The study of stem cells is scientifically interesting and has the potential to revolutionize approaches to the treatment of diseases. To fully realize this potential, stem cell biology must first be understood at a deeper level, and that is what this proposal sets out to accomplish.

Dr. Laski's lab has taken a genetic approach to stem cell research using the fruit fly Drosophila melanogaster. A mutant with a female-sterile phenotype that has tumorous ovaries has been isolated. In wild type, oogenesis initiates when a germline stem cell divides and gives rise to two daughter cells, one remains a stem cell, while the other becomes a cystoblast. This cystoblast then divides incompletely four times creating a 16 cell cyst interconnected by ring canals. One of these 16 cells develops into the oocyte and later into the egg, the remaining 15 become nurse cells. An ovary is said to be tumorous when these cystoblasts do not differentiate into 16-cell cysts, creating an ovary with an over-abundance of stem cells and cystoblasts, and a lack of 16-cell cysts and developing egg chambers.

The tumorous ovary mutant isolated in Dr. Laski's lab has mutations in two different genes, and the combination of these mutations gives rise to the tumorous phenotype. These genes are RNA binding protein 9 (Rbp9) and vasa. In addition to causing the tumorous ovary, it was determined that vasa and Rbp9 are required for proliferation of the germline stem cells, and in combination with the gene mei-P26, also function in maintenance of the germline stem cells. These results are exciting, especially because it sheds new insight into the function of vasa. vasa is conserved throughout the metazoa and in every animal studied, including humans, vasa expression is exclusive to the germline. Therefore finding new developmental functions for vasa in the fruit fly will have implications for human biology.

To understand the biology of stem cells, it is necessary to understand the complex interactions between dozens of genes. The proposed experiments will continue the analysis of mei-P26, Rbp9 and vas. This analysis will build upon the framework of genes known to be involved in regulatory pathways of stem cell growth and differentiation, a framework that must be deciphered before a complete understanding of germline stem cell biology is accomplished.

In addition to the scientific impact, a broader societal impact will also be achieved by the work proposed in this grant, primarily in the area of scientific education of minority students, women and undergraduates. The proposed work will primarily be done by a female postoctoral fellow and a minority graduate student. Dr. Laski's lab also participates in the UCLA CARE Program, which recruits minority students from local junior colleges and places them in a lab where they receive research experience. One of the Dr. Laski's previous CARE students, Gwen Cabrera, recently published a first author manuscript in the journal Genesis. This year's CARE student plans to transfer to UCLA next year, at which time she will work in the Laski lab on a year-round basis helping to determine how stem cells function.

Agency
National Science Foundation (NSF)
Institute
Division of Integrative Organismal Systems (IOS)
Application #
0236209
Program Officer
Judith Plesset
Project Start
Project End
Budget Start
2003-08-01
Budget End
2006-07-31
Support Year
Fiscal Year
2002
Total Cost
$360,000
Indirect Cost
Name
University of California Los Angeles
Department
Type
DUNS #
City
Los Angeles
State
CA
Country
United States
Zip Code
90095