Organization of the Mammalian Mitotic Spindle

NIH RePORTER · NIH · R37 · $191,351 · view on reporter.nih.gov ↗

Abstract

Accurate chromosome segregation is essential for the propagation of species and the viability of cells, and is driven by a complex microtubule-based structure called the spindle. Intensive biochemical, genetic, and proteomic efforts provide an extensive catalogue of proteins that participate in spindle organization and spindle-dependent chromosome movement. However, these efforts don’t reveal the molecular mechanisms that ensure faithful chromosome segregation in mammalian cells. Recently, we showed that the most common cause of chromosome mis-segregation in human tumor cells is the persistence of kinetochore-microtubule (K- MT) attachment errors. However, our understanding for how K-MT attachments are regulated to promote error correction remains starkly incomplete. We don’t understand how different molecular components create a coherent output to fine-tune K-MT attachment stability during cell cycle transitions. We also don’t understand how aneuploidy influences genome stability and cell survival. It is our goal in the forthcoming funding period to combine biochemical methods and live cell imaging to test models and determine the mechanisms of the regulation of K-MT attachments in mitosis. Understanding these mechanisms could lead to new therapeutic approaches for cancer treatment. The specific goal for this administrative supplement is to request funds to purchase a replacement microscope to facilitate the pursuit of our aims. Our existing microscope is fifteen years old and is used daily for fixed and live mammalian cell imaging to understand mechanisms contributing to faithful chromosome segregation. Progress toward completing our stated goals of the parent project is frequently hampered by failure of different elements (light paths, stage, reflector turret, etc) of this microscope. Thus, we seek funding to replace our aging equipment to facilitate the efficient completion of our aims in the parent project.

Key facts

NIH application ID
10134573
Project number
3R37GM051542-24S1
Recipient
DARTMOUTH COLLEGE
Principal Investigator
Duane A. Compton
Activity code
R37
Funding institute
NIH
Fiscal year
2020
Award amount
$191,351
Award type
3
Project period
1996-08-01 → 2023-02-28