# Chemical Biology of Cell Division

> **NIH NIH R35** · ROCKEFELLER UNIVERSITY · 2020 · $82,900

## Abstract

Project Summary/Abstract: Our long-term goal is to decipher the molecular mechanisms that ensure the
proper assembly and function of the microtubule-based structures needed for error-free cell division.
Essentially all the proteins required for cell division in human cells have now been identified. However,
uncovering mechanisms has remained challenging as cell division is rapid and can be completed in <1 hour in
human cells, with key steps taking only minutes. In addition, the microtubule-based structures needed for cell
division require constant energy input to maintain shape and size, cannot be readily isolated in native forms
and the protein-protein interactions critical for function can be transient and mitosis-specific. Finally, these
structures are micrometer-sized and can be ~1000-times larger than their protein components. We take
interdisciplinary approaches that can address these challenges and help dissect the dynamic self-assembly of
these essential structures. We have: (i) Discovered and characterized selective cell-permeable chemical
inhibitors of key proteins. These inhibitors can be powerful probes to examine cell division dynamics, as
proteins can be inhibited or activated (via relief from inhibition), within minutes in living cells. To track the
cellular responses to these fast perturbations we use state-of-the-art microscopy (e.g. lattice light-sheet
microscopy) and quantitative image analysis methods. (ii) Developed and applied iCLASPI, a chemical
proteomics approach to covalently ‘capture’ and profile transient and context-dependent protein-protein
interactions in living cells. (iii) Analyzed the self-assembly of basic structural and functional motifs (e.g. bipolar
microtubule arrays) with purified proteins. For these biochemical studies, we have assembled a ‘toolbox’ of
recombinant proteins including isotypically-pure human tubulin, the augmin complex and key microtubule-
associated motor and non-motor proteins. The proposed research, which benefits from our experience and
expertise, will focus on anaphase and cytokinesis. These final stages of cell division can be difficult to study
using approaches that cannot profile transient protein-protein interactions or do not provide precise temporal
control over protein function. We will take interdisciplinary approaches to address the following gaps in our
knowledge: (1) What are the roles of microtubule-severing proteins during the final stages of cell division? (2)
How do PRC1, a non-motor protein that selectively crosslinks antiparallel microtubules, and kinesin-4, a
microtubule plus-end directed motor protein, contribute to the assembly of the spindle midzone during
anaphase? (3) What are the minimum number of proteins needed for microtubule-dependent microtubule
formation, a key centrosome-independent microtubule nucleation pathway needed for cell division? Errors in
cell division have been linked to diseases and developmental defects. Improper cell division has also been
ex...

## Key facts

- **NIH application ID:** 10163370
- **Project number:** 3R35GM130234-02S1
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** TARUN M. KAPOOR
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $82,900
- **Award type:** 3
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10163370

## Citation

> US National Institutes of Health, RePORTER application 10163370, Chemical Biology of Cell Division (3R35GM130234-02S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10163370. Licensed CC0.

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