The Jackson Laboratory PreDoc Program Opportunities for Predoctoral Research Aging, Bioinformatics, Computational Biology, Cardiovascular Biology, Development, Genomics, Hematology, Immunology/ Inflammation, Metabolism, Neurobiology, Research Tools, Stem Cells Welcome! The Jackson Laboratory (JAX), an international leader in mammalian genetics research, offers opportunities for Ph.D. research and training in cooperation with degree-granting academic programs. JAX researchers use the outstanding genetic and bioinformatics resources here to investigate normal biology and disease. Students take advantage of the research environment at JAX to conduct dissertation research, for lab rotations, and for short-term collaborative projects. In the following pages are scientific descriptions from Jackson Laboratory faculty who could sponsor predoctoral research. For more information about the predoctoral program, contact the office of Training and Education ([email protected]), or Mary Ann Handel, Ph.D., Scientific Director of the Predoctoral Program ([email protected]). 600 Main Street Bar Harbor, Maine 04609 USA 207-288-6000 www.jax.org Judith A. Blake, Ph.D. Associate Professor My research focuses on functional and comparative genome informatics. I work on the development of systems to integrate and analyse genetic, genomic and phenotypic information. I am one of the principal investigators of the Gene Ontology (GO) Consortium, an international effort to provide controlled structured vocabularies for molecular biology that serve as terminologies, classifications and ontologies to further data integration, analysis and reasoning. My interest in bio-ontologies stems as well from the work I do as a principal investigator with the Mouse Genome Informatics (MGI) project at The Jackson Laboratory. The MGI system is a model organism community database resource that provides integrated information about the genetics, genomics and phenotypes of the laboratory mouse. My current research projects combine bio-ontologies and database knowledge systems to analyse disease processes with the objective of discovering new molecular elements and pathways that contribute to particular pathologies such as respiratory diseases. Bult CJ, Eppig JT, Blake JA, Kadin JA, Richardson JE; the Mouse Genome Database Group. The Mouse Genome Database: Genotypes, Phenotypes, and Models of Human Disease. Nucleic Acids Res. 2013 Jan 1;41(D1):D885-D891. Drabkin HJ, Blake JA; Mouse Genome Informatics Database. Manual Gene Ontology annotation workflow at the Mouse Genome Informatics Database. Database (Oxford). 2012 Oct 29;2012:bas045. Bello SM, Richardson JE, Davis AP, Wiegers TC, Mattingly CJ, Dolan ME, Smith CL, Blake JA, Eppig JT. Disease model curation improvements at Mouse Genome Informatics. Database (Oxford). 2012 Mar 20;2012:bar063. Meehan TF, Carr CJ, Jay JJ, Bult CJ, Chesler EJ, Blake JA. Autism candidate genes via mouse phenomics. J Biomed Inform. 2011 Dec;44 Suppl 1:S5-11. Eppig JT, Blake JA, Bult CJ, Kadin JA, Richardson JE; Mouse Genome Database Group. The Mouse Genome Database (MGD): comprehensive resource for genetics and genomics of the laboratory mouse. Nucleic Acids Res. 2012 Jan;40(Database issue):D881-6. Aging • Bioinformatics • Computational Biology • Cardiovascular Biology • Development • Genomics • Genomics • Development Biology • Cardiovascular Biology • Computational Aging • Bioinformatics Cells • Stem Tools • Research • Neurobiology • Metabolism • Immunology/Inflammation Hematology 1 www.jax.org/research Ewelina Bolcun-Filas, Ph.D. Assistant Professor Germ cells are the only cell type that must endure extensive DNA damage in the form of programmed meiotic Double Strand Breaks (DSBs) during their normal development. Paradoxically, the absence of DSBs during meiosis as well as persisting unrepaired breaks are detrimental and typically result in meiotic arrest and infertility. Our research aims to understand the molecular mechanisms controlling the development of healthy gametes and how misregulation of these mechanisms can lead to reproductive disorders. In particular, we are interested in meiotic “quality checkpoints” operating in germ cells, which ensure that the correct and intact genetic information is transmitted to the next generation. The same checkpoint that monitors DSB repair during meiosis is responsible for high sensitivity of oocytes to cancer treatment. Chemo and radiation therapies can cause oocyte death and lead to premature ovarian failure and infertility. Disabling the key checkpoint kinase CHK2 preserved fertility in mice exposed to ionizing radiation, thus opening a new avenue for oncofertility research. Our goal is to further dissect the DNA damage response pathway in oocytes in hope to identify additional targets for fertility preservation therapies in cancer patients. Singh P, Schimenti JC, Bolcun-Filas E. A Mouse Geneticist’s Practical Guide to CRISPR Applications. Genetics. 