UNDERSTANDING THE MOLECULAR MECHANISM OF MEMORY FROM SINGLE-CELL GENE EXPRESSION TO PROTEIN FOLDING - PROJE…

Assistance award details

Assistance award identifier

ASST_NON_R00AG068306_075

FAIN

R00AG068306

Recipient

THE UNIVERSITY OF IOWA

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$742,019

Period

Apr 15, 2021 – Jul 31, 2026

Fiscal year

2023

Place of performance state

IA

Source file

FY2023_All_Assistance_Full_20261006.zip

Description

UNDERSTANDING THE MOLECULAR MECHANISM OF MEMORY FROM SINGLE-CELL GENE EXPRESSION TO PROTEIN FOLDING - PROJECT SUMMARY / ABSTRACT DEFICITS IN COGNITIVE FUNCTION AND MEMORY ARE A DEBILITATING ASPECT OF NEURODEGENERATIVE DISEASE RESULTING IN LONG-TERM DISABILITY, ENORMOUS SUFFERING TO INDIVIDUALS AND THEIR FAMILIES, AND SIGNIFICANT SOCIOECONOMIC COST. CURRENTLY, MORE THAN 16 MILLION AMERICANS LIVE WITH COGNITIVE IMPAIRMENT, AND THIS NUMBER IS EXPECTED TO CONTINUE RISING AS THE NUMBER OF INDIVIDUALS AFFECTED BY ALZHEIMER'S DISEASE AND RELATED DEMENTIAS IS PREDICTED TO DOUBLE BY 2060. LONG-TERM MEMORY CONSOLIDATION REQUIRES THE INDUCTION OF GENE EXPRESSION IN A SPECIFIC TEMPORAL PATTERN. NEWLY SYNTHESIZED TRANSCRIPTS ARE TRANSLATED AND FOLDED INTO FUNCTIONAL PROTEINS AND THEN TRAFFICKED TO THE CORRECT CELLULAR LOCATION. DYSFUNCTION IN ANY OF THESE STEPS CAN LEAD TO MEMORY IMPAIRMENT AND MAY BE DYSREGULATED IN DISEASE CONDITIONS, ALTHOUGH THE PRECISE MECHANISMS BY WHICH THIS OCCURS ARE UNCLEAR. MY LONG- TERM GOAL IS TO DETERMINE THE SPECIFIC MOLECULAR MECHANISMS THROUGH WHICH THE NR4A SUB-FAMILY REGULATES GENE EXPRESSION TO CONTROL LONG-TERM MEMORY IN ORDER TO DEVELOP THERAPEUTIC TOOLS TO TREAT AD, WHICH I WILL PURSUE AS AN INDEPENDENT INVESTIGATOR AT A RESEARCH-FOCUSED INSTITUTION. THE OVERALL OBJECTIVE OF THIS PROPOSAL IS TO DETERMINE THE MECHANISMS THAT LINK TRANSCRIPTIONAL REGULATION AND PROTEIN FOLDING DURING MEMORY FORMATION AND HOW THE DISRUPTION OF THESE PROCESSES CONTRIBUTES TO COGNITIVE IMPAIRMENT IN ALZHEIMER'S DISEASE. MY CENTRAL HYPOTHESIS IS THAT NR4A REGULATES GENES IN SPECIFIC CELL TYPES TO FACILITATE PROTEIN FOLDING AND MEMORY FORMATION. I WILL TEST THIS THROUGH THE FOLLOWING THREE AIMS: SPECIFIC AIM 1 (K99): IDENTIFY CELL-TYPE SPECIFIC TRANSCRIPTIONAL SIGNATURES OF MEMORY AND IDENTIFY DIRECT GENE TARGETS OF NR4A DURING MEMORY CONSOLIDATION USING A SINGLE-CELL RNA SEQUENCING APPROACH; SPECIFIC AIM 2 (K99): DETERMINE THE ROLE OF AN NR4A TARGET, THE PROTEIN