MORE THAN JUST A LOAD CONTROL: CYTOSKELETAL FORM AND FUNCTION DURING AGING - PROJECT SUMMARY. ALTHOUGH THE…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG065200_075
- FAIN
- R00AG065200
- Recipient
- UNIVERSITY OF SOUTHERN CALIFORNIA
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $681,059
- Period
- May 1, 2020 – May 31, 2024
- Fiscal year
- 2021
- Place of performance state
- CA
- Source file
- FY2021_All_Assistance_Full_20261006.zip
Description
MORE THAN JUST A LOAD CONTROL: CYTOSKELETAL FORM AND FUNCTION DURING AGING - PROJECT SUMMARY. ALTHOUGH THE CYTOSKELETON HAS HISTORICALLY BEEN UNDERSTOOD AS THE STRUCTURAL FRAMEWORK OF THE CELL, THE PROPER FUNCTION OF ACTIN IS ALSO REQUIRED FOR A DIVERSE ARRAY OF CELLULAR PATHWAYS. THE COLLAPSE OF THESE CELLULAR PROCESSES MANIFESTS DURING AGING AND EXPOSURE TO A MYRIAD OF STRESSES, WHICH IS IN PART DUE TO THE BREAKDOWN OF THE CYTOSKELETON UNDER THESE CONDITIONS. INTERESTINGLY, THE BREAKDOWN OF THE CYTOSKELETON THROUGHOUT AGE HAS BEEN ADOPTED AS COMMON KNOWLEDGE IN THE FIELD OF AGING BIOLOGY, DESPITE THE LACK OF CLEAR AND DIRECT EVIDENCE. A MAJOR CONTRIBUTOR TO THE LACK OF THESE ESSENTIAL STUDIES IS THE LACK OF TOOLS AVAILABLE FOR IN VIVO, LIVE-CELL IMAGING OF THE ACTIN CYTOSKELETON IN MULTI-CELLULAR ORGANISMS. EARLY IN MY POSTDOCTORAL CAREER, I DEVELOPED A SYSTEM FOR ROBUST, TISSUE-SPECIFIC, LIVE-CELL IMAGING OF THE CYTOSKELETON IN THE MUSCLE, INTESTINE, AND HYPODERMIS OF C. ELEGANS, UTILIZING LIFEACT FUSED TO A FLUORESCENT MOLECULE. LIFEACT-MRUBY RELIABLY BINDS TO F-ACTIN, ALLOWING VISUALIZATION OF FUNCTIONAL, FILAMENTOUS ACTIN IN THE CELLS IT IS EXPRESSED. USING THIS SYSTEM, I PERFORMED AN EXHAUSTIVE CHARACTERIZATION OF THE DECLINE OF ACTIN CYTOSKELETAL INTEGRITY DURING AGING. THIS WORK LAID THE FOUNDATION OF MY CURRENTLY ONGOING WORK IN IDENTIFICATION OF NOVEL REGULATORS OF THE ACTIN CYTOSKELETON. HAVING SET UP A SYSTEM TO INTERROGATE CYTOSKELETAL QUALITY, I CAN NOW INTERROGATE NOVEL GENES IN THEIR POTENTIAL ROLE FOR ACTIN REGULATION. USING THIS AND OTHER PLATFORMS, I PERFORMED A MULTI-PRONGED SCREENING APPROACH TO IDENTIFY NOVEL GENETIC REGULATORS OF ACTIN. THESE STUDIES COMBINED IN VIVO LIVE CELL IMAGING OF ACTIN FILAMENTS, SYNTHETIC LETHALITY SCREENING WITH KNOWN REGULATORS OF THE ACTIN CYTOSKELETON, AND BOTH TRANSCRIPTOME ANALYSIS AND WHOLE GENOME CRISPR-CAS9 SCREENING OF ORGANISMS EXPERIENCING ACTIN STRESS. CROSS-REFERENCING THESE RICH DATASETS HAS REVEALED