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BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Mudgett, Mary Beth Associate Professor of Biology Stanford University eRA COMMONS USER NAME (credential, e.g., agency login) MUDGETTMARY_BETH EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Ithaca College, Ithaca, NY University of California, Los Angeles, CA University of California, Los Angeles, CA University of California, Berkeley, CA B.A. Ph.D. Postdoc Postdoc 05/89 06/94 12/95 12/01 Biochemistry Biochemistry Biochemistry Plant-Microbe Inter. A. Personal Statement My laboratory studies the biochemical mechanisms used by bacterial pathogens to alter plant physiology during infection. The long-term goal of our work is thus to elucidate the biochemical activities of bacterial virulence factors secreted by the type III secretory (T3S) apparatus, identify their host targets, and provide fundamental knowledge of how perturbation of these distinct nodes in plant signal transduction pathways leads to bacterial pathogenesis. To do so, we study bacterial leaf spot disease in tomato caused by the Gram-negative, facultative parasite Xanthomonas campestris pathovar vesicatoria (Xcv). We performed a novel genetic screen to identify new Xcv T3S effector proteins translocated directly into host plant cells during infection. We biochemically characterized the function of three Xcv T3S effectors – XopN, XopD, and AvrBsT. We have discovered that these effectors target three distinct nodes in defense signal transduction. We have shown that: 1) XopN encodes a novel scaffolding-like protein that suppresses PAMP-triggered immunity and physically interacts with a tomato receptor kinase and the 14-3-3 protein TFT1. 2) XopD encodes a plant-specific SUMO protease that alters host transcription, promotes pathogen growth, and suppresses host defense responses at the late stages of tissue colonization. 3) AvrBsT interferes with lipid signaling, resulting in the activation of effector-triggered immunity. Ongoing work is aimed at elucidating how the identified host targets regulate plant immunity during pathogen attack, as well as the biochemical characterization of novel Xcv effector activities. Understanding how plant immunity is regulated and how bacterial pathogens manipulate their hosts is fundamental knowledge required for the prevention and elimination of plant disease. B. Positions and Honors Positions 2002-2009 2010- Assistant Professor of Biology, Stanford University, Stanford, CA Associate Professor of Biology, Stanford University, Stanford, CA Other Experience and Professional Memberships 1996 – Member of International Society of Plant-Microbe Interactions 1996 – American Society for Plant Biology 2005 – NIH HIBP Study Section, Ad hoc 2008 – NSF IOS Symbiosis, Defense and Self-recognition, Ad hoc and Grant Review Panel 2009 – 2011 Senior Editor, Molecular Plant Pathology 2009 – Research Advisory Board, Pierce’s Disease/Glassy Wing Sharp Shooter Program 2010 – College Board AP Biology Curriculum Review and Research 2010 – Editor, Frontiers in Plant-Microbe Interactions 2012 Co-organizer, BARD Workshop: Microbial Virulence Determinants & Plant Immunity, Israel 2012 – Chair, Pierce’s Disease/Glassy Wing Sharp Shooter Research Advisory Board 2012 – Board Member, International Society for Molecular Plant-Microbe Interactions Honors 1990 1992 1997-1999 2004-2010 2005-2006 2008 2011-2014 2013-2014 Graduate Teaching Assistant Award, UCLA Graduate Research Achievement Award, UCLA National Research Service Award, NIH Terman Fellow, Stanford University Hellman Faculty Scholar, Stanford University Teacher of the Year, Associated Students of Stanford University Chamber Fellowship, Stanford University VPUE Faculty Scholar, Stanford University C. Selected Peer-reviewed Publications (selected from 30 peer-reviewed publications). Most relevant to the current application 1. Cunnac, S., Wilson, A., Nuwer, J., Kirik, A., Baranage, G., and Mudgett, M. B. (2007) The conserved Arabidopsis carboxylesterase SUPPRESSOR OF AVRBST-ELICITED RESISTANCE inhibits defenses triggered by the AvrBsT Type III Effector. Plant Cell 19, 688-705. PMID:17293566. 2. Kim, J.-G., Taylor, K. W., Hotson, A., Keegan, M., Schmeltz, E. A., and Mudgett, M. B. (2008) XopD SUMO protease affects host transcription, promotes pathogen growth, and delays symptom development in Xanthomonas-infected tomato leaves. Plant Cell 20, 1915-1929. PMID:18664616. 3. Kirik, A. and Mudgett, M. B. (2009) SOBER1 hydrolase suppresses phosphatidic acid accumulation and plant defense in response to bacterial T3S effector AvrBsT. Proc. Natl. Acad. Scie. U.S.A. 106, 2053220537. PMID:19918071. 4. Taylor, K. W., Kim, J.-G., Su, X. B., Aakre, C. D., Roden, J. A., Adams, C. M., and Mudgett, M.B. (2012) Tomato TFT1 is required for PAMP-triggered immunity and mutations that prevent T3S effector XopN from binding to TFT1 attenuate Xanthomonas virulence. PLoS Pathogens 8, e1002768. PMID:22719257. 5. Kim, J.