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Krogan, Nevan
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| Location: | 1700 4th Street 408E | | Phone Number: | 415-476-2980 | | FAX Number: | 415-514-2073 | | Email: | krogan@cmp.ucsf.edu | | Lab Groups: | Faculty Krogan |
| Research Statement | | My lab focuses on generating large-scale, quantitative genetic and physical interaction maps in several organisms. We employ an affinity purification/mass spectrometry strategy for identification of protein-protein interactions and, using this approach, have defined a high-quality protein-protein interaction dataset for budding yeast (Krogan et al., Nature, 2006; Collins et al., MCP, 2007). We are employing a similar strategy to create protein-protein interaction maps for other organisms including S. pombe, M. tuberculosis (Jeff Cox) as well as an HIV-host physical map (Alan Frankel)
However, even knowledge of the stoichiometry, affinity, and lifetime of every protein-protein interaction would not reveal the functional relationships between and within such complexes. Genetic interactions can provide functional information that is largely invisible to protein-protein interaction datasets. In collaboration with Jonathan Weissman, we have developed an approach, termed E-MAP (epistatic miniarray profile), which can provide information on genetic interactions. E-MAPs comprise comprehensive and quantitative measurements of genetic interactions between pairs of mutations from sets of genes that are functionally related. Since this analysis is quantitative, both negative (e.g. SSL) and positive (e.g. suppression) interactions can be identified. Positive interactions often identify proteins that are complexed or functioning in the same functional pathway. We have used the E-MAP approach to genetically interrogate sets of genes in S. cerevisiae involved in various processes including the early secretory pathway (Schuldiner et al., Cell, 2005) and chromosome function (Collins et al., Nature, 2007). We are presently generating E-MAPs that focus on other biological processes and developing E-MAP technology for other organisms, including S. pombe (Roguev et al., Nature Methods, 2007).
Ultimately, we combine the genetic and protein-protein interaction datasets and extract specific and testable hypotheses from these maps. We are also developing tools and software to help facilitate integration and navigation of this different information with the ultimate goal of further understanding cell physiology. |
Publications | | Keogh, M. C., J. Kim, M. Downey, J. Fillingham, D. Chowdbury, J. C. Harrison, M. Onishi, N. Datta, S. Galicia, A. Emili, J. Lieberman, X. Shen, S. Buratowski, J. E. Haber, D. Durocher, J. F. Greenblatt and N. J. Krogan. 2006. A phosphatase complex required for dephosphorylation of gH2A.X and DNA damage checkpoint recovery in S. cerevisiae. Nature 439:497-501.
Keogh, M. C., S. K. Kurdistani, S. A. Morris, S. H. Ahn, V. Podolny. S. R. Collins, M. Schuldiner, K. Chin, T. Punna, N. J. Thompson, C. Boone, A. Emili, J. S. Weissman, T. R. Hughes, B. D. Strahl, M. Grunstein, J. F. Greenblatt, S. Buratowski and N. J. Krogan. 2005. Cotranscriptional Set2 methylation of histone H3 lysine 36 recruits a repressive Rpd3 complex. Cell 123:593-605. |
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