# Proteomics approaches for illuminating the functions of the dark kinases Nek6, Nek7 & Nek9

> **NIH NIH R03** · DARTMOUTH COLLEGE · 2021 · $164,000

## Abstract

ABSTRACT
 Mitosis is a dynamic and tightly regulated cell cycle phase that spans chromosome condensation, spindle
formation, sister chromatid separation and segregation, and cytokinesis; the failure of cells to successfully
navigate these diverse biological functions underlies many human diseases including birth defects and cancer.
The orchestration of these functions is accomplished by a complex array of protein kinase signaling, including
the understudied NIMA-related kinases Nek6, Nek7 and Nek9. Although gene depletion studies have implicated
these Nek kinases in cell division and cytokinesis, the biochemical mechanisms by which they function remain
unresolved. Thus, new research that uncovers the regulation and downstream effectors of Nek6, Nek7 and Nek9
functions has the potential to both improve our basic understanding of cell division biology as well as identify
new entry points for therapeutic intervention in human disease.
 Here, we propose to develop and deploy targeted protein degradation coupled with mass spectrometry-
based proteomics to discover new substrates and signaling networks that are regulated by Nek6, Nek7 and Nek9
kinase activities. Using a combination of CRISPR/Cas9-based targeting strategies, homology-directed repair
and genetic engineering, we will knock-in a short degron tag at endogenous loci for these kinases in cell lines of
diverse genetic and tissue origin. We will then employ quantitative proteomics methods to identify protein
phosphorylation loci that exhibit differential occupancy upon rapid depletion of the respective Nek kinase. We
expect these experiments will shed new light on the mechanisms that define cell division and will additionally
serve as a roadmap for illuminating the rest of the understudied kinome.

## Key facts

- **NIH application ID:** 10216469
- **Project number:** 1R03TR003644-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** Scott A. Gerber
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $164,000
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10216469

## Citation

> US National Institutes of Health, RePORTER application 10216469, Proteomics approaches for illuminating the functions of the dark kinases Nek6, Nek7 & Nek9 (1R03TR003644-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10216469. Licensed CC0.

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