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Salk Institute For Biological Studies, San Diego, California, The

Compare ↔
$30,893,832
Total funding
35
Grants

Funding over time

peak $5M · FY200825
$5M$3.8M$2.5M$1.3M$0
'08
'09
'10
'11
'12
'13
'14
'15
'16
'17
'18
'19
'20
'21
'22
'23
'24
'25

Funding mix

By agency

DOD$20,324,279 · 25
DOE$7,848,572 · 6
NASA$1,924,409 · 2
USDA$796,572 · 2

By mechanism

$30,893,832 · 35

Investigators at Salk Institute For Biological Studies, San Diego, California, The

InvestigatorsiAttributed = a PI's even-split share of each grant — a $1M grant with 2 PIs counts $500K each.
Exposure= the full size of every grant they're on ($1M each).

Rising Stars

First grant in the last 5 yrs

Not enough data

Emerging Leaders

6–10 yrs in

Not enough data

All-Time

Most funded here, all years

Not enough data

Largest grants

SINGLE CELL ANALYSIS FOR FORENSIC EPIGENETICS (SAFE)$4,778,942
· FY2019 · Department of the Army
PREVENTING THE TRANSMISSION OF MITOCHONDRIAL DISEASES THROUGH HETEROPLASMIC SHIFT$3,404,936
· FY2017 · Department of the Army
TAS::89 0222::TAS NEW; TITLE: NEXT GENERATION INTERACTOMES FOR PLANT SYSTEMS BIOLOGY AND BIOMASS FEEDSTOCKS RESEARCH; PI: JOSEPH ECKER$2,993,430
· FY2011 · Department of Energy
TISSUE-SPECIFIC AND DIURNAL PATTERN OF GENE EXPRESSION IN A NONHUMAN PRIMATE$1,477,826
· FY2018 · Department of the Army
MOLECULAR AND GENETIC ANALYSIS OF HORMONE REGULATED DIFFERENTIAL CELL ELONGATION IN ARABIDOPSIS$1,330,000
· FY2008 · Department of Energy
SIGNAL TRANSDUCTION PATHWAYS THAT REGULATE CAB GENE EXPRESSION$1,273,000
· FY2008 · Department of Energy
SIGNAL TRANSDUCTION PATHWAYS THAT REGULATE CAB GENE EXPRESSION$1,200,000
· FY2009 · Department of Energy
IMMUNOMODULATORS AS ADJUVANT ADDITIONS TO ENHANCE VACCINE RESPONSE$1,024,702
· FY2008 · Defense Threat Reduction Agency
EVOLUTION OF CATALYTIC RNA AND THE ORIGINS OF LIFE$1,000,379
· FY2022 · National Aeronautics and Space Administration
MICRORNA REPLACEMENT THERAPY FOR ALS TREATMENT$954,249
· FY2018 · Department of the Army
ANALYSIS OF ETHYLENE-REGULATED GROWTH NETWORKS IN ARABIDOPSIS$935,000
· FY2010 · Department of Energy
