Mechanisms of microtubule motors and chromosome segregation

NIH Pandemic-Era Grants

Pandemic Era Grants

2024

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Principal Investigator: JASON K STUMPFF
Organization: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
Fiscal Year: 2024
Award: $431,434
Funding agency: National Institute of General Medical Sciences

PROJECT SUMMARY
The accurate segregation of chromosomes by the microtubule-based mitotic spindle during mitosis is
essential for the preservation of genomic integrity. Errors in mitotic spindle function lead to chromosome
missegregation, aneuploidy, and the formation of micronuclei, all hallmarks of tumor cells. Molecular motors
of the kinesin superfamily play important mechanical roles in controlling the movement and organization of
chromosomes within the spindle, including the generation of forces on chromosome arms, regulation of
spindle microtubule length changes, and the crosslinking and sliding of microtubule overlaps. Many of the
molecular mechanisms underlying kinesin function in cells remain poorly understood. This proposal seeks
to fill knowledge gaps in our understanding of how kinesins function at the molecular level to ensure the
accuracy of mitotic chromosome segregation. How do the structures of kinesins tune their activities for
particular roles in cells? How are these activities spatially and temporally regulated? What is the molecular
basis for cell type specific requirements of kinesin function? What are the short and long-term
consequences of abnormal kinesin activities? An interdisciplinary approach combining biophysics,
quantitative live cell imaging, and structural mutagenesis will be employed to address these outstanding
questions across biological scales from the single molecule to single cell, to tissue and whole organism
levels.

Terms: <Address><Aneuploid><Aneuploidy><Biological><Biophysics><Body Tissues><Cancers><Cell Body><Cells><Chromosomal Organization><Chromosomal Structure><Chromosome Arm><Chromosome Organization><Chromosome Segregation><Chromosome Structures><Congenital Disorders><Development><Ensure><Generations><Genetics-Mutagenesis><Genome Instability><Genomic Instability><Kinesin><Knowledge><Lead><Length><M Phase><Malignant Neoplasms><Malignant Tumor><Mechanics><Micro-tubule><Microtubules><Mitosis><Mitosis Stage><Mitotic Chromosome><Mitotic spindle><Molecular><Molecular Motors><Motor><Movement><Mutagenesis><Mutagenesis Molecular Biology><Pb element><Play><Proteins><Public Health><Regulation><Research><Role><Slide><Structure><Syndrome><Tissues><Trisomy><Tumor Cell><Whole Organism><biologic><biophysical foundation><biophysical principles><biophysical sciences><body movement><cancer progression><cell type><chromosomal missegregation><chromosome division><chromosome missegregation><crosslink><developmental><genome integrity><genomic integrity><heavy metal Pb><heavy metal lead><interdisciplinary approach><live cell image><live cell imaging><live cellular image><live cellular imaging><malignancy><mechanic><mechanical><micronucleus><multidisciplinary approach><neoplasm progression><neoplasm/cancer><neoplastic cell><neoplastic progression><preservation><prevent><preventing><protein function><single molecule><social role><tumor progression>