# Localized Real-time Sensors for Metabolic Signaling

> **NIH NIH R35** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $381,480

## Abstract

PROJECT SUMMARY
 Metabolic pathways function in response to cellular needs, but they also can direct signaling and even
influence how our genes are read. If we can understand the underlying mechanisms of metabolic-dependent
signaling, it could broaden the range of interventions when combatting diseases to include modulation of cell
metabolism. It is currently challenging to accurately measure concentrations and fluctuations of the metabolic
intermediates that participate in these signaling pathways. By understanding the intracellular concentrations
and regulation of these signaling metabolites, we can determine how the availability of a specific metabolite is
poised to impact enzymatic activity, as well as the extent and timing that their levels may fluctuate over the
course of physiology and disease. These metabolites are highly compartmentalized even within individual
cells, and an accurate measurement for signaling needs to distinguish its free concentration from bound pools.
Moreover, signaling metabolites often have distinct roles in different parts of the cells and their concentrations
can be differentially regulated. We are deconvoluting the signaling roles of metabolites by developing small
single-fluorescent protein biosensors that are genetically encoded and selective for specific intracellular
metabolites. These sensors can be localized subcellularly and measured changes in their fluorescence reflect
changes in concentration for specific intermediary metabolites. Together the data will determine how that
metabolite regulates signaling. In this proposal, we use mitochondrial NAD+ sensors to elucidate the
mechanisms of transport for human mitochondrial carrier family member, SLC25A51, and determine its roles in
disease. We also develop new sensors to expand our investigations to additional signaling metabolites,
including NAD-derived metabolites.

## Key facts

- **NIH application ID:** 10764520
- **Project number:** 1R35GM152218-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Xiaolu Ang Cambronne
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $381,480
- **Award type:** 1
- **Project period:** 2024-09-01 → 2029-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764520

## Citation

> US National Institutes of Health, RePORTER application 10764520, Localized Real-time Sensors for Metabolic Signaling (1R35GM152218-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10764520. Licensed CC0.

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