Program Director/Principal Investigator (Last, First, Middle): Meyskens, Frank L. 5P30CA062203-17 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 Sandmeyer, Suzanne B. Professor of Biological Chemistry eRA COMMONS USER NAME (credential, e.g., agency login) SUZANNESANDMEYER 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) Carleton College, Northfield, MN University of Washington, Seattle, WA Washington University, St. Louis, MO BA PhD Postdoc 05/73 05/80 12/83 Biology Biochemistry Genetics A. Personal statement My laboratory discovered the Ty3 element in Saccharomyces cerevisiae and has studied it for many years. It is one of the better characterized of the major class of long terminal repeat retrotransposons known as gypsy-Ty3 type elements which resemble retroviruses in structure and function. Although we have focused on a single retrotransposons, this has led us into many areas of investigation using the S. cerevisiae model. We discovered the interaction between retrotransposons and transcription factors that can target integration, identified numerous host factors that support retrotransposition, described capsid domain functions, identified nucleoporins involved in Ty3 nuclear entry, and most recently have identified associations between Ty3 structural proteins and RNA processing body proteins that implicate them in the transition from translation to assembly. In addition to our general use of genomics as a yeast laboratory, we have specifically used Illumina sequencing to characterize Ty3 insertions into Pol III-transcribed genes in the yeast genome. My laboratory has recently initiated a metabolomics project using yeast as a model system and funded through a NSF Engineering Center. In that project we are using Affymetrix microarrays and Illumina next generation sequencing (DNA- and RNA-seq) to characterize RNA expression profiles of yeast mutants and of oleaginous yeast. Because of the similarities of yeast metabolism to the fermentation (Warburg) pathways active in tumor cells, there is considerable, albeit informal to date, transfer of interests between this systems project and research in the Cancer Center. Bioinformatics has been performed in my laboratory by a postdoctoral fellow who trained in Bioinformatics with Eric Mjolsness, Ph.D., in the Dept. of Computer Science and in collaboration with the group of Pierre Baldi, Ph.D. also in the Dept. of Computer Science here at UCI. Among activities outside the university, I served for two years as the Chair of the Senior Editors of Genetics under Editor-in-Chief Elizabeth Jones and worked closely with a group of Senior Editors in order to revitalize the journal and the editorial process and prepare for online publishing. At UCI I was recruited from the Department of Microbiology and Molecular Genetics to the Department of Biological Chemistry where I served as Chair from 1997 to 2005. During that time the department more than doubled and recruited a number of outstanding scientists. I have served as the founding Director of the UCI Genomics and High Throughput Facility (GHTF, previously DNA and Protein Microarray Facility) since 1999. In this capacity I work closely with the Facility Manager, Robert Chadwick, Ph.D., to promote access to new technologies to campus researchers through a variety of venues. We provide Affymetrix genechip analysis of current types, Illumina HiSeq 2000 next generation sequencing, and will shortly offer Applied Biosystems Ion Torrent third generation sequencing. I am currently serving as Associate Director of the UCI Institute for Genomics and Bioinformatics (Director, P. Baldi) and in this capacity work with a group of over twenty very talented graduate students that are participating in interdisciplinary training in the computational and natural sciences supported by a grant from the National Library of Medicine. We work through the Institute to develop interdisciplinary programs, seminars and workshops on the campus. My vision for the GHTF is that it serves as a platform for introducing new technologies to the academic research community of students, postdoctoral fellows and faculty, and in so doing makes new technology affordable and enables early use of emerging technologies. This has had a positive impact on Cancer Center researchers over the past ten years. PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Meyskens, Frank L. 5P30CA062203-17 B. Positions and Honors Positions and Employment 1980-1982 Damon Runyon Postdoctoral Fellow, Dept. Genetics, Washington University School of Medicine, St. Louis, MO, sponsor - Maynard Olson 1982-1983 Research Associate, Department of Genetics, Washington University, St. Louis, MO 