# The crosstalk of organelles involved in autophagosome biogenesis

> **NIH NIH R35** · UNIVERSITY OF CINCINNATI · 2024 · $405,000

## Abstract

PROJECT SUMMARY
Autophagy is a crucial catabolic pathway by which cellular waste is recycled. Autophagic dysfunction has
been implicated in cellular quality control, responses to stress, development, lifespan, and a range of
infectious and other diseases in humans, including cancer, neurodegenerative diseases, and diabetes. The
crosstalk of organelles including fusion and contact is a critical process involved in autophagosome
biogenesis. The exact molecular mechanism for the crosstalk of organelles in autophagy remains far from
clear and thus a major topic of investigation. Since organelle crosstalk could act as a switch to spatially and
temporally regulate the autophagic flux in human diseases due to its dysregulation, dissecting and
controlling the regulatory machinery is essential to understanding the exact roles of autophagy in specific
disease contexts. Therefore, studying the molecular mechanism of organelle crosstalk will provide the
opportunity to develop new therapeutic strategies in order to control activity of autophagy. We have
developed in vitro protein reconstitution systems and live cell super-resolution imaging assays to study the
dynamics and interactions of organelles. In this R35 renewal application, based on our preliminary data, we
hypothesize that the crosstalk of organelles including fusion and contact regulates autophagosome
biogenesis, in which SNAREs, vacuolar protein sorting-associated protein 33A (VPS33A), and Atg9 play a
critical role. In the next five years, we will 1) study v- and t- SNAREs and accessory proteins involved in
autophagosome maturation; 2) elucidate the role of Atg9 vesicle contact resulting in clustering for early
autophagosome biogenesis; 3) analyze and control the crosstalk between Atg9 vesicles and other
organelles. Systematical studies on the role of organelle fusion and contact in autophagosome biogenesis
through multiple biochemical, biophysical, and cell biological approaches are critical to elucidate detailed
molecular mechanisms, which could offer therapeutic advances. Moreover, an attempt to control organelle
dynamics and interactions by optogenetic tools would be an important expansion, which is also essential for
future drug development.

## Key facts

- **NIH application ID:** 10841074
- **Project number:** 2R35GM128837-06
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Jiajie Diao
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $405,000
- **Award type:** 2
- **Project period:** 2018-08-01 → 2029-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10841074

## Citation

> US National Institutes of Health, RePORTER application 10841074, The crosstalk of organelles involved in autophagosome biogenesis (2R35GM128837-06). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10841074. Licensed CC0.

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