REGULATORY MECHANISMS OF RARE NON-CODING VARIATION IN NEURODEGENERATION-ASSOCIATED LOCI - ABSTRACT THE GOAL…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG068271_075
- FAIN
- R00AG068271
- Recipient
- HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $725,472
- Period
- Sep 1, 2021 – Aug 31, 2024
- Fiscal year
- 2021
- Place of performance state
- AL
- Source file
- FY2021_All_Assistance_Full_20261006.zip
Description
REGULATORY MECHANISMS OF RARE NON-CODING VARIATION IN NEURODEGENERATION-ASSOCIATED LOCI - ABSTRACT THE GOAL OF THIS NIH PATHWAY TO INDEPENDENCE AWARD IS TO PROVIDE DR. J. NICHOLAS (NICK) COCHRAN WITH A COMPREHENSIVE TRAINING PROGRAM TO PREPARE HIM TO BE A LEADING INDEPENDENT INVESTIGATOR WHO USES GENOMIC APPROACHES TO STUDY NEURODEGENERATIVE DISEASE. WE PROPOSE ONE YEAR OF TRAINING IN FUNCTIONAL GENOMICS, ADVANCED STATISTICS, AND ADVANCED DATA SCIENCE TO COMPLEMENT OVER TEN YEARS OF TRAINING THAT DR. COCHRAN HAS RECEIVED TO DATE IN NEUROSCIENCE AND GENOMICS. GENOME SEQUENCING STUDIES CONTINUE TO PROVIDE NEW STATISTICAL ASSOCIATIONS WITH DISEASE, BUT TO DATE NON-CODING VARIATION HAS BEEN LARGELY DISREGARDED. A CRITICAL BARRIER TO INCORPORATING RARE NON-CODING VARIATION INTO BURDEN ANALYSES AND TO FURTHER STUDYING THE EFFECTS OF THOSE VARIANTS ON TRANSCRIPTIONAL COMPLEXES OR DISEASE-RELATED CELL BIOLOGY HAS HISTORICALLY BEEN A LACK OF AN ABILITY TO PROPERLY CATEGORIZE THE EFFECT OF NON-CODING VARIANTS AND ESTABLISH THEM AS DISEASE-ASSOCIATED. THE PI HAS PUT FORWARD ONE APPROACH TO ADDRESS THIS BARRIER USING COMPUTATIONAL FILTERING IN A RECENT STUDY, AND THE AIMS HERE WILL ALLOW FOR FURTHER MECHANISTIC REFINEMENT OF APPROACHES TO ASSESS THE FUNCTIONAL CONSEQUENCES OF RARE NON-CODING VARIATION FOR NEURODEGENERATIVE DISEASES. IN ADDITION TO ALLOWING FOR DISCOVERY OF MORE GENE- DISEASE ASSOCIATIONS, THE LOCATION OF DISEASE-ASSOCIATED NON-CODING VARIANTS WILL INFORM ON THE BIOLOGY OF HOW THE TARGET GENES ARE REGULATED (RESULTANTLY PROVIDING INSIGHT INTO DISEASE ETIOLOGY), AND COULD EVEN PROVIDE SUPPORT FOR NEW THERAPEUTIC AVENUES FOR CONSIDERATION BY PROVIDING EVIDENCE FOR THE THREE DIMENSIONAL PROTEIN COMPLEXES CONTROLLING EXPRESSION OF DISEASE ASSOCIATED GENES, WHICH, IF UNDERSTOOD WELL ENOUGH, MAY BE DRUGGABLE. THIS WOULD HAVE BROAD APPLICABILITY FOR ANY GENE-DISEASE ASSOCIATION. HOWEVER, GIVEN THE FOCUS OF THIS PROPOSAL, THE PI SPECIFICALLY PROPOSES (1) EXPERIMENTS TO