# In situ proteomics for brain using genetically encoded probes.

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2022 · $237,000

## Abstract

Summary
This exploratory proposal will develop an intersectional genetics approach to in situ
proteomics in a mammalian brain based on a split biotin ligase fragments with induced
dimerization in mice. Current proteomic databases draw from high-throughput
experiments in non-physiological settings that typically involve high expression in a
highly transformed cell line or in vitro system. To develop a more physiological approach
to key protein networks for genetically complex disorders, we will adapt a split biotin
ligase approach for inducible proximity labeling in situ in mouse brain. We will tag an
endogenous protein of interest with one fragment of the split biotin ligase by germline
editing in mice and use genetic crosses to pair this fusion gene with one for the
complementary split fragment expressed from a distinct locus. Dimerization to form the
active enzyme is controlled by overlapping expression and rapamycin administration.
This will allow us to identify the protein of interest’s physical network in physiological
context. As an initial demonstration we will tag endogenous Zfp804a, whose human
cognate is encoded by a well-replicated risk locus for psychiatric illness. In parallel, we
will develop cell-based models to refine the approach, focus results on selected
subcellular compartments, and extend the approach to other neurodevelopmental risk
loci and Zfp804a partner proteins.

## Key facts

- **NIH application ID:** 10576153
- **Project number:** 1R21MH132143-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** BRUCE A HAMILTON
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $237,000
- **Award type:** 1
- **Project period:** 2022-09-20 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10576153

## Citation

> US National Institutes of Health, RePORTER application 10576153, In situ proteomics for brain using genetically encoded probes. (1R21MH132143-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10576153. Licensed CC0.

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