# Development of New Proteomics Technology and its Application to Study Cellular Organization

> **NIH NIH R35** · PRINCETON UNIVERSITY · 2022 · $395,073

## Abstract

Development of New Proteomics Technology and its Application to Study Cellular
Organization
The broad goal of our lab is to obtain a systems level understanding of cellular organization and
develop proteomics technology that facilitates this research. Thanks to the human genome
project, we have a near complete parts list of all molecules making up cells, but we still very
poorly understand how all these molecules come together and organize marvelously into a living
system. So far this organization has been mostly studied by looking carefully at one protein at a
time. While this approach has been tremendously successful, it cannot address the higher
levels of complexity in biological systems that arises from the interplay of a myriad of
components. Looking at one molecule at a time seems to be serious hindrance towards
understanding biology. Rather, we have to start investigating the entire system all at once.
Recent progress in multiplexed proteomics enables us to observe thousands of proteins
simultaneously among multiple conditions. In combination with classical biochemical
approaches this allows us to reveal collective behavior and emergent properties we would have
no chance to discover otherwise. My lab is broadly interested in systems-level cellular
organization. Towards this goal, this proposal contains two parts. The first part describes how
we aim to decipher how the proteome partitions between nucleus and cytoplasm in early
development and decode how the embryos uses differential nuclear composition for the
appropriate timing of transcription and nuclear size control. The second part of this proposal
outlines how we intend to improve quantitative proteomics technology. Proteomics has become
very powerful. Nevertheless, severe shortcomings in respect to sensitivity, data quality and
accessibility remain. We strive to address these problems. Over the last year, we have
developed a new method for quantitative shotgun proteomics (TMTc+), which produces data
with unmatched sensitivity and measurement quality while reducing cost. Next, we aim to
combine TMTc+ with a targeted approach. We anticipate that this will enable us to quantify
proteins down to the lowest abundant transcription factors. This new technology will benefit our
own research of cellular organization, but more generally will benefit researchers that are
interested in differential protein expression levels to study basic biology or disease.

## Key facts

- **NIH application ID:** 10436241
- **Project number:** 5R35GM128813-05
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Martin Wühr
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $395,073
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10436241

## Citation

> US National Institutes of Health, RePORTER application 10436241, Development of New Proteomics Technology and its Application to Study Cellular Organization (5R35GM128813-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10436241. Licensed CC0.

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