Jon Audhya

Assistant Professor Office: 5214A Biochemical Sciences Building 440 Henry Mall Madison WI 53706 Postal address click here Phone: (608) 262-3761 audhya@wisc.edu

Education

• B.S. 1997, Brown University, Providence, RI;
• Ph.D. 2002, University of California, San Diego (S. Emr);
• Postdoctoral 2003-07, Ludwig Institute for Cancer Research (K. Oegema).

Honors & Awards

• March of Dimes Basil O'Connor Starter Scholar Award, 2010.
• American Heart Association SDG Award, 2010.
• Shaw Scientist Award, 2010.
• Helen Hay Whitney Foundation Fellowship, 2004-2007.
• DeLill Nasser Award for Professional Development in Genetics, 2006.

Research Interests

All eukaryotic cells contain an elaborate membrane system necessary for the transport and compartmentalization of various proteins and lipids. This architecture permits numerous biochemical and signaling processes to occur simultaneously within specialized organelles. While the core machinery necessary to direct vesicle movement has been largely defined, the regulatory mechanisms that modulate membrane trafficking remain poorly understood. In particular, we are interested in determining how the fates of membrane-associated proteins are regulated by developmental cues. Failure to respond efficiently to such signals can result in a variety of disease states including cancer, neurodegeneration, and diabetes. By combining high-resolution fluorescence microscopy, functional genomics approaches, and in vitro biochemistry, we have been using the nematode Caenorhabditis elegans (C. elegans) to identify critical components necessary for membrane reorganization during development.

C. elegans is a well-established model genetic system that has been in use for more than 40 years. In addition, we have found that the oocyte and early embryo of this metazoan provide an ideal setting for the study of membrane dynamics during early development. Specifically, fertilization triggers a dramatic reorganization of the membrane system that can be visualized in utero. This transition is highlighted by 1) a stereotypical developmental switch that can be exploited as a model for studying changes in membrane trafficking during cell differentiation and 2) a highly reproducible resumption of the cell cycle, permitting an examination of organelle restructuring during both meiosis and mitosis. Importantly, RNA interference (RNAi)-mediated protein depletion in C. elegans is efficient and largely independent of intrinsic protein turnover. Several genome-wide RNAi-based screens have identified the set of ~2100 genes required for embryonic viability, including ~600 genes required for embryo production (i.e. inhibition of these genes results in sterility). After carefully examining this collection, we found it to be dramatically enriched with membrane trafficking proteins. Through the characterization of this network, we hope to assemble a comprehensive map of the transport machineries necessary for early development in C. elegans, which are likely to be conserved in higher eukaryotes. Moreover, we will identify how different membrane systems interact to allow for plasticity in transport and membrane reorganization during cell proliferation and differentiation.

Publications of Note

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• Shi, A., Chen, C.C., Banerjee, R., Glodowski, D., Audhya, A., Rongo, C., and Grant, B.D. (2010). EHBP-1 functions with RAB-10 during endocytic recycling in C. elegans. Mol. Biol. Cell. In press.

• Ziel, J.W., Hagedorn, E.J., Audhya, A., and Sherwood, D.R. (2009). UNC-6 (Netrin) orients the invasive membrane of the anchor cell in C. elegans. Nat. Cell Biol. 11: 183-189.

• Audhya, A., and Desai, A. (2008). Proteomics in Caenorhabditis elegans. Brief. Funct. Genomic. Proteomic. 7: 205-210.

• Audhya, A., McLeod, I.X., Yates, J.R. III, and Oegema, K. (2007). MVB-12, a Fourth Subunit of Metazoan ESCRT-I, Functions in Receptor Downregulation. PLoS ONE. 2: e956.


• Audhya, A., Desai, A., and Oegema, K. (2007). A role for Rab5 in ER structure and nuclear envelope disassembly. J. Cell Biol. 178: 43-56.


• Portier, N., Audhya, A., Maddox, P.S., Green, R.A., Dammermann, A., Desai, A., and Oegema, K. (2007). A microtubule-independent role for centrosomes and Aurora A in nuclear envelope breakdown. Dev. Cell. 12: 515-529.


• McNally, K., Audhya, A., Oegema, K., and McNally, F.J. (2006). Katanin controls mitotic and meiotic spindle length. J. Cell Biol. 175: 881-891.


• Sato, K., Sato M., Audhya, A., Oegema, K., Schweinsberg, P., and Grant, B.D. (2006). Dynamic regulation of Caveolin-1 trafficking in the germ line and embryo of Caenorhabditis elegans. Mol. Biol. Cell. 17: 3085-3094.


• Grant, B.D., and Audhya, A. (2005). The ins and outs of endocytic transport. Nat. Cell Biol. 7: 1051-1054.


• Audhya, A., Hyndman, F., McLeod, I.X., Maddox, A.S., Yates, J.R. III, Desai, A., and Oegema, K. (2005). A complex containing the Sm protein CAR-1 and the RNA helicase CGH-1 is required for embryonic cytokinesis in Caenorhabditis elegans. J. Cell Biol. 171: 267-279.


• Sciorra, V.A., Audhya, A., Parsons, A.B., Segev, N., Boone, C., and Emr, S.D. (2005). Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a Golgi-specific Ypt31/rab-GTPase signaling pathway. Mol. Biol. Cell. 16: 776-793.


• Audhya, A., Loewith, R., Parsons, A.B., Gao, L., Tabuchi, M., Zhao, H., Boone, C., Hall, M.N., and Emr, S.D. (2004). Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J. 23: 3747-3757.


• Yu, J.W., Mendrola, J.M., Audhya, A., Keleti, D., Dewald, D., Emr, S.D., and Lemmon, M.A. (2004). Genome-wide analysis of PH domain function in Saccharomyces cerevisiae. Mol. Cell. 13: 677-688.


• Katzmann, D.J., Sarkar, S., Chu, T., Audhya, A., and Emr, S.D. (2004). Multivesicular Body Sorting: Ubiquitin ligase Rsp5 is required for the modification and sorting of Carboxypeptidase S. Mol. Biol. Cell. 15: 468-480.


• Audhya, A., and Emr, S.D. (2003). Regulation of PI4,5P2 synthesis by nuclear-cytoplasmic shuttling of the Mss4 lipid kinase. EMBO J. 22: 4223-4236.


• Odorizzi, G., Katzmann, D.J., Babst, M., Audhya, A., and Emr, S.D. (2003). Bro1 is an endosome-associated class E Vps protein that functions in the MVB-sorting pathway in Saccharomyces cerevisiae. J. Cell Sci. 115: 1893-1903.


• Audhya, A., and Emr, S.D. (2002). Stt4 PI 4-kinase localizes to the plasma membrane and functions in the Pkc1-mediated MAP kinase cascade. Dev. Cell 2: 593-605.

University of Wisconsin - Department of Biomolecular Chemistry
Last updated: 15 July 2010 Email Biomolecular Chemistry
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