The goal of this project is to comprehensively understand the molecular mechanisms leading to the positioning of the mitotic spindle in the budding yeast Saccaromyces cerevisiae. This process underlies asymmetric cell division and development in many cell types. Spindle positioning involves the interaction of astral microtubules (MTs) with polarized sites on the cell cortex. In many cases, this process also requires the actin cytoskeleton. The capture of MT at the cell cortex shares similarities with the capture of MTs at the kinetochore and some proteins are clearly involved in both processes. Thus, understanding mechanisms for spindle positioning may also impact upon the maintenance of genome stability. Our studies therefore address mechanisms that impact on human health through implications for development and cancer. Our approach utilizes genetic, biochemical, and imaging experiments. It also benefits from our recently solved structure of one component of the system, the Bnil FH2 domain. Building on our previous work to characterize proteins associated with the plus ends of MTs and proteins involved and aspects of actin assembly that are required for spindle orientation we propose experiments with the following aims:
Aim1 : How is the force generated to orient preanaphase spindles? Aim 2: How is dynein targeted to its site of action and how is dynein activity regulated? Aim 3: How is formin-dependent actin assembly regulated in vivo?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM061345-08
Application #
7273553
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Deatherage, James F
Project Start
2000-07-01
Project End
2008-07-31
Budget Start
2007-08-01
Budget End
2008-07-31
Support Year
8
Fiscal Year
2007
Total Cost
$315,527
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
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Buttery, Shawnna M; Kono, Keiko; Stokasimov, Ema et al. (2012) Regulation of the formin Bnr1 by septins anda MARK/Par1-family septin-associated kinase. Mol Biol Cell 23:4041-53
Su, Xiaolei; Qiu, Weihong; Gupta Jr, Mohan L et al. (2011) Mechanisms underlying the dual-mode regulation of microtubule dynamics by Kip3/kinesin-8. Mol Cell 43:751-63

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