CONCLUDING COMMENTS

At this point, it should be evident that we have a remarkable team effort that is integrated and focused on the key issues -- In order to engineer cells in ecosystems of energy relevance (and protect them from pollution), we need to model whole systems with explicit recognition of the central role of "optimality". In order to do that modeling, we need detailed and comprehensive data on the actual metabolism of individual cells, including cells, which do not replicate rapidly. We need to escape the "model organisms" including ways to genomically manipulate and measure whole populations of cells without the restrictions of colony purification. For some methods we also need populations of nearly identical (synchronized) cell states. To determine the constraints on each cell we need models and measures integrating the full metabolism and replication of the cells. The technologies described here are novel, cutting through previous impasses, yet down-to-earth in terms of feasibility and rapid start. We have tried to be frugal in numerous ways, focusing most of the costs on the most abundant, and initially the smallest genomes as well as employing novel, cost-effective technologies.

 

MANAGEMENT PLAN

"The responsibility of and relationship between all participating institutions and investigators, a strategy for maximizing communication and exchange of information between investigators, a data and information management plan, and project milestones."

The ultimate responsibility for milestones, communication, coordination, and budgets lies with the Harvard Center for Computational Genetics (HCCG) and the PI, George Church. HCCG has been operational since 1997 with origin earlier in the first extramural DOE HGP technology center in 1987. Since then it has participated in over 50 academic collaborations including initiating three of the original HGP sequencing centers, co-managing several Boston functional genomics resources. It has over a dozen technology transfers and successful distribution of hundreds of strain and software requests. It has one of the first Internet sites in biology (FTP in 1987, HTTP in 1993) on which scientific and organizational communications are updated daily. These days some of the most challenging management issues deal with rapidly changing information technologies and the diverse set of highly intellectual talents required for true integration. This is a very different management task than running a technician-based sequencing center or large relational database maintenance. Our center focus has always been technology development and data-model integration. In recognition of this we have just been awarded the only PhRMA-Foundation. Center for Excellence in Integration of Genomics and Informatics (CEIGI).

We are very fortunate to be able to have a team of experts on each of these organisms and technologies all within walking distance (more typically shuttle bus or car), at five world-class institutions (Harvard Medical School, Harvard CGR, MIT, BWH, and MGH). So communication has been and will continue to be efficient and frequent. In addition to the twice-weekly HCCG meetings to which all collaborators are invited, we will hold monthly meetings specifically dedicated to integrating GTL components. We also will integrate our GTL project with other GTL centers and the potentially relevant (but so far non-overlapping) DARPA BioSPICE project by way of annual meetings organized by DOE and DARPA. Our group will be one of the few participating in both programs and would thus help bridge and coordinate.

We have established an external advisory committee consisting of Andrew Link (Vanderbilt, Goal 1), Saeed Tavazoie (Princeton, Goal 2), Colleen Cavanaugh (Harvard Goal 3), Bernard Palsson (UCSD, Goal 4). These four are chosen as people who, based on our past experience, are sufficiently motivated to look deeply into our project progress and plan adjustments. We expect that the oversight will be by phone, email and at international meetings so as to minimize the impact on the valued time of these four experts. Obviously our advisors will not be not limited to this set of four, but this set agree in advance to be more proactive and critical on this project than our other colleagues.

 

The details of the tasks behind the milestones are mentioned in main text for each of the goals.

The timelines for those milestones is below.