-G. Stork, W., and Mudgett, M. B. (2013) Xanthomonas type III effector XopD desumoylates tomato transcription factor SlERF4 to suppress ethylene responses and promote pathogen growth. Cell Host Microbe 13, 1-12. PMID:23414755. Additional recent publications of importance to the field (in chronological order) 1. Orth, K., Xu, Z., Mudgett, M. B., Bao, Z. Q., Palmer, L. E., Bliska, J. B., Mangel, W. F., Staskawicz, B., and Dixon, J. E. (2000) Disruption of signaling byYersinia effector YopJ, a ubiquitin-like protein protease. Science 290, 1594-1597. PMID:11090361. 2. Hotson, A., Chosed, R., Shu, H., Orth, K., and Mudgett, M. B. (2003) Xanthomonas type III effector XopD targets SUMO-conjugated proteins in planta. Mol. Microbiol. 50, 377-389. PMID:14617166. 3. Roden, J. A., Belt, B., Ross, J.B., Tachibana, T., Vargas, J., and Mudgett, M. B. (2004) A genetic screen to isolate type III effectors translocated into pepper cells during Xanthomonas infection. Proc. Natl. Acad. Sci. U.S.A. 101, 16624-16629. PMID:15545602. 4. Mudgett, M. B. (2005) New insights to the function of phytopathogenic bacterial type III effectors in plants. Ann. Rev. Plant Biol. 56, 509-531. PMID:15862106. 5. Doyle, E. A., Lane, A. M., Sides, J. M., Mudgett, M. B., and Monroe, J. D. (2007) An alpha-amylase (At4g25000) in Arabidopsis leaves is secreted and induced by biotic and abiotic stress. Plant Cell Environ. 30, 388-398. PMID:17324226. 6. Swartz, T.E., Tseung, T.-S., Frederickson, M., Paris, G., Comerci, D. J., Rajashekara, G., Kim, J.-G., Mudgett, M.B., Splitter, G., Ugalde, R. A., Goldbaum, F. A., Briggs, W. R., and Bogomolni, R. A. (2007) Blue-light-activated Histidine kinases: two-component sensors in bacteria. Science 317, 1090-1093. PMID:17717187. 7. Kim, J.-G., Xinyan, L., Roden, J., Taylor, K., Aakre, C., Su, B., Lalonde, S., Kirik, A., Chen, Y., Baranage, G., McLane, H., Martin, G. B., and Mudgett, M. B. (2009) Xanthomonas T3S effector XopN suppresses PAMP-triggered immunity and physically interacts with a tomato atypical receptor-like kinase and TFT1 in planta. Plant Cell 21, 1305-1323. PMID:19366901. 8. Chen, L-Q., Hou, B.-H., Lalonde, S., Takanaga, H., Hartung, M.L., Qu, X.-Q., Guo, W.-J., Kim, J.-G., Underwood, W., Chaudhuri, B., Chermak, D., Antony, G., White, F. F., Somerville, S. C., Mudgett, M. B., and Frommer, W. B. 2010) Sugar transporters for intercellular exchange and nutrition of pathogens. Nature 468, 527-532. PMID:21107422. 9. Kim, J.-G., Taylor, K., and Mudgett, M. B. (2011) Comparative analysis of the XopD T3S effector family in plant pathogenic bacteria. Mol. Plant. Pathol. 12, 715-730. PMID:21726373. 10. Sonnewald, S., Priller, J., Schuster, J. Glickmann, E., Hajirezaei, M.-R., Siebig, St., Mudgett, M. B., and Sonnewald, U. (2012) Regulation of cell wall-bound invertase in pepper leaves by Xanthomonas campestris pv. vesicatoria Type Three Effectors. PLoS One 7(12), e51763. PMID:23272161. C. Research Support Ongoing Research Support NIH/NIGMS 2 RO1 GM068886-06A1 Mudgett (PI) 09/30/04 – 04/30/14 Characterization of lipid signaling altered by T3S effector AvrBsT The goal of this project is to determine how AvrBsT-triggered lipid signals activate immune signal transduction during bacterial infection in Arabidopsis. BSF 2011069 Mudgett (co-PI) 10/01/12 – 09/30/16 Tomato 14-3-3 proteins: signaling components of plant immunity and targets of bacterial virulence determinants The goal of this project is to determine the Xanthomonas T3S effector suite that interact with tomato 14-3-3 proteins to determine how and why 14-3-3’s are being co-opted during infection to promote pathogenesis. Completed Research Support DOE DE-FG02-03ER15443 Mudgett (PI) 09/01/03 – 08/31/06 Molecular communication between Xanthomonas campestris pv. vesicatoria and its plant hosts: Genome-wide survey to identify type III effector proteins and to characterize their role in plant pathogenesis. The goal of this project was to identify type III effectors in Xanthomonas to gain insight to the virulence factors that control bacterial spot disease in tomato. DOE DE-GF-2-03ER15443-A002 Mudgett (PI) 09/01/06 – 08/31/07 Biochemical characterization of the interaction between the Xanthomonas type III effector XopN and a tomato LRR-RLK. The goal of this project was to identify plant binding partners for the bacterial protein XopN to begin to elucidate the nodes in the plant immune system that under attack during infection. BARD Mudgett (co-PI) 02/05/12 – 02/09/12 BARD Workshop: Microbial virulence determinants and plant immunity. The goal of this workshop was to unite Israeli and American scientists working on plant-microbe interactions to share research technology, establish new collaborations, and plan for future work in the field. NSF/IOS 1160811 Mudgett (PI) 01/01/12 – 06/30/12 BARD Workshop on microbial virulence determinants and plant innate immunity. Funding was obtained to support young and established American scientists to attend the workshop in Israel. Company of Biologists LTD Mudgett (PI) 01/31/12 Workshop support for European scientists Funding was obtained to support participants from Europe and Asia to attend the workshop in Israel. NSF/IOS 821801 Mudgett (PI) 09/01/08 – 08/31/13 Characterization of XopN, a heat-repeat TTSS effector required for Xanthomonas pathogenesis in tomato. The goal of this project was to determine how the bacterial protein XopN suppresses host immune signaling by targeting the receptor kinase TARK1 and the 14-3-3 phospho-binding protein TFT1.