# A scalable mass spectrometry platform for proteome mapping of brain tissues

> **NIH NIH RF1** · BATTELLE PACIFIC NORTHWEST LABORATORIES · 2021 · $3,673,687

## Abstract

ABSTRACT
The brain is the most complex organ in the mammalian body. Bulk analysis obscures heterogeneity of cell
types present even in the smallest brain regions. Multi-omics single-cell resolution 3D-characterization of brain
tissue is critically important to create comprehensive brain cell censuses and altas. Recent technological
advances allow for single-cell transcriptome mapping of mammalian brains, but single-cell proteomics
technologies are lagging far behind transcriptomics technologies. The lack of high-resolution proteome
characterization of brain tissues in the BICCN consortium represents a significant knowledge gap between
protein and mRNA for achieving a more complete understanding of how diverse brain cells are organized into
distinct anatomical and functional regions. The objective of this application is to address this gap by developing
a robust scalable mass spectrometry (MS) platform for high-resolution 3D-proteome mapping of brain tissues.
The feasibility is strongly supported by our recent progress in technology development and our experiences in
proteome mapping of mouse tissues. Aim 1 will focus on the development of a robust scalable MS platform
through 1) further improving sample preparation for rapid effective processing of single cells and small tissue
voxels, and 2) leveraging multiple disruptive technologies developed at our group for significantly improving
detection sensitivity and sample throughput. The new platform is expected to allow for reliable quantification
of >3,000 proteins in single cells and >6500 proteins in 100 cells with ~500 samples per day. Aim 2 will
optimize and demonstrate the scalable MS platform for 2D-proteome mapping of mouse MOp and human M1
when combined with laser capture microdissection for tissue voxels. Aim 3 will apply the new platform for
3D-proteome mapping of MOp/M1 within the BICCN consortium and integrate proteomic data with existing
transcriptomic data for proteogenomic analysis. We envision that the new platform will become a convenient
indispensable tool for high-resolution 3D-proteome mapping of brain tissues in the BICCN consortium and
extend the BICCN toolbox. In turn, it could make substantial contributions to improve our understanding of
brain function in health and disease.

## Key facts

- **NIH application ID:** 10370198
- **Project number:** 1RF1MH128885-01
- **Recipient organization:** BATTELLE PACIFIC NORTHWEST LABORATORIES
- **Principal Investigator:** Tujin Shi
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $3,673,687
- **Award type:** 1
- **Project period:** 2021-09-15 → 2025-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10370198

## Citation

> US National Institutes of Health, RePORTER application 10370198, A scalable mass spectrometry platform for proteome mapping of brain tissues (1RF1MH128885-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10370198. Licensed CC0.

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