024. NEW BRAIN-MAPPING TOOL MAY BE THE "START" OF NEXT-GENERATION THERAPEUTICS - WHEN REPAIRING A CAR, IT'S IMPORTANT TO UNDERSTAND ITS BASIC BLUEPRINT AND HOW ALL THE PARTS CONNECT. TREATING BRAIN DISORDERS IS NO DIFFERENT, EXCEPT THAT SCIENTISTS ARE STILL MISSING KEY DETAILS OF THE BRAIN'S WIRING DIAGRAM. TO ADDRESS THIS, SALK RESEARCHERS DEVELOPED A NEW BRAIN-MAPPING TECHNOLOGY CALLED START. THE CUTTING-EDGE TOOL ALLOWS NEUROSCIENTISTS TO TRACE THE CONNECTIVITY BETWEEN DIFFERENT TYPES OF BRAIN CELLS WITH UNPRECEDENTED RESOLUTION. USING THIS TECHNIQUE, THE RESEARCHERS BECAME THE FIRST TO RESOLVE CORTICAL CONNECTIVITY AT THE RESOLUTION OF TRANSCRIPTOMIC CELL TYPES. THE DISCOVERIES MADE WITH START WILL HELP RESEARCHERS DESIGN NEW THERAPEUTICS THAT CAN TARGET CERTAIN NEURONS AND BRAIN CIRCUITS WITH GREATER SPECIFICITY AND EFFICACY, AND WITH FEWER SIDE EFFECTS THAN CURRENT PHARMACOLOGICAL APPROACHES. THE STUDY WAS LED BY EDWARD CALLAWAY, PHD, AND PUBLISHED IN IN NEURON ON SEPTEMBER 30, 2024. SCIENTISTS CREATE FIRST MAP OF DNA MODIFICATION IN THE DEVELOPING HUMAN BRAIN - A SALK, UC LOS ANGELES, UC SAN FRANCISCO, UC SAN DIEGO, AND SEOUL NATIONAL UNIVERSITY TEAM CREATED THE FIRST MAP OF DNA MODIFICATION IN THE HIPPOCAMPUS AND PREFRONTAL CORTEX-TWO REGIONS OF THE BRAIN CRITICAL TO LEARNING, MEMORY, AND EMOTIONAL REGULATION, AND ALSO FREQUENTLY INVOLVED IN DISORDERS LIKE AUTISM SPECTRUM AND SCHIZOPHRENIA. THE STUDY PROVIDES AN UNPRECEDENTED LOOK AT HOW GENE REGULATION EVOLVES DURING HUMAN BRAIN DEVELOPMENT, SHOWING HOW THE 3D STRUCTURE OF CHROMATIN (DNA AND PROTEINS) PLAYS A CRITICAL ROLE. THE PUBLICLY AVAILABLE ONLINE RESOURCE WILL BE A VALUABLE TOOL SCIENTISTS CAN USE TO CONNECT GENETIC VARIANTS ASSOCIATED WITH THESE CONDITIONS TO THE GENES, CELLS, AND DEVELOPMENTAL PERIODS THAT ARE MOST SENSITIVE TO THEIR EFFECTS. THE STUDY WAS LED BY JOSEPH ECKER, PHD, AND PUBLISHED IN NATURE ON OCTOBER 9, 2024. THROUGH THE LOOKING GLASS: A CROSS-CHIRAL REACTION CHALLENGES OUR DEFINITION OF LIFE - JUST AS YOUR LEFT AND RIGHT HANDS EXIST AS MIRROR IMAGES OF EACH OTHER, MANY BIOLOGICAL MOLECULES HAVE THEIR OWN FORM OF LEFT- AND RIGHT-HANDEDNESS, CALLED CHIRALITY. ON EARTH, ALL RNA EXISTS IN A RIGHT-HANDED CHIRAL FORM. EVEN WHEN SCIENTISTS MAKE SYNTHETIC LEFT-HANDED VERSIONS, THE TWO GROUPS BEHAVE AS IF ON OPPOSITE SIDES OF A MIRROR, UNABLE TO INTERACT WITH EACH OTHER. BUT WHAT IF THEY COULD? USING SOPHISTICATED BIOENGINEERING TECHNIQUES, SALK SCIENTISTS ENGINEERED A CHEMICAL SYSTEM IN WHICH LEFT- AND RIGHT-HANDED VERSIONS OF AN RNA ENZYME COULD EFFECTIVELY "REACH THROUGH THE MIRROR REPLICATE EACH OTHER EXPONENTIALLY AND INDEFINITELY. THIS IS THE FIRST EVIDENCE OF A LIFELIKE CHEMICAL SYSTEM THAT OPERATES ON BOTH SIDES OF THE MIRROR OF CHIRALITY, CREATING THE OPPORTUNITY TO STUDY AN ENTIRELY NEW FORM OF BIOCHEMICAL EVOLUTION. THE ACHIEVEMENT COULD ALSO ADVANCE THE DEVELOPMENT OF CROSS-CHIRAL THERAPEUTICS, DIAGNOSTICS, AND OTHER BIOTECHNOLOGIES. THE STUDY WAS LED BY GERALD JOYCE, MD, PHD, AND PUBLISHED IN PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES ON OCTOBER 22, 2024. CHOLESTEROL IS NOT THE ONLY LIPID INVOLVED IN TRANS FAT-DRIVEN CARDIOVASCULAR DISEASE - HIGH CHOLESTEROL HAS LONG BEEN THE FOCUS OF MANY HEART HEALTH CAMPAIGNS DUE TO ITS ROLE IN FORMING ARTERY-CLOGGING PLAQUES THAT CAN LEAD TO STROKE, HEART ATTACK, OR ARTERIAL DISEASE. BUT NEW SALK RESEARCH REVEALED THAT ANOTHER CLASS OF LIPIDS, CALLED SPHINGOLIPIDS, CAN ALSO CONTRIBUTE TO ARTERIAL PLAQUES AND HEART DISEASE. WHEN THE TEAM TRACKED THE FLOW OF DIETARY FATS THROUGHOUT THE BODY, THEY FOUND THAT TRANS FATS WERE BEING METABOLIZED INTO SPHINGOLIPIDS, AND THIS DROVE THE LIVER TO SECRETE ARTERY-CLOGGING MOLECULES INTO THE BLOODSTREAM. THE DISCOVERY THAT SPHINGOLIPIDS-NOT JUST CHOLESTEROL-CAN DIRECTLY CONTRIBUTE TO ATHEROSCLEROTIC HEART DISEASE OPENS A WHOLE NEW SET OF MOLECULES AND PATHWAYS THAT COULD BE TARGETED WITH NEW DRUGS TO WARD OFF CARDIOVASCULAR DISEASE, HEART ATTACK, AND STROKE. THE STUDY WAS LED BY CHRISTIAN METALLO, PHD, AND PUBLISHED IN CELL METABOLISM ON NOVEMBER 14, 2024.