University of Connecticut

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CCAM Seminar Series - Khodjakov

Thursday, March 2, 2017
12:00pm – 1:00pm

UConn Health
CGSB, CCAm Conference Room, r1673, 400 Farmington Ave

CCAM Seminar Series Speaker: Alexey Khodjakov Ph.D.,Research Scientist VI – Wadsworth Center Adjunct Professor - RPI Cellular & Molecular Basis of Diseases Title: “Mitotic spindle assembly: basic principles and facilitating mechanisms” Abstract: Segregation of chromosomes during cell division is enacted by a self-assembling molecular machine termed the mitotic ‘spindle’. The basic principle of spindle self-assembly was formulated in the “search-and-capture” (S&C) hypothesis: dynamic centrosomal microtubules explore space until they are captured and stabilized by the ‘kinetochores’ residing at the chromosome’s centromere. However, unguided stochastic S&C is quite inefficient and it fails to explain the rapid (<10 min) and low-error spindle assembly observed in human cells. A series of mechanisms that facilitate S&C have been identified in the recent years. These mechanisms include formation of diffusible gradents that guide centrosomal microtubules towards the chromosomes, nucleation of non-centrosomal microtubules in the immediate vicinity of kinetochores, a combination of the outward- and inward-directed forces that are produced by the molecular motors on the chromosome arms and at the kinetochores respectively. Relative contributions made by each of these mechanisms during normal spindle assembly remain unknown. By combining live-cell recordings of chromosome behavior and correlative electron microscopy we investigate how many of the 46 chromosomes in human cells become incorporated in the spindle via a direct capture of centrosomal microtubules and how many chromosomes rely on the alternative, non centrosomal mechanisms. Surprisingly, our data suggest that within the first 2-3 minutes after the disassembly of nuclear envelope in non-transformed human cells, most kinetochores become attached to the ends of short non-centrosomal microtubules. These initial attachments potentially help to orient and distribute chromosomes into a spatial pattern that actively present kinetochores to the searching centrosomal microtubules during later stages of spindle assembly. We are currently testing involvement of various motor proteins into the initial interaction between the kinetochores and non-centrosomal microtubules.

Contact:

Tiffany x6103

Center for Cell Analysis and Modeling (primary), School of Medicine

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