# Spatial and temporal regulation of nutrient sensing

> **NIH NIH R35** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2022 · $335,000

## Abstract

Project Summary / Abstract
 Cells need to sense the nutrient availability to adjust their survival strategy. In eukaryotic cells, the
mechanistic Target of Rapamycin Complex 1 (mTORC1) is a key regulator of cell growth and proliferation.
Upon activation in a nutrient-rich environment, mTORC1 triggers anabolic reactions and inhibits catabolism.
Amino acid signals are transmitted to mTORC1 through a series of protein complexes that ultimately converge
on the Rag GTPases, a heterodimeric GTPase that recruits mTORC1 to the lysosomal surface. However, the
molecular mechanisms of how these protein complexes dynamically transmit the amino acid signal are still
elusive. In this proposal, we aim to develop biophysical tools to study the dynamics of the amino acid sensing
process. Specifically, we aim to use single molecule FRET to study the conformational dynamics of the Rag
GTPase heterodimer and its regulators (Project 1). Further, we plan to reconstitute an in vitro system to
recapitulate Rag-dependent amino acid sensing on a membrane surface (Project 2), and use cryo-electron
tomography (cryo-ET) to visualize the signaling complexes in their native environment (Project 3). The
outcomes will yield novel insights into this important biological process and provide guidance to the
development of therapeutic strategies.

## Key facts

- **NIH application ID:** 10498962
- **Project number:** 1R35GM146824-01
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Kuang Shen
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $335,000
- **Award type:** 1
- **Project period:** 2022-08-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10498962

## Citation

> US National Institutes of Health, RePORTER application 10498962, Spatial and temporal regulation of nutrient sensing (1R35GM146824-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10498962. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*