THE PROPOSED RESEARCH IS PART OF A NASA-SPONSORED EFFORT TO UNDERSTAND THE ORIGIN OF LIFE ON EARTH WHICH WILL GUIDE THE SEARCH FOR LIFE ELSEWHERE IN THE UNIVERSE. THE RESEARCH PERTAINS TO A FORM OF RNA-BASED LIFE THAT LIKELY EXISTED DURING EARTH S EARLY HISTORY AS A PREDECESSOR TO CURRENT DNA-RNA-PROTEIN-BASED LIFE. BUILDING ON PROGRESS MADE OVER THE PRIOR GRANT PERIOD THE CENTRAL AIM OF THE PROPOSED RESEARCH IS TO CONSTRUCT RNA-BASED LIFE IN THE LABORATORY AS REPRESENTED BY POPULATIONS OF RNA ENZYMES THAT CATALYZE THEIR OWN REPLICATION AND UNDERGO DARWINIAN EVOLUTION IN A SELF-SUSTAINED AND OPEN-ENDED MANNER. MOST OF THESE EFFORTS WILL FOCUS ON AN RNA POLYMERASE RIBOZYME THAT IS NOW ABLE TO SYNTHESIZE FUNCTIONAL RNAS AND TO CATALYZE THE EXPONENTIAL AMPLIFICATION OF SHORT RNAS. THE ENZYME IS NOT YET ABLE TO SYNTHESIZE ITSELF BUT THAT GOAL IS LIKELY TO BE ACHIEVABLE WITH ADDITIONAL OPTIMIZATION PRIMARILY BY EMPLOYING IN VITRO EVOLUTION METHODS TO ENHANCE THE RATE FIDELITY AND SEQUENCE GENERALITY OF THE POLYMERASE. ALTHOUGH THE AIM IS TO SYNTHESIZE THE POLYMERASE IN ITS ENTIRETY A DIVIDE-AND-CONQUER APPROACH ALSO WILL BE PURSUED WHEREBY THE ENZYME WILL BE DIVIDED INTO FRAGMENTS THAT CAN ASSEMBLE NON-COVALENTLY TO FORM A CATALYTIC COMPLEX WITH EACH OF THE FRAGMENTS (AND THEIR COMPLEMENTS) SYNTHESIZED BY THE ASSEMBLED COMPLEX. THIS APPROACH MAY REFLECT WHAT TRANSPIRED ON THE PRIMITIVE EARTH BUT ALSO EXPLORES A GENERAL PRINCIPLE FOR HOW DARWINIAN SYSTEMS MIGHT ARISE. THE DIVIDE-AND-CONQUER APPROACH HAS ALREADY BEEN USED FOR THE POLYMERASE RIBOZYME TO SYNTHESIZE ITS EVOLUTIONARY ANCESTOR AN RNA LIGASE RIBOZYME WHICH CAN BE DIVIDED INTO FRAGMENTS THAT ARE SYNTHESIZED SEPARATELY AND CAN ASSEMBLE NON-COVALENTLY TO FORM A FUNCTIONAL CATALYST. THIS APPROACH WILL BE EXTENDED TO THE SYNTHESIS OF LARGER AND MORE COMPLEX RNA ENZYMES INCLUDING THE POLYMERASE ITSELF. A SURPRISING DISCOVERY DURING THE PRIOR GRANT PERIOD WAS THAT HIGHLY OPTIMIZED FORMS OF THE RNA POLYMERASE RIBOZYME ALSO CAN FUNCTION AS A REVERSE TRANSCRIPTASE COPYING RNA TEMPLATES TO COMPLEMENTARY DNA PRODUCTS. THIS ACTIVITY WOULD HAVE BEEN CRUCIAL FOR THE TRANSITION FROM RNA TO DNA GENOMES DURING THE EARLY HISTORY OF LIFE. MORE RECENTLY IT WAS SHOWN THAT THE POLYMERASE CAN COPY DNA TEMPLATES TO RNA PRODUCTS AND AT LOWER EFFICIENCY COPY DNA TEMPLATES TO DNA PRODUCTS. FURTHERMORE RNA TEMPLATES CAN BE COPIED TO YIELD VARIOUS POLYNUCLEOTIDE ANALOGS MOST NOTABLY THREOSE NUCLEIC ACID (TNA) WHICH HAS BEEN SUGGESTED AS A POSSIBLE PREDECESSOR TO RNA. THESE ACTIVITIES WILL BE OPTIMIZED USING IN VITRO EVOLUTION TO GENERATE A FAMILY OF POLYMERASE RIBOZYMES THAT CAN BOTH AMPLIFY AND TRANSCRIBE MACROMOLECULAR INFORMATION IN VARIOUS FORMS. ALTHOUGH LIFE ON EARTH CAME TO ADOPT RNA AND ULTIMATELY DNA AS THE GENETIC MATERIAL A BROADER VIEW IS REQUIRED WHEN CONSIDERING THE POSSIBILITY OF LIFE ELSEWHERE. ONCE A SYSTEM IS IN