# Dissecting the Molecular Mechanisms of Selective Autophagy

> **NIH NIH R35** · DARTMOUTH COLLEGE · 2021 · $405,000

## Abstract

The accumulation of damaged organelles and large protein aggregates has been correlated
with human diseases including cancer and neurodegeneration. Due to the large and complex
nature of these cytosolic components, they must be degraded through a specialized vesicle
trafficking pathway termed selective autophagy. In selective autophagy, large cytosolic material
is captured within double membrane vesicles, termed autophagosomes, and targeted to the
vacuole or lysosome for degradation. While the biogenesis of most trafficking vesicles occurs
through the budding of a preexisting membrane surface, the biogenesis of the selective
autophagosome occurs through a distinct process in which the cargo serves as a template for
de novo vesicle biogenesis. The molecular mechanisms of these vesicle biogenesis events are
largely unknown. The primary reason for this gap in our knowledge is that the structure and
function of the proteins which function early in selective autophagy are unknown. In addition,
many of these proteins lack obvious conserved domains which makes it challenging to predict a
mechanism for these proteins. To investigate the structure and function of these proteins we will
use hybrid structural biology methods, yeast genetics, biochemistry and cell biology. To
complement our structure and function studies we will develop a method to reconstitute
selective autophagy. This reconstitution system will ultimately enable us to evaluate what
selective autophagy factors are required at each stage of vesicle biogenesis. Through these
diverse investigations, we will establish a comprehensive description of the molecular
mechanisms of selective autophagy. As selective autophagy has been increasingly correlated
with human diseases, determining the mechanisms of selective autophagy will also provide
invaluable insight into the complicated relationship between selective autophagy and human
disease.

## Key facts

- **NIH application ID:** 10246865
- **Project number:** 5R35GM128663-04
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Michael Joseph Ragusa
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246865

## Citation

> US National Institutes of Health, RePORTER application 10246865, Dissecting the Molecular Mechanisms of Selective Autophagy (5R35GM128663-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10246865. Licensed CC0.

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