Faculty: Anjon Audhya, PhD
Assistant Professor of Biomolecular Chemistry
Director of Molecular and Cellular Pharmacology (4/2014)
|Contact:||5214a Biochemical Sciences|
440 Henry Mall
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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 of ‘sterile’ genes, 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.
Honors & Awards
- March of Dimes Basil O'Connor Starter Scholar Award, 2010.
- American Heart Association SDG Award, 2010.
- Shaw Scientist Award (2010)
- DeLill Nasser Award for Professional Development in Genetics (2006)
Selected Publications: (Find publications on PubMed)
- Mayers JR, Wang L, Pramanik J, Johnson A, Sarkeshik A, Wang Y, Saengsawang W, Yates JR 3rd, Audhya A. Regulation of ubiquitin-dependent cargo sorting by multiple endocytic adaptors at the plasma membrane. Proc Natl Acad Sci U S A. 2013 Jul 16;110(29):11857-62. doi: 10.1073/pnas.1302918110. Epub 2013 Jul 1. PMID: 23818590 [PubMed - in process]
- Beetz C, Johnson A, Schuh AL, Thakur S, Varga RE, Fothergill T, Hertel N, Bomba-Warczak E, Thiele H, Nürnberg G, Altmüller J, Saxena R, Chapman ER, Dent EW, Nürnberg P,Audhya A. (2013). Inhibition of TFG function causes hereditary axon degeneration by impairing endoplasmic reticulum structure. Proc Natl Acad Sci U S A. 2013 Mar 26;110(13):5091-6. doi: 10.1073/pnas.1217197110. Epub 2013 Mar 11 PMID: 23479643 [PubMed - indexed for MEDLINE]
- Hanna M, Wang L, Audhya A. (2013). Worming our way in and out of the Caenorhabditis elegans germline and developing embryo. Traffic. 2013 May;14(5):471-8. doi: 10.1111/tra.12044. Epub 2013 Feb 6. PMID: 23331906 [PubMed - in process]
- Mayers JR and Audhya A (2012). Vesicle formation within endosomes: An ESCRT marks the spot. Commun Integr Biol. 5:50-56. PMID: 22482010
- Schuh AL and Audhya A (2012). Phosphoinositide signaling during membrane transport in Saccharomyces cerevisiae. Subcell Biochem. 59:35-63. PMID: 22374087
- Park S, Patterson EE, Cobb J, Audhya A, Gartenberg MR, Fox CA (2011). Palmitoylation controls the dynamics of budding-yeast heterochromatin via the telomere-binding protein Rif1. Proc Natl Acad Sci U S A. 108:14572-14577. PMID: 21844336
- Green R, Kao H, Audhya A, Arur S, Mayers JR, Fridolfsson H, Schulman M, Schloissnig S, Niessen S, Laband K, Wang S, Starr D, Hyman A, Schedl T, Desai A, Piano F, Gunsalus KC, and Oegema K. (2011) A high-resolution C. elegans essential gene network based on phenotypic profiling of a complex tissue. Cell. 145:470-482. (# denotes equal contribution)
- Fyfe I, Schuh AL, Edwardson JM, and Audhya A (2011). Association of the endosomal sorting complex ESCRT-II with the Vps20 subunit of ESCRT-III generates a curvature-sensitive complex capable of nucleating ESCRT-III filaments. J Biol Chem. 286:34262-34270. PMID: 21835927
- Witte K, Schuh AL, Hegermann J, Sarkeshik A, Mayers JR, Schwarze K, Yates JR 3rd, Eimer S, and Audhya A (2011). TFG-1 function in protein secretion and oncogenesis. Nat Cell Biol. 13:550-558. PMID: 21478858
- Mayers JR, Fyfe I, Schuh AL, Chapman ER, Edwardson JM, and Audhya A (2011). ESCRT-0 assembles as a heterotetrameric complex on membranes and binds multiple ubiquitinylated cargoes simultaneously. J Biol Chem. 18;286:9636-9645. PMID: 21193406
- Zaidel-Bar R, Joyce MJ, Lynch AM, Witte K, Audhya A, Hardin J (2010). The F-BAR domain of SRGP-1 facilitates cell-cell adhesion during C. elegans morphogenesis. J Cell Biol. 191:761-769. PMID: 21059849
- Rodenas E, Klerkx EP, Ayuso C, Audhya A., and Askjaer P. (2009). Early embryonic requirement for nucleoporin Nup35/NPP-19 in nuclear assembly. Dev. Biol. 327:399-409.
- Ziel JW, Hagedorn EJ, Audhya A, and Sherwood DR. (2009) UNC-6 (Netrin) orients the invasive membrane of the anchor cell in C. elegans. Nat. Cell Biol. 11:183-189.
- Baird D, Stefan CJ, Audhya A, Weys S, and Emr SD. (2008). Assembly of the PtdIns 4-kinase Stt4 complex at the plasma membrane requires Ypp1 and Efr3. J. Cell Biol. 183: 1061-1074.
- Audhya, A., and Desai, A. (2008). Proteomics in Caenorhabditis elegans. Brief. Funct. Genomic. Proteomic. 7:205-210.
- Kachur, T.M., Audhya, A., and Pilgrim D.B. (2008). UNC-45 is required for NMY-2 contractile function in early embryonic polarity establishment and germline cellularization in C. elegans. Dev. Biol. 314: 287-299.
- Green, R.A., Audhya, A., Pozniakovsky, A., Dammermann, A., Pemble, H., Monen, J., Portier, N., Hyman, A., Desai, A., and Oegema, K. (2008). Expression and imaging of fluorescent proteins in the C. elegans gonad and early embryo. Methods Cell Biol. 85: 179-218.