# Elucidating the function of mammalian autophagy receptors in selective autophagy

> **NIH NIH R00** · DARTMOUTH COLLEGE · 2020 · $249,000

## Abstract

Project Summary / Abstract
The long-term goal of this project is to elucidate the molecular mechanism by which autophagy receptors effect
selective autophagy in both normal and disease conditions. Autophagy is a process of non-selective
cytoplasmic degradation that is required for cell survival during periods of starvation or stress (termed bulk
autophagy), as well as for the selective degradation of protein aggregates, damaged organelles, and other
large targets that otherwise accumulate and cause disease (selective autophagy). In nearly all cases, the
induction of autophagy requires the activation of a dedicated kinase, Atg1, that is conserved from yeast (Atg1)
to man (ULK1 and ULK2). Neither how ULK1/2 are activated, nor how phosphorylation of ULK1/2 substrates
enables autophagy induction is well understood. The goal of this proposal is to take an autophagy-receptor-
centric approach to understanding selective autophagy in mammalian systems. Specifically, in Aim 1, I will
biochemically characterize the role of autophagy receptors in ULK1/2 activation. I will then determine the effect
of receptor mutations associated with human disease. In Aim 2, I will use CRISPR/Cas9 technology to screen
for novel modulators of selective autophagy in mammalian cells, including screens for suppressors of disease-
associated alleles. These studies will identify potential therapeutic targets for autophagy-associated diseases.
In Aim 3, I will use a novel cell free assay for ULK1/2 activity to identify substrates of these autophagy kinases
and determine the mechanism by which ULK1/2 activation by receptors drives selective autophagy.
Collectively, my combined approaches will reveal conserved principles of autophagy induction and, ultimately,
inform our understanding of autophagy dysregulation in various disease states. During the early stage of this
award, I will gain valuable technical skills, including in mammalian tissue culture, CRISPR screening and mass
spectrometry, that will enable me to develop a unique research program. Under the mentoring of my formal
advisory committee, I will develop important soft skills, such as grant writing, presentation skills and lab
leadership. This combination of training, support and career mentoring will be instrumental in my transition to
independence as a tenure-track faculty at a leading institution.

## Key facts

- **NIH application ID:** 9864084
- **Project number:** 5R00GM117218-04
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Christopher J Shoemaker
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 5
- **Project period:** 2016-08-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864084

## Citation

> US National Institutes of Health, RePORTER application 9864084, Elucidating the function of mammalian autophagy receptors in selective autophagy (5R00GM117218-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864084. Licensed CC0.

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