2015 Jan:199(1) Bolcun-Filas, E., Rinaldi, V.D., White, M.E., Schimenti, J.C. Reversal of female infertility by Chk2 ablation reveals the oocyte DNA damage checkpoint pathway. Science. 2014 Jan 31; 343 (6170) Li XZ, Roy CK, Dong X, Bolcun-Filas E, Wang J, Han BW, Xu J, Moore MJ, Schimenti JC, Weng Z, Zamore PD. An ancient transcription factor initiates the burst of piRNA production during early meiosis in mouse testes. Mol Cell. 2013 Apr 11;50(1) Bolcun-Filas E, Schimenti JC. Genetics of meiosis and recombination in mice. Int Rev Cell Mol Biol. 2012 Li XC, Bolcun-Filas E, Schimenti JC. Genetic evidence that synaptonemal complex axial elements govern recombination pathway choice in mice. Genetics. 2011 Sep;189(1) Bolcun-Filas E, Bannister LA, Barash A, Schimenti KJ, Hartford SA, Eppig JJ, Handel MA, Shen L, Schimenti JC. A-MYB (MYBL1) transcription factor is a master regulator of male meiosis. Development. 2011 Aug;138(15) Wojtasz L, Daniel K, Roig I, Bolcun-Filas E, Xu H, Boonsanay V, Eckmann CR, Cooke HJ, Jasin M, Keeney S, McKay MJ, Toth A. Mouse HORMAD1 and HORMAD2, two conserved meiotic chromosomal proteins, are depleted from synapsed chromosome axes with the help of TRIP13 AAA-ATPase. PLoS Genet. 2009 Oct;5(10) Bolcun-Filas E, Hall E, Speed R, Taggart M, Grey C, de Massy B, Benavente R, Cooke HJ. Mutation of the mouse Syce1 gene disrupts synapsis and suggests a link between synaptonemal complex structural components and DNA repair. PLoS Genet. 2009 Apr;5(4). Hamer G, Wang H, Bolcun-Filas E, Cooke HJ, Benavente R, Hoog C. Progression of meiotic recombination requires structural maturation of the central element of the synaptonemal complex. J Cell Sci. 2008 Aug 1;121. Aging • Bioinformatics • Computational Biology • Cardiovascular Biology • Development • Genomics • Genomics • Development Biology • Cardiovascular Biology • Computational Aging • Bioinformatics Cells • Stem Tools • Research • Neurobiology • Metabolism • Immunology/Inflammation Hematology www.jax.org/research 2 Robert Braun, Ph.D. Professor Geneticists measure time in generations and celebrate immortality with reproductive success. My lab is driven by a passion to understand the cell biological basis of gamete (sperm and egg) development. We study how germline stem cells balance self-renewal with differentiation. Stem cell self- renewal at the expense of differentiation can cause germ cell tumors while differentiation at the expense of self-renewal can cause sterility. Our long-term goal is to understand the mechanisms that regulate germline stem cell fate. Other research interests include understanding the molecular function of the hormone testosterone in spermatogenesis. Our work has revealed that specialized tight junctions between Sertoli cells, which are integral to the blood/testis barrier, are regulated by testosterone. We are studying how germ cells pass through these tight junctions without compromising barrier function. We are also investigating molecular mechanisms of translational regulation—a major form of gene regulation in both male and female germ cells—during spermatogenesis. We use both forward and reverse genetics to identify the genes involved. Phenotypic analysis includes microscopy, biochemistry and cell physiology. Greenlee AR, Shiao MS, Snyder E, Buaas FW, Gu T, Stearns TM, Sharma M, Murchison EP, Puente GC, Braun RE. 2012. Deregulated sex chromosome gene expression with male germ cell-specific loss of Dicer1.PLoS One 7: e46359. Smith BE, Braun RE. Germ cell migration across Sertoli cell tight junctions. Science. 2012 Nov 9;338(6108):798-802. Gu T, Buaas FW, Simons AK, Ackert-Bicknell CL, Braun RE, Hibbs MA. 2011. Canonical A-to-I and C-to-U RNA editing is enriched at 3’ UTRs and microRNA target sites in multiple mouse tissues. PLoS One 7: e33720. Navarro VM, Gottsch ML, Wu M, Garcia-Galiano D, Hobbs SJ, Bosch MA, Pinilla L, Clifton DK, Dearth A, Ronnekleiv OK, Braun RE, Palmiter RD, Tena- Sempere M, Alreja M, Steiner RA. 2011. Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 152: 4265-4275. PMCID: Meng J, Greenlee AR, Taub CJ, Braun RE. 2011. Sertoli cell-specific deletion of the androgen receptor compromises testicular immune privilege in mice. Biol Reprod 85: 254-260. Aging • Bioinformatics • Computational Biology • Cardiovascular Biology • Development • Genomics • Genomics • Development Biology • Cardiovascular Biology • Computational Aging • Bioinformatics Cells • Stem Tools • Research • Neurobiology • Metabolism • Immunology/Inflammation Hematology 3 www.jax.org/research