RF1MH128885
Project Grant
Overview
Grant Description
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 atlases.
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 >6,500 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.
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 atlases.
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 >6,500 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.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Richland,
Washington
993520902
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the End Date has been extended from 09/14/24 to 09/14/25.
Battelle Memorial Institute was awarded
Scalable Mass Spectrometry Platform Proteome Mapping of Brain Tissues
Project Grant RF1MH128885
worth $3,673,687
from the National Institute of Mental Health in September 2021 with work to be completed primarily in Richland Washington United States.
The grant
has a duration of 4 years and
was awarded through assistance program 93.242 Mental Health Research Grants.
The Project Grant was awarded through grant opportunity BRAIN Initiative Cell Census Network (BICCN) Scalable Technologies and Tools for Brain Cell Census (R01 Clinical Trial Not Allowed).
Status
(Ongoing)
Last Modified 9/5/24
Period of Performance
9/15/21
Start Date
9/14/25
End Date
Funding Split
$3.7M
Federal Obligation
$0.0
Non-Federal Obligation
$3.7M
Total Obligated
Activity Timeline
Transaction History
Modifications to RF1MH128885
Additional Detail
Award ID FAIN
RF1MH128885
SAI Number
RF1MH128885-3176823852
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Nonprofit With 501(c)(3) IRS Status (Other Than An Institution Of Higher Education)
Awarding Office
75N700 NIH NATIONAL INSTITUTE OF MENTAL HEALTH
Funding Office
75N700 NIH NATIONAL INSTITUTE OF MENTAL HEALTH
Awardee UEI
CWKJEXDG79A7
Awardee CAGE
1A453
Performance District
WA-04
Senators
Maria Cantwell
Patty Murray
Patty Murray
Modified: 9/5/24