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A scalable mass spectrometry platform for proteome mapping of brain tissues

Award Number: RF1MH128885
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2021
PERIOD OF PERFORMANCE END DATE: 09/14/2025

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A scalable mass spectrometry platform for proteome mapping of brain tissues - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$9,567 )
2026	2021	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Mental Health Research Grants	000	1	2/4/2026	NEW	-$9,567
														Subtotal = -$9,567

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2021	BATTELLE MEMORIAL INSTITUTE	902 BATTELLE BLVD	RICHLAND	WA	99354	BENTON	USA	Mental Health Research Grants	000	1	8/19/2024	NEW	$0
														Subtotal = $0

Issue Date FY: 2021 ( Subtotal = $3,673,687 )
2021	2021	BATTELLE MEMORIAL INSTITUTE	900 BATTELLE BLVD	RICHLAND	WA	99352	BENTON	USA	Mental Health Research Grants	000	1	9/10/2021	NEW	$3,673,687
														Subtotal = $3,673,687

Grand Total All Awards = $3,664,120

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A scalable mass spectrometry platform for proteome mapping of brain tissues

Award Number: RF1MH128885

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2021

PERIOD OF PERFORMANCE END DATE: 09/14/2025

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