1984-1990 Assistant Professor, Dept. Microbiology and Molecular Genetics, University of California, Irvine 1990-1994 Associate Professor, Dept. Microbiology and Molecular Genetics, University of California, Irvine 1994Professor, Dept. Microbiology and Molecular Genetics, University of California, Irvine 1997Professor, Dept. Biological Chemistry, University of California, Irvine 1997-2005 Chair, University of California, Irvine, Dept. of Biological Chemistry; 1999Director, UCI Genomics High-Throughput Facility (1999-2009 UCI DNA and Protein MicroArray Facility) 2008Associate Director, UCI Institute of Genomics and Bioinformatics 2009Member, California HIV Research Program Board Professional Memberships 2002American Association for the Advancement of Science 2002American Society of Microbiology 2002Genetics Society of America 2002American Society for Biochemistry and Molecular Biology National Service (selected) Study section and review panels 1993-1997 Member, Genetics Study Section, National Institutes of Health 1999 Ad hoc Member, NCI Study section on Molecular Classification of Tumors 1998-2003 Member, National Cancer Institute, Board of Scientific Counselors 2000, 2005 Reviewer, HHMI International Grants to Baltics, Central and Eastern European and Former Soviet Union 2005 Reviewer, National Technology Centers for Networks and Pathways, Roadmap Initiative 2006 Ad hoc member, NSF Genetics Study Section 2007 Ad hoc member, NIH MGA Study Section 2007 Ad Hoc Reviewer, Israeli Science Foundation 2007 Ad hoc member, NSF Genetics Study Section 2008 Member, review panel, University of Illinois, Chicago, Biology and Biochemistry Programs 2011 Ad Hoc Reviewer NIH Innovation Awards Editorial boards and reviewer 1994-2001 Member, Editorial Board: Molecular and Cellular Biology 1999-2007 Associate Editor, Genetics 2006-2008 Genetics, Chair, Senior Editors 2009Member, Editorial Board, Mobile DNA Reviewer: Current Biology; Eukaryotic Cell; Genetics; Genes and Development; Genome Research; Journal of Biological Chemistry; Journal of Virology; Molecular and Cellular Biology; Molecular Cell; Nucleic Acids Research; PLoS Genetics; Proc. Natl. Acad. Sci. USA;Traffic Meeting organizer 1995 Co-organizer, West Coast Retrovirus Meeting 1996 Co-organizer, Keystone Symposium on Transposition and Site-Specific Recombination 2003 Co-organizer, Cold Spring Harbor Retrovirus Meeting 2010 Organizer UCI Mobile DNA Mini-symposium 2011 Organizer UCI HTS to P4 Medicine Mini-Symposium PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Honors 1992 2003 2007 Meyskens, Frank L. 5P30CA062203-17 UCI School of Medicine Research Associates' Award, $10,000 American Academy of Microbiology (elected Fellow) American Association for the Advancement of Science (elected Fellow) C. Publications Most relevant recent publications 1. Irwin, B., Aye, M., Baldi, P., Beliakova-Bethell, N., Cheng, H., Dou, Y., et al. (2005). Retroviruses and yeast retrotransposons use overlapping sets of host genes. Genome Res., 15(5):641-54. PMCID: PMC1088292. 2. Kuznetsov, Y.G., Zhang, M., Menees, T.M., McPherson, A., Sandmeyer, S. (2005). Investigation by atomic force microscopy of the structure of Ty3 retrotransposon particles. J Virol., 79(13):8032-45. PMCID: PMC1143757. 3. Beliakova-Bethell, N., Beckham, C., Giddings, T.H. Jr., Winey, M., Parker, R., Sandmeyer, S. (2006). Virus-like particles of the Ty3 retrotransposon assemble in association with P-body components. RNA, 12(1):94-101. PMCID: PMC1370889. 4. Larsen, L.S., Beliakova-Bethell, N., Bilanchone, V., Zhang, M., Lamsa, A., Dasilva, R., et al. (2008). Ty3 nucleocapsid controls localization of particle assembly. J Virol., 82(5):2501-14. PMCID: PMC2258933. 5. Sandmeyer, S.B. and Clemens, K.A.C. (2010). Function of nucleocapsid in yeast Ty3 retrotransposition, Special Issue on RNA Chaperones and Helicases, RNA Biology, 7:642-654. *Contributed equally. Additional recent publications relevant to the field (in chronological order) 1. Hansen, L.J., Chalker, D.L., Sandmeyer, S.B. (1988). Ty3, a yeast retrotransposon associated with tRNA genes, has homology to animal retroviruses. Mol Cell Biol., 8(12):5245-56. PMCID: PMC365627. 2. Hansen, L.J., Chalker, D.L., Orlinsky, K.J., Sandmeyer, S.B. (1992). Ty3 GAG3 and POL3 genes encode the components of intracellular particles. J Virol., 66(3):1414-24. PMCID: PMC240865. 3. Chalker, D.L., Sandmeyer, S.B. (1992). Ty3 integrates within the region of RNA polymerase III transcription initiation. Genes Dev., 6(1):117-28. 4. Kinsey, P.T., Sandmeyer, S.B. (1995). Ty3 transposes in mating populations of yeast: a novel transposition assay for Ty3. Genetics., 139(1):81-94. PMCID: PMC1206350. 