HAND FOR THE SELF-SUSTAINED EVOLUTION OF RNA IT WILL BE POSSIBLE TO CONDUCT OPEN-ENDED RNA EVOLUTION EXPERIMENTS BOTH AS A WORKING MODEL OF RNA-BASED LIFE AND AS A MEANS TO EXPLORE THE DIVERSIFICATION OF RNA FUNCTION. THE PROMISE OF SUCH EXPERIMENTS WAS EXAMINED PREVIOUSLY USING A SELF-REPLICATING LIGASE RIBOZYME WHICH COULD BE MADE TO ADAPT TO DIFFERENT SELECTION CONSTRAINTS. HOWEVER THAT SYSTEM HAS A VERY LIMITED CAPACITY TO EVOLVE AND IS NOT CAPABLE OF INVENTING NOVEL FUNCTION. IN CONTRAST THE POLYMERASE ENZYME SUPPORTS MUCH HIGHER INFORMATION CONTENT AMONG THE RNAS BEING REPLICATED. IT IS ALREADY CAPABLE OF SYNTHESIZING COMPLEX FUNCTIONAL RNAS WITH GOOD FIDELITY AND ITS CAPABILITIES WILL BE ENHANCED THROUGH FURTHER OPTIMIZATION. ULTIMATELY WHEN THE ENZYME HAS THE ABILITY TO GENERATE COPIES OF ITSELF THE SYSTEM WILL BECOME SELF-OPTIMIZING BOTH FOR WHAT IT EVOLVES AND FOR ITS CAPACITY TO EVOLVE. IT HAS THE POTENTIAL TO CAPTURE THE DEFINING FEATURE OF LIFE AND TO PROVIDE THE FIRST EXAMPLE OF A LIVING SYSTEM OUTSIDE OF TERRESTRIAL BIOLOGY.$924,030
· FY2020 · National Aeronautics and Space Administration
DEFINING THE ROLE OF AUTOPHAGY KINASE ULK1 SIGNALING IN THERAPEUTIC RESPONSE OF TUBEROUS SCLEROSIS COMPLEX TO MTOR INHIBITORS$816,000
· FY2013 · Department of Defense
DOWNLOADING THE MATRIX: COMPOSING, TRANSCRIBING AND CONDUCTING A NEURAL SYMPHONY$798,463
· FY2025 · Department of the Air Force
DISCOVERY AND CHARACTERIZATION OF FUNCTIONAL BREAST CANCER MICROPROTEINS$721,500
· FY2018 · Department of the Army
CHARACTERIZATION OF RACK7 AS A NOVEL FACTOR INVOLVED IN BRCA1 MUTATION MEDIATED BREAST$695,203
· FY2010 · Department of the Army
USE OF A NOVEL EMBRYONIC MAMMARY STEM CELL GENE SIGNATURE TO IMPROVE HUMAN BREAST CANCER DIAGNOSTICS AND THERAPEUTIC DECISION MAKING$673,874
· FY2012 · Department of Defense
GENETIC THERAPY SOLUTION FOR DUCHENNE MUSCULAR DYSTROPHY$673,400
· FY2020 · Department of the Army
**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** ABOUT 80% OF ALL LAND PLANTS FORM TIGHT INTERACTIONS WITH BENEFICIAL GLOMEROMYCOTINA SOIL FUNGI. THIS SYMBIOSIS IS CALLED ARBUSCULAR MYCORRHIZAL (AM) SYMBIOSIS. AM FUNGI PROVIDE MANY BENEFITS TO THEIR PLANT HOST, FOR EXAMPLE INCREASED RESISTANCE TO PATHOGENS AND IMPROVED ACQUISITION OF ESSENTIAL MACRONUTRIENTS SUCH AS PHOSPHATE. MAJOR CROPS SUCH AS SOYBEAN, CORN, OR RICE ENGAGE IN AM SYMBIOSIS WITH SOIL FUNGI. THUS, AN EFFICIENT USE OF THESE MICROBES IN AGRICULTURE COULD DIMINISH THE NEED FOR CHEMICAL FERTILIZERS, WHICH ARE A FINITE RESOURCE