CHARACTERIZING AGE-RELATED DECLINE OF NEURAL CIRCUITS BY SINGLE-CELL PROFILING - PROJECT SUMMARY/ABSTRACT T…

Assistance award details

Assistance award identifier

ASST_NON_R00AG062746_075

FAIN

R00AG062746

Recipient

BAYLOR COLLEGE OF MEDICINE

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$996,000

Period

Apr 1, 2019 – Jan 31, 2024

Fiscal year

2021

Place of performance state

TX

Source file

FY2021_All_Assistance_Full_20261006.zip

Description

CHARACTERIZING AGE-RELATED DECLINE OF NEURAL CIRCUITS BY SINGLE-CELL PROFILING - PROJECT SUMMARY/ABSTRACT THE FUNCTION OF THE NERVES SYSTEM RELIES ON APPROPRIATE NEURAL CIRCUIT ASSEMBLY AND LONG-TERM MAINTENANCE OF THE CIRCUIT INTEGRITY. EMPLOYING INTEGRATED SINGLE-CELL GENOMIC APPROACHES, HERE I PROPOSE TO INVESTIGATE CELLULAR AND MOLECULAR MECHANISMS OF DEVELOPMENTAL ASSEMBLY AND AGE-INDUCED DECLINE OF NEURAL CIRCUITS USING THE DROSOPHILA OLFACTORY SYSTEM. IN THE DROSOPHILA OLFACTORY CIRCUIT, 50 CLASSES OF OLFACTORY RECEPTOR NEURONS (ORNS; EACH CLASS EXPRESSES A UNIQUE OLFACTORY RECEPTOR) CONNECT PRECISELY WITH 50 CLASSES OF OLFACTORY PROJECTION NEURONS, PROVIDING A POWERFUL MODEL TO STUDY THE NEURONAL WIRING SPECIFICITY. SINGLE-CELL PROFILING METHODS (RNA-SEQ AND ATAC-SEQ) ARE EMERGING AS POWERFUL APPROACHES TO STUDY NUMEROUS BIOLOGICAL QUESTIONS, INCLUDING NEURODEVELOPMENT [22-27]. RECENTLY, I HAVE DEVELOPED THE FIRST SINGLE-CELL RNA-SEQ PROTOCOL FOR DROSOPHILA NEURONS (LI ET AL., 2017 CELL) [25]. HERE, I WOULD LIKE TO APPLY SINGLE-CELL PROFILING APPROACHES TO 1) CLASSIFY ORN CLASSES, 2) IDENTIFY WIRING SPECIFICITY GENES, AND 3) EXPLORE MECHANISMS THAT COORDINATE OLFACTORY RECEPTOR EXPRESSION AND ORN WIRING SPECIFICITY (AIMS 1&2; MAINLY ON K99 TRAINING PHASE). LOSS OF OLFACTORY SENSITIVITY IS AMONG THE FIRST SIGNS OF AGING AND NEURODEGENERATIVE DISEASES, SUCH AS ALZHEIMER'S. IN DROSOPHILA, THE OLFACTORY SENSITIVITY ALSO SIGNIFICANTLY DECLINES WITH AGE. HERE, I PROPOSE A MECHANISTIC STUDY TO IDENTIFY CELLULAR AND MOLECULAR MECHANISMS FOR AGE-RELATED OLFACTORY DECLINE IN DROSOPHILA. OUR LAB HAS RECENTLY FOUND THAT GLIA CELLS ARE CRITICAL FOR REGULATING THE ASSEMBLY OF THE FLY OLFACTORY CIRCUIT [8]. NUMEROUS STUDIES HAVE SHOWN THAT THE GLIA-NEURON INTERACTIONS ARE IMPORTANT FOR THE BRAIN FUNCTION IN MANY NEURONAL SYSTEMS [9-11]. TOGETHER, I HYPOTHESIZE THAT GLIAL CELLS CONTINUE TO BE REQUIRED FOR MAINTAINING THE OLFACTORY CIRCUIT FUNCTION THROUGHOUT THE LIFE, AND