Program Director/Principal Investigator (Last, First, Middle): Church, George, M. BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Church, George, M., PhD. eRA COMMONS USER NAME (credential, e.g., agency login) Professor GCHURCH EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) INSTITUTION AND LOCATION DEGREE (if applicable) YEAR(s) B.A. PhD. 1974 1984 Duke University, Durham, NC Harvard University, Cambridge, MA FIELD OF STUDY Zoology & Chem. Biochem. & Mol. Biol. A. Personal Statement: The goal of our part of the proposed research is to develop enabling technology for large-scale de novo synthesis of yeast chromosomes from oligonucleotides arrays. Specifically, we plan to focus on selections and counter-selections for metabolic pathways functioning in humans or producing inhibitors of human proteins. Our group has pioneered the use of oligo arrays for synthetic biology [15] as well as automated changes in living genomes [5], “next-generation” sequencing [2,6,14], computer aided metabolic design [9], selection and lab evolution [1,5,14]. From my thesis to the present I have worked on yeast [13] and human [7,11] biology using novel genetic technologies. Translation of technologies into clinical and commercial sector has been a priority (e.g. co-initiating metabolic-engineering companies LS9, Gen9, Joule, and Genomatica). I have been a part of the synthetic biology community since the first iGEM in 2004 and first SynBERC consortium in 2005. B. Positions and Honors: 1984 Scientist, Biogen Research Corporation, Cambridge, MA 1985-1986 Research Fellow, Anatomy, Univ. Calif., San Francisco, CA 1986-1998 Assistant/Associate Professor of Genetics, Harvard Medical School, Boston, MA 1997-present Director of the Lipper Center for Computational Genetics, Boston, MA 1998-present Professor of Genetics, Harvard Medical School, Boston, MA 2002-present Director of the Harvard/MIT DOE Genomes-to-Life Center 2004-present Director of the Harvard/MIT/WashU NHGRI CEGS 2006-present Senior Associate of Broad Inst. of Harvard & MIT (1990 Genome Center Co-founder) Honors, Awards, & Scientific Memberships: 1974-1975 National Science Foundation Predoctoral Fellow 1985-1986 Life Sciences Research Foundation Fellow 1976 National Science Foundation Program Project Grant Review Committee 1986-1997 Howard Hughes Medical Institute 1988,1992,1994 Department of Energy Genome Project Grant Review Committee 1990 NIH Genome Study Section Grant Review 1990 Co-founder of MIT, Stanford, & GTC Genome Sequencing Centers 1994-1997 National Center for Human Genome Research Review Committee 2001-present NIH BISTI, Pioneer, grant review committees, NHLBI BEE, NAS committees Editorial Boards Nature/EMBO-MSB, Genome Biology, Omics, BioMedNet Editorial Reviewer Nature (&NG, NB), Science, PNAS, Genome Research, NAR Scientific Boards: LS9, 23andme, Knome, Genomatica, JouleBio, CompleteGenomics, Sigma-Aldrich, Halcyon 2008 World Economic Forum Technology Pioneer Awards (LS9 & 23andme) 2009 American Society for Microbiology Biotechnology Research Award PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page Program Director / Principal Investigator: Church, George M. C. Selected peer-reviewed publications. (also see http://arep.med.harvard.edu) 1. Sommer MOA, Church GM, Dantas G (2010) A functional metagenomic approach for expanding the synthetic biology toolbox for biomass conversion Nature EMBO MSB in press. 2. Drmanac R, et al. (2010) Human Genome Sequencing Using Unchained Base Reads on Self-assembling DNA Nanoarrays. Science 327(5961):78-81 3. Sommer MO, Dantas G, Church GM. (2009) Functional Characterization of the Antibiotic Resistance Reservoir in the Human Microflora. Science Aug 28; 325 (5944) 1128 - 1131 4. Friedland AE, Lu TK, Wang X, Shi D, Church GM, Collins J (2009) Synthetic Gene Networks that Count. Science. Jun 14; 324(5931):1199-202. 5. Wang HH, Isaacs FJ, Carr PA, Sun ZZ, Xu G, Forest CR, Church GM (2009) Programming cells by multiplex genome engineering and accelerated evolution. Nature. Jul 26; 460(7257):894-8. 6. Li JB, Levanon EY, Yoon J-K, Aach J, Xie B, LeProust E, Zhang K, Gao Y, Church GM (2009) Genomewide Identification of Human RNA Editing Sites by Massively Parallel DNA Capturing and Sequencing. Science. Jun 14; 324(5931):1210-3. 7. Sullivan GJ, Hay DC, Park IH, Fletcher J, Hannoun Z, Payne CM, Dalgetty D, Black JR, Ross J, Samuel K, Wang G, Daley GQ, Lee JH, Church GM, Forbes SJ, Iredale JP, Wilmut I (2010 Generation of Functional Human Hepatic Endoderm from Human iPS cells. Hepatology Jan;51(1):329-35. 8. Tolonen A, Chilaka AC, Church GM (2009) Targeted gene inactivation in Clostridium phytofermentans shows that cellulose degradation requires the family 9 hydrolase Cphy3367.Mol Microbiol Dec;74(6):1300-13. 9. Lun DS, Rockwell G, Guido NJ, Baym M, Kelner JA, Galagan JE, Church GM (2009) Large-Scale Identification of Genetic Design Strategies using Local Search. Nature EMBO MSB 5:296. 