# Highly sensitive proteomics method to probe cell heterogeneity at single cell resolution

> **NIH NIH R35** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2022 · $394,089

## Abstract

Project Summary/Abstract:
 As the single-cell transcriptomics analysis becomes more accessible, individual cells
can now be classified individually, allowing us to understand cell heterogeneity as one of the
key driving forces in neuron development and tumor evolution. However, the presence of
mRNA is not always coupled with protein expression, single-cell proteomics will provide a more
precise view of the cell components and signaling, including key post-translational modification
events such as phosphorylation.
 Here we propose to combine several different strategies to develop a highly sensitive
proteomics method to probe cell heterogeneity at single cell resolution. Specifically, we will 1)
develop chemical labeling probes to enhance peptide ionization; 2) develop an isobaric
isotopologue labeling approach to quantify single mammalian cell from various cell lines; 3)
develop informatics tools and statistical models to resolve cell heterogeneity at single-cell
resolution with non-single-cell proteomics data. Each of these proposed methods alone, could
potentially enable us to measure the proteome of a single mammalian cell. When combined,
they will result in a highly sensitive platform that could potentially allow us to probe the
proteome at the level of a single mitochondria or bacteria.
 The long-term goal of this project is to elucidate the fundamental mechanisms of the
origin and implications of cell heterogeneity. This proposed research is highly relevant to public
health in the fields of tumor evolution, cancer metastasis, developmental neurobiology and
neurodegenerative disease. Understanding cell heterogeneity will help us to develop more
effective drug treatments to many diseases. Therefore, the proposed research is relevant to
the part of NIH's mission that fosters “fundamental creative discoveries, innovative research
strategies, and their applications as a basis for ultimately protecting and improving health” and
that “supports research in the causes, diagnosis, prevention, and cure of human diseases.”
The proposed research is relevant to the NIGMS 2015-2020 strategic plan: “Objective 1-1:
Invest in and sustain a broad and diverse portfolio of highly meritorious research.”, “Objective
1-2: Promote the ability of investigators to pursue new research directions, novel scientific
insights and innovative ideas”, and “Objective 3-1: Support access to essential research
resources and the development of new technologies that enable novel scientific advances.”

## Key facts

- **NIH application ID:** 10449281
- **Project number:** 5R35GM133416-04
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Yu Gao
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $394,089
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10449281

## Citation

> US National Institutes of Health, RePORTER application 10449281, Highly sensitive proteomics method to probe cell heterogeneity at single cell resolution (5R35GM133416-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10449281. Licensed CC0.

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