A screen for damage response genes using recombination

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant) The candidate's research career began by gaining an understanding of the fundamentals of recombination, in particular the genetics of homologous recombination (HR). Initially, as a graduate student, the candidate used the well-understood genetic system Saccharomyces cerevisiae. The candidate then moved on to work with a mouse model system during postdoctoral studies, being successful in establishing a novel assay system that allowed the determination that both the endogenous level of HR and the carcinogen induced HR were dependent upon the damage response pathway. Information and experience gained from these studies directed the candidate to the hypothesis that there are other cellular components that affect genomic stability and will also play a part in cellular damage response. These ideas can be pursued using state-of-the-art RNA interference (RNAi) technology, an available Drosophila genome library of RNAi and Drosophila tissue culture. This study will provide the resources, tools and data required to eventually establish an independent research group and launch an independent academic career. As a longer-term goal, the candidate hopes to establish a novel in vivo recombination assay and utilize it to examine both the genes identified in this proposal and other well established determinants (genetic and pharmacological) of genomic stability in an in vivo and tissue specific manner. Information gained from these studies, together with the novel tools established, should open up a wealth of research opportunities. This project has been made possible by the candidate's present position and mentor Dr. Philip Leder, who has encouraged the development of independent ideas and has taken a strong interest in this project. In addition to the highly supportive research group, the department provides an interactive community that fosters many collaborative opportunities. The objective of this project is to determine as yet unidentified components of the cellular damage response system that are responsible for either maintaining a basal frequency of HR in the presence of endogenous damage or the induction of HR following exposure to an exogenous agent. The specific aims are to: 1) develop and conduct a genetic screen for modifiers of HR in Drosophila using an available RNAi library and 2) determine whether mammalian homologues of two or three identified Drosophila genes act in an analogous fashion. From this work I hope to identify the genes that will form the basis of my future work.
StatusFinished
Effective start/end date9/1/045/31/10

Funding

  • National Institutes of Health: $108,000.00
  • National Institutes of Health: $105,462.00
  • National Institutes of Health: $108,000.00

ASJC

  • Environmental Science(all)
  • Medicine(all)

Fingerprint Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.