AND HAVE SEVERE NEGATIVE IMPACTS ON OUR ENVIRONMENT. BECAUSE OF THEIR BENEFICIAL EFFECTS ON PLANT HEALTH AND NUTRITION, AM FUNGI ARE COMMONLY SOLD AS 'BIOFERTILIZERS'. HOWEVER, NOT ALL AM FUNGAL SPECIES ARE EQUALLY BENEFICIAL FOR A GIVEN PLANT, AND WHILE WE KNOW THAT PLANTS CAN DISTINGUISH BETWEEN DIFFERENT AM FUNGAL COLONIZERS AND PREFERENTIALLY INTERACT WITH THE ONES THAT PROVIDE THE MOST BENEFITS, THE GENETIC MECHANISM UNDERLYING THIS 'HOST-SYMBIONT PREFERENCE' IS UNKNOWN. MOST AGRO-ECOSYSTEMS ALREADY CONTAIN NUMEROUS NATIVE AM FUNGAL SPECIES AND INTRODUCING 'BIOFERTILIZER' AM FUNGI WILL RESULT IN COMPETITION OF NATIVE AND INTRODUCED AM FUNGI, MAKING THE OVERALL IMPACT OF THE SYMBIOSIS UNPREDICTABLE. IN ORDER TO EFFICIENTLY UTILIZE AM FUNGI IN A FUTURE SUSTAINABLE AGRICULTURE, WE MUST FIRST GAIN A DETAILED UNDERSTANDING HOW PLANTS DISCRIMINATE BETWEEN DIFFERENT COLONIZERS AND PROMOTE SYMBIOSIS ONLY WITH THE MOST BENEFICIAL ONES.AM FUNGI ENTER THE INNER TISSUES OF PLANT ROOTS AND AT THE SAME TIME FORM A DENSE NETWORK OF FUNGAL FILAMENTS SURROUNDING THE PLANT ROOT. THE SURROUNDING FILAMENTS TAKE UP PHOSPHATE FROM DISTANT AREAS IN THE SOIL THAT CANNOT BE REACHED BY THE ROOTS. IN THE INNER TISSUES OF THE ROOT, THE FUNGUS THEN TRADES THESE NUTRIENTS TO THE HOST PLANT IN EXCHANGE FOR CARBON IN THE FORM OF SUGARS OR FATTY ACIDS. THE PLANT TIGHTLY CONTROLS ROOT COLONIZATION BY AM FUNGI TO ENSURE THAT ONLY FUNGI THAT PROVIDE SUFFICIENT PHOSPHATE RECEIVE CARBON. USING THE MODEL LEGUME MEDICAGO TRUNCATULA (BARREL MEDIC), WE PREVIOUSLY CHARACTERIZED A SYSTEMIC SIGNALING PATHWAY INVOLVING A MOBILE PEPTIDE HORMONE (CLE53) AND ITS RECEPTOR (SUNN). THE PEPTIDE HORMONE IS PRODUCED IN COLONIZED ROOTS AND ALLOWS THE PLANT TO 'QUANTIFY' EXISTING SYMBIOSES IN ITS ROOT SYSTEM. CLE53 AND ITS RECEPTOR SUNN THEN RESTRICT FURTHER AM FUNGAL ROOT COLONIZATION ONCE A CERTAIN COLONIZATION THRESHOLD IS REACHED (QUANTITATIVE SYMBIOSIS CONTROL). IT IS HYPOTHESIZED THAT THE CLE53-SUNN SIGNALING PATHWAY PREVENTS ROOT OVER-COLONIZATION AND OVER-SEQUESTRATION OF CARBON BY THE FUNGAL SYMBIONT.BASED ON PRELIMINARY DATA, WE HYPOTHESIZE THAT THE CLE53-SUNN MODULE IS ALSO INVOLVED IN QUALITATIVE SYMBIOSIS CONTROL (I.E., SELECTION OF THE MOST BENEFICIAL SYMBIONT). WE WILL USE A COMBINATION OF MOLECULAR BIOLOGY, MOLECULAR GENETICS, TRANSCRIPTOME SEQUENCING, AND MICROSCOPY TO CHARACTERIZE THE GENETIC BASIS OF HOST-SYMB,IONT PREFERENCE IN THE MODEL LEGUME MEDICAGO TRUNCATULA. USING MUTANTS IMPAIRED IN QUANTITATIVE SYMBIOSIS CONTROL, WE