5. Kirchner, J., Connolly, C.M., Sandmeyer, S.B. (1995). Requirement of RNA polymerase III transcription factors for in vitro position-specific integration of a retroviruslike element. Science.267(5203):1488-91. 6. Menees, T.M., Sandmeyer, S.B. (1996). Cellular stress inhibits transposition of the yeast retrovirus-like element Ty3 by a ubiquitin-dependent block of virus-like particle formation. Proc Natl Acad Sci U S A.93(11):5629-34. PMCID: PMC39299. 7. Yieh, L., Kassavetis, G., Geiduschek, E.P., Sandmeyer, S.B. (2000). The Brf and TATA-binding protein subunits of the RNA polymerase III transcription factor IIIB mediate position-specific integration of the gypsy-like element, Ty3. J Biol Chem., 275(38):29800-7. 8. Larsen, L.S., Zhang, M., Beliakova-Bethell, N., Bilanchone, V., Lamsa, A., Nagashima, K., et al. (2007). Ty3 capsid mutations reveal early and late functions of the amino-terminal domain. J Virol., 81(13):695772. PMCID: PMC1933270. 9. Fang, F., Salmon, K., Shen, M., Aeling, K., Ito, E., Irwin, B., Tran, U., Hatfield, G.W., Da Silva, N.*, and Sandmeyer, S.* (2011). A combinatorial vector set for metabolic engineering in Saccharomyces cerevisiae. Yeast 28:123-136. 10. Christiansen, K., Larsen, L.Z., Zhang, M., Kuznetsov, Y., Bilanchone, V., Beliakova-Bethell, N., Randall, A., DaSilva, R., Nagashima, K., McPherson, A., Baldi, P. and Sandmeyer, S.B. (2011). Ty3 spacer controls intracellular condensation and uncoating. J. Virol., (Epub Jan26; PMID: 21270167; doi:10.1128/JVI.0105510). Patents: Position-Specific Endonuclease and Method of Using Same U.S. Serial Numbers 5,292,662 and 5,482,853 PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page Program Director/Principal Investigator (Last, First, Middle): Meyskens, Frank L. 5P30CA062203-17 D. Research support Ongoing research support 5P30CA062203-16 Meyskens (PI) 02/01/09-01/31/14 NIH/NCI University of California Irvine Cancer Center Support Grant Infrastructure and Research award to support cancer research at UC Irvine and beyond. Role: Shared Resource Director for UCI Genomics/High-throughput Facility R01 GM 33281-25 Sandmeyer (PI) 04/01/10-03/31/14 NIH Ty3 Viruslike particle morphogenesis and host interactions. This project is to identify host genes that support or antagonize Ty3 replication and to understand the molecular mechanisms underlying those effects. (The current application is the renewal of this award.) This has been the major source of support so the accomplishments are summarized in the personal statement. Role: PI #813570 Shanks (PI) 09/01/08-08/31/13 Host Institution University of Iowa Center for Biorenewable Chemicals This is an interdisciplinary project to use biosynthetic pathways in E. coli and S. cerevisiae to produce intermediates for industrial applications. The goal of the work in yeast in which the Sandmeyer laboratory is involved is to develop methods for production of short chain (<16 C) fatty acids in S. cerevisae. This project has enabled work generally in the laboratory as we have developed reagents for genetic manipulation of yeast in the course of this work. Completed research support Administrative supplement ($125K) for GM33281-24 (see above). This supplement was to further support accomplishment of the aims of the original grant. MCB-0450159 03/15/05 - 02/29/09 NSF tDNA Genes and Genetic Mobility in S. cerevisiae This project was to investigate the interaction between the Ty3 integrase and preintegration complex and transcription factors bound to the Ty3 target pol III transcribed genes and to map tRNA gene targets used in vivo. Accomplishments from this work were finished during an extension and are now being written up. Among the most exciting were development of a completely recombinant in vitro integration system (integrase and a single fusion targeting protein) and high throughput sequence analysis of Ty3 integration sites in collaboration with Johnston and Mitra at Washington University with Baldi lab (UCI) performing bioinformatic analysis. CODA-42397 Hatfield (PI) 09/01/07 – 08/31/09 CODA Genomics Inc. Optomized Heterologous Pathways for Ethanol Production in Yeast This was a collaborative interdisciplinary program supported by matching corporate and state funds. The goal of the project was to optimize expression in yeast of genes involved in xylose and arabinose metabolism in order to develop methodology for production of biofuels. NIH Shared Instrumentation Grant Sandmeyer (PI) High Throughput DNA Sequencer As Director of the UCI Genomics and High Throughput Facility I applied with the help of twenty colleagues for this grant. The sequencer is operational. PHS 398/2590 (Rev. 06/09) Page Biographical Sketch Format Page