10. Zhang K, Li JB, Gao Y, Egli D, Xie B, Lee JH, Aach J, LeProust E, Eggan K, Church GM (2009) Digital RNA Allelotyping Reveals Tissue-specific and Allele-specific Gene Expression in Human. Nature Methods Aug;6(8):613-8. 11. Lee J, Park IH, Gao Y, Li JB, Li Z, Daley G, Zhang K, Church GM (2009) A Robust Approach to Identifying Tissue-specific Gene Expression Regulatory Variants Using Personalized Human Induced Pluripotent Stem Cells. PLoS Genetics Nov;5(11):e1000718. PMC2766639 12. Carr P, Church GM (2009) Genome Engineering. Nature Biotech. Dec;27(12):1151-62. 13. Snitkin ES, Dudley AM, Janse DM, Wong K, Church GM, Daniel Segre D (Sep 2008). Model-driven analysis of experimentally determined growth phenotypes for 465 yeast gene deletion mutants under 16 different conditions. Genome Biology 9:R140. 14. Shendure J, Porreca GJ, Reppas NB, Lin X, McCutcheon JP, Rosenbaum AM, Wang MD , Zhang K, Mitra RD, Church GM (2005) Accurate Multiplex Polony Sequencing of an Evolved Bacterial Genome Science 309(5741):1728-32. 15. Tian J, Gong H, Sheng N, Zhou X, Gulari E, Gao X, Church G. (2004) Accurate multiplex gene synthesis from programmable DNA microchips. Nature. 2004 Dec 23;432(7020):1050-4. D. Research Support: Ongoing: DE-FG02-03ER63445 (GTL) 2/01/03 – 11/30/11 DOE-GTL PI: George Church Lab Title: Microbial Ecology, Proteogenomics & Computational Optima Our role in this Project is to develop analytic and synthetic biology tools for metabolic engineering 1P50 HG005550 (CEGS) NIH- NHGRI 9/13/10-07/31/2015 PI: George Church Title: "Center for Causal Transcriptional Consequences of Human Genetic Variation" Role: The Center for Transcriptional Consequences of Human Genetic Variation (CTCHGV) will develop innovative and powerful genetic engineering methods and use them to identify genetic variations that causally control gene transcription levels. PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page Program Director / Principal Investigator: Church, George M. SA5283-11210 (NSF) 7/01/06 – 6/30/11 PI: Jay Keasling (UC Berkeley) Title: Synthetic Biology Engineering Research Center (SynBERC) Our role is to develop synthetic bacterial genome “chassis” for safe use in mammals W911NF-08-1-0254 (DARPA) 6/27/08 – 1/31/11 PI: Neil Gershenfeld (MIT) Title: Milli-Biology: Programmed Assembly of Engineered Materials RO1 HL 094963- 01 (NHLBI) 9/30/08 - 6/30/11 (NCE) NIH - NHLBI PI: George Church Title: Targeted 2nd generation sequencing in phenotyped Framingham & PGP populations Goal: To develop, demonstrate, and validate a pipeline for high-throughput, low-cost targeted resequencing of all human exons based on next-generation (gen2) sequencing techniques in support of the long term goal of enabling sequencing to be used routinely to characterize genotypes and genetic variation in genome-wide medical targets for large populations of individuals AG-SS-2084-08 (Ellison) 11/01/08 -9/30/12 The Ellison Medical Foundation PI: George Church Title: Establishment and Functional Characterization of a Large DNA Fragment Resource from the Long-lived Naked Mole-Rat for Comparison with Mice. Goal: The identification and characterization of naked mole-rat genes that contributed to the evolution of a long lifespan in this species. RC2 HG005592 (NHGRI) 9/30/09-07/31/11 NIH-NHGRI – (Halcyon) PI: George Church Title: Development of Electron Microscopy-based Nucleic Acid Polymer Sequencing Project: We aim to provide a comprehensive foundation for development of an ultra-low-cost, ultra-fast nucleic acid polymer sequencing technology based on single-atom resolution transmission electron microscopy (TEM) of heavy atom-labeled nucleic acid polymers. RC2HL102815 (NHLBI) 9/30/09-08/31/11 NIH- NHLBI PI: George Daley (CHB) Title: Comparative phenotypic, functional, and molecular analysis of ESC and iPSC ONRBAA09-001 (ONR) 4/01/10-03/31/13 Office of Naval Research PI: George Church Title: Multiplexed Pathway and Organism Engineering RC1 HG005482 (NCRR) 9/22/09-06/30/11 NIH/NCRR PI: Peter Park Title: Statistical Methods for Estimation of Copy Number from Next – Generation Sequencing ARPA- E grant (DOE) 7/01/10-06/30/13 DOE- DE-AR0000079 Title: Engineering a Bacterial Reverse Fuel Cell PI: Silver, Pamela A; Co-I: George Church PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page Program Director / Principal Investigator: Church, George M. OVERLAP: None Completed: P50 HG003170 (CEGS) 5/01/04 – 04/30/10 (NCE) NIH - NHGRI PI: George Church Title: Molecular and Genomic Imaging Center Our role is to develop polony technology for resequencing of DNA and RNA in stem cells P50 HG003170 (CEGS supplement) 9/18/09-08/31/10 NIH- NHGRI PI: George Church Title: Molecular and Genomic Imaging Center Role: The goal of this request for supplemental funding for our Molecular and Genomic Imaging CEGS (MGIC) is further development of MGIC initiatives focused on single cell and splice isoform analysis along with enabling MGIC technology. PHS 398/2590 (Rev. 11/07) Page Biographical Sketch Format Page