WILL FIRST ASSESS THE PHYSIOLOGICAL IMPLICATIONS ON PLANT GROWTH AND PRODUCTIVITY WHEN SUCH PLANTS ARE INOCULATED WITH LOW- OR HIGH-BENEFIT AM FUNGI. WE HYPOTHESIZE THAT OVER-COLONIZATION OF THE ROOT SYSTEM BY A LOW-BENEFIT FUNGUS WILL RESULT IN OVER-SEQUESTRATION OF CARBON AND THUS NEGATIVELY IMPACT PLANT GROWTH, WHILE OVER-COLONIZATION BY A HIGH-BENEFIT FUNGUS MAY POTENTIALLY BE BENEFICIAL FOR THE PLANT. WE WILL THEN DETERMINE IF THE KNOWN REGULATORS OF QUANTITATIVE SYMBIOSIS CONTROL (CLE53 AND SUNN) ARE ALSO INVOLVED IN QUALITATIVE SYMBIOSIS CONTROL, I.E. IF THE CLE53-SUNN MODULE RESPONDS DIFFERENTLY TO AM FUNGI CONFERRING LOW OR HIGH DEGREES OF BENEFITS (PHOSPHATE) TO THE PLANTS. USING A YEAST-1-HYBRID SCREEN TO DETECT INTERACTIONS OF DNA AND PROTEINS SUCH AS TRANSCRIPTIONAL REGULATORS, WE WILL IDENTIFY SPECIFIC REGULATORY PROTEINS INVOLVED IN THE REGULATION OF CLE53 EXPRESSION. LASTLY, WE WILL DEVELOP NEW MICROSCOPIC TOOLS THAT WILL ALLOW US TO SIMULTANEOUSLY IMAGE TWO DIFFERENT AM FUNGAL SPECIES COLONIZING THE SAME ROOT SYSTEM AND USE THESE TOOLS TO INVESTIGATE IF THE CLE53-SUNN MODULE IS INVOLVED IN HOST-SYMBIONT PREFERENCE. IN ADDITION, WE WILL PERFORM TRANSCRIPTOME SEQUENCING OF MEDICAGO TRUNCATULA ROOT SYSTEMS INOCULATED WITH HIGH- AND/OR LOW-BENEFIT AM FUNGI TO IDENTIFY YET UNKNOWN ADDITIONAL REGULATORS OF HOST-SYMBIONT PREFERENCE.TO DATE, VIRTUALLY NOTHING IS KNOWN ABOUT THE GENETIC BASIS OF PLANT RESPONSES TO SIMULTANEOUS COLONIZATION BY HIGH- AND LOW-BENEFIT AM FUNGI. THIS PROJECT WILL MAKE AN IMPORTANT CONTRIBUTION TO FILL THIS KNOWLEDGE GAP. FURTHERMORE, UNDERSTANDING HOST-SYMBIONT PREFERENCE ON A GENETIC LEVEL IS AN IMPORTANT PREREQUISITE TO DEVELOP PLANT LINES WITH INCREASED MYCORRHIZAL CAPACITIES AND OPTIMIZED ABILITIES TO SELECT FOR THE BEST SYMBIONT IN AGRO-ECOSYSTEMS WHERE MULTIPLE AM FUNGAL SPECIES ARE PRESENT. THE PROJECT WILL IDENTIFY SEVERAL POTENTIAL TARGETS FOR FUTURE CROP IMPROVEMENT, INCLUDING THE PREVIOUSLY DESCRIBED GENES CLE53 AND SUNN, THE TRANSCRIPTIONAL REGULATORS TO BE IDENTIFIED IN THE YEAST-1-HYBRID SCREEN, AND NOVEL REGULATORS TO BE IDENTIFIED IN THE TRANSCRIPTOME SEQUENCING EXPERIMENT. THIS PROJECT WILL LAY THE GROUNDWORK FOR FUTURE BREEDING EFFORTS TO MAXIMIZE SYMBIOTIC CAPACITIES OF CROP PLANTS AND WILL SIGNIFICANTLY CONTRIBUTE TO OUR PATH TOWARDS SUSTAINABLE AGRICULTURE.$631,572
· FY2024 · National Institute of Food and Agriculture
TARGETING MUTATIONAL DRIVERS IN IPMN USING LIPID NANOPARTICLE DELIVERY SYSTEMS$588,507
· FY2022 · Defense Health Agency