# Characterizing age-related decline of neural circuits by single-cell profiling

> **NIH NIH R00** · BAYLOR COLLEGE OF MEDICINE · 2022 · $249,000

## Abstract

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 that age-associated glial dysfunction contributes to the
olfactory decline in old flies. I would like to combine single-cell profiling techniques with genetic methods to test
this hypothesis (Aim 3; mainly on R00 independent phase).
 My mentoring team consists of Dr. Liqun Luo (mentor), a world-renowned neuroscientist, and Drs.
Howard Chang (co-mentor) and Stephen Quake (collaborator), two leading scientists in single-cell genomics
and epigenomics, as well as Dr. Tony Wyss-Coray (consultant), an expert on aging and neurodegeneration,
and Dr. Marc Freeman (consultant), an expert on Drosophila glia. With their guidance, I believe that I will gain
extensive training in my transition to be an independent PI.

## Key facts

- **NIH application ID:** 10333409
- **Project number:** 5R00AG062746-04
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Hongjie Li
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10333409

## Citation

> US National Institutes of Health, RePORTER application 10333409, Characterizing age-related decline of neural circuits by single-cell profiling (5R00AG062746-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10333409. Licensed CC0.

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