# Molecular Analysis of Kinetochore Function

> **NIH NIH R35** · WHITEHEAD INSTITUTE FOR BIOMEDICAL RES · 2024 · $793,650

## Abstract

Project Summary/Abstract
The goal of my laboratory is to define the molecular mechanisms by which accurate cell division occurs. Our
efforts focus on the core cell division machinery, including the macromolecular kinetochore and the
microtubule-based mitotic spindle. Despite the central importance of the spindle and the kinetochore, the
molecular basis for their many activities remains incompletely understood. We seek to generate a coherent
molecular model for how the multiple kinetochore components and spindle-associated proteins act individually
and in an integrated manner to direct faithful chromosome segregation. For chromosome segregation to occur,
kinetochores must stably associate with a single site on each chromosome, build a large macromolecular
assembly, form robust interactions with the dynamic microtubule polymers from a bipolar mitotic spindle, and
these activities must be precisely regulated to ensure that chromosome segregation occurs with high fidelity. In
addition to the function of these molecular players in actively dividing cells, the cell division machinery must
also be differentially modulated across diverse physiological conditions, for example during meiotic cell
divisions or during the persistent cell cycle arrest that occurs in quiescent cells. To analyze these key
questions, our work uses a combination of functional genetics approaches in human cells, cell biological
studies on protein localization and dynamics, affinity purification and proteomics approaches to identify protein
interactions and modifications, and biochemical reconstitutions. For our recent work, we have also
implemented large-scale approaches to analyzing cellular phenotypes using Cas9-based optical screening,
which has transformed our ability to systematically define the contributions of human genes to cell division and
other core cellular processes
Over the next 5 years, our lab will investigate the fundamental mechanisms of cell division in human cells,
focusing on three interrelated goals: 1) Analyze the molecular basis for chromosome segregation, 2) Define the
basis for the cellular changes that occur during non-dividing cell states, such as quiescence and senescence,
and 3) Conduct large-scale cell biological and functional genetics approaches to analyze cell division.

## Key facts

- **NIH application ID:** 10833594
- **Project number:** 5R35GM126930-07
- **Recipient organization:** WHITEHEAD INSTITUTE FOR BIOMEDICAL RES
- **Principal Investigator:** Iain McPherson Cheeseman
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $793,650
- **Award type:** 5
- **Project period:** 2018-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833594

## Citation

> US National Institutes of Health, RePORTER application 10833594, Molecular Analysis of Kinetochore Function (5R35GM126930-07). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10833594. Licensed CC0.

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