During cellular differentiation, daughter cells can have different fates. These fates may reflect the development of an organism, or they can be a manifestation of a pathology such as tumorigenesis. While significant progress has been made in understanding the regulatory mechanisms responsible for generating these different fates, how the asymmetry is initiated remains a central issue. I propose to investigate this question in a simple model system, the Gram-positive bacterium Bacillus subtilis that undergoes a form of asymmetric division. Several regulatory molecules involved in this process become localized to a site in the dividing bacteria separating the two cellular compartments destined to become the daughter cells. These patterns of localization suggest that asymmetry may derive from the particular orientation of the regulatory proteins at this site with respect to the two daughter cells. I propose a novel methodology to determine this orientation employing fusions of reporter proteins with a localized regulatory protein and assays of reporter activity using fluorescent microscopy. Knowledge of the spatial orientation of regulatory proteins may lead to-further understanding of how pathological cellular differentiation occurs.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32GM019729-03
Application #
6178857
Study Section
Special Emphasis Panel (ZRG5-MBC-2 (01))
Program Officer
Tompkins, Laurie
Project Start
1998-07-01
Project End
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
3
Fiscal Year
2000
Total Cost
$39,232
Indirect Cost
Name
Harvard University
Department
Microbiology/Immun/Virology
Type
Schools of Arts and Sciences
DUNS #
071723621
City
Cambridge
State
MA
Country
United States
Zip Code
02138
Dworkin, Jonathan; Losick, Richard (2002) Does RNA polymerase help drive chromosome segregation in bacteria? Proc Natl Acad Sci U S A 99:14089-94
Dworkin, J; Losick, R (2001) Linking nutritional status to gene activation and development. Genes Dev 15:1051-4
Dworkin, J; Losick, R (2001) Differential gene expression governed by chromosomal spatial asymmetry. Cell 107:339-46
Losick, R; Dworkin, J (1999) Linking asymmetric division to cell fate: teaching an old microbe new tricks. Genes Dev 13:377-81