# Understanding Cell Division

> **NIH NIH R35** · OKLAHOMA MEDICAL RESEARCH FOUNDATION · 2024 · $460,350

## Abstract

Cell division involves complex interactive pathways that coordinate chromosome movements with cell cycle
transitions. While many regulators that modulate spindle microtubule dynamics, chromosome behavior, and cell
cycle control have been identified, complete understanding of their functions and interactions in controlling
spindle structure and chromosome movement at different stages of mitosis remains incomplete. This deficit in
understanding mitosis is due to the limited spatial and temporal resolution of current phenotypic analyses of
manipulations such as protein deletion and mutant expression. The mitotic parts list is large, but continued
discovery of novel mitotic components indicates that it is not yet complete, particularly for vertebrates.
Bioinformatic guidance with the GAMMA algorithm continues to foster our identification of new mitotic regulators
that were missed in previous screens including whole genome screens. Using innovative methods correlating in
vivo and in vitro analysis, members of the laboratory target known and newly identified mitotic regulators, to test
their roles in moving chromosomes during prometaphase, metaphase, and anaphase, in controlling spindle
microtubule dynamic turnover, in generating mechanical tension between kinetochores and microtubules, and
in directing mitotic cell cycle progression. The proposed projects combine many advanced strategies including
high resolution, low phototoxicity, light sheet microscopy, degron tagging of endogenous genes, antibody-
mediated protein degradation, and instantaneous, live cell quantitation of kinetochore-microtubule tension.
These techniques are coupled with advanced image analysis. This new sophistication of phenotype analysis will
vertically advance understanding of the functions of known and newly discovered mitotic regulators at all stages
of mitosis. Further, to elucidate important protein interactions and molecular pathways, in vitro and in vivo
contacts of known and novel mitotic regulators will be mapped through established methods (e.g.
immunoprecipitation and mass spectroscopy) and through application of new innovations such as microscale
thermophoresis and mammalian two-hybrid analysis. Specific projects include characterization of established
and newly implicated mitotic regulators, investigation of a novel mechanism of chromosome instability in induced
pluripotent stem cells, and evaluation of the causes and consequences of “cohesion fatigue,” a spontaneous,
progressive loss of source of chromosome structure in cells stalled at metaphase.

## Key facts

- **NIH application ID:** 10763765
- **Project number:** 2R35GM126980-06
- **Recipient organization:** OKLAHOMA MEDICAL RESEARCH FOUNDATION
- **Principal Investigator:** GARY J. GORBSKY
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $460,350
- **Award type:** 2
- **Project period:** 2018-07-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10763765

## Citation

> US National Institutes of Health, RePORTER application 10763765, Understanding Cell Division (2R35GM126980-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10763765. Licensed CC0.

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