Abbreviations: 1=Prochlorococcus, 2=Caulobacter, 3=Pseudomonas,

4= Diverse genera, 5= Technology development

Goals Years: 2003 2004 2005 2006 2007

(1a) Proteogenomic Mapping 1 1 2 3 1,2,3

(1b) Quantitative Interaction Proteomics 5 1 2 3 1,2,3

(1c) Proteomic Cellular Deconvolution 5 1 2 3 1,2,3

(2a) RNA network in controlled conditions 1 2,3 1,2,3 - -

(2b) Regulatory motif combinations 1 2,3 - 1,2,3 -

(3a) Study the in situ microdiversity 5 1,4 1,4 4 4,5

(3b.i) Functional Diversity Arrays 5 5,4 5,4 5,4 5,4

(3b.ii) Single Cell Activity Multiplexing 5 5,4 5,4 5,4 5,4

(3c) RNA in situ 5 5,3 3 5 3,4

(3d) Transposon arrays 5,3 1 1 5 4

(4a) MPA for Goal 2. 5 1 2 3 1,2,3

(4b) Adding genes with MPA (3a) 5 - 3 2 1

(4c) Ecosystem FBA (3b) - 5,1,3 - 4 5

(4d) Compartmental FBA & MPA (3c) 5 1 1 3 2,4

(4e) 4D cell division model 5 1 5 2 1,2,3

There are relatively few crucial dependencies, but there are many beneficial interconnections. For example, goal 4c will greatly benefit from goals 3a,b so goal 4c is delayed correspondingly. Goal 4e will benefit from goal 1c. Based on past experience, we anticipate that significant changes will occur due the the positive effects of technology development in our group and others. The milestones will typically entail peer-reviewed publications, patents, and web-delivered data/software.

 

 

BIBLIOGRAPHY Names of PIs for this grant are in bold; asterisks (*) in the text refer to these papers, some of which are included in the appendices rather than repeat their detailed content and protocols in the main text of this proposal.

RELEVANT GENOME SEQUENCES:

Prochlorococcus MED4: 1.658 Mbp

Prochlorococcus MIT9313: 2.4 Mb

Pseudomonas fluorescens Pf0-1: 5.5 Mbp

Pseudomonas putida KT2440: 6.1 Mbp

Pseudomonas putida PRS1: 6.1 Mbp

Pseudomonas aeruginosa PA01 *: 6.264 Mbp (Stover et al. 2000)

Pseudomonas aeruginosa PA14: 6 Mbp

Caulobacter crescentus: 4.016 Mbp (Nierman 2001)

Methanobacterium thermoautropicum * 1.751 Mbp (Smith et al. 1997)

Mycoplasma pneumoniae: 0.816 Mbp (Dandekar et al. 2000)

http://bahama.jgi-psf.org/prod/bin/microbes/pmarmit/home.pmarmit.cgi

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http://www.jgi.doe.gov/JGI_microbial/html/Pseudomonas/pseudo_homepage.html

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Wolters DA, Washburn MP, Yates JR 3rd. Anal Chem 2001 Dec 1;73(23):5683-90 An automated multidimensional protein identification technology for shotgun proteomics.

Wright, M and Church,GM (2002) An Open-source Oligonucleotide Microarray Probe Standard for Human and Mouse. Submitted to Nature Biotech.

Wyrick JJ, Aparicio JG, Chen T, Barnett JD, Jennings EG, Young RA, Bell SP, Aparicio OM. Science 2001 Dec 14;294(5550):2357-60 Genome-wide distribution of ORC and MCM proteins in S. cerevisiae: high-resolution mapping of replication origins.

Yang, Z. and J.P. Bielawski. 2000. Statistical methods for detecting molecular adaptation. Trends Ecol. Evol. 15: 496-503.

Yang, Z. and R. Nielsen. 1998. Synonymous and nonsynonymous rate variation in nuclear genes of mammals. J. Mol. Evol. 46: 409-418.

Zehr JP, Waterbury JB, Turner PJ, Montoya JP, Omoregie E, Steward GF, Hansen A, Karl DM. Unicellular cyanobacteria fix N2 in the subtropical North Pacific Ocean. Nature. 2001 Aug 9;412(6847):635-8.

Zhang, J. 1999. Performance of likelihood ratio tests of evolutionary hypotheses under inadequate substitution models. Mol. Biol. Evol. 16: 868-875.

Zhu,Z, Pilpel, Y, and Church, GM (2002) Computational Identification of Transcription Factor Binding Sites via a Transcription-factor-centric Clustering (TFCC) Algorithm. J.Mol. Biol 318: 71-81.

Zinser, E.R. and R. Kolter. 1999. Mutations Enhancing Amino Acid Catabolism Confer a Growth Advantage in Stationary Phase. J. Bacteriol. 181:5800-5807.

Zinser, E.R. and R. Kolter. 2000. Prolonged stationary-phase incubation selects for lrp mutations in Escherichia coli K-12. J. Bacteriol. 182:4361-4365.

 

BIOGRAPHICAL SKETCHES:

(In the summary below the goals and organisms listed after each name only indicate main writing responsibilities or past expertise, not intended to represent future limitations, since we are all enthusiastic about the integrative nature of the project)

Principal investigators:

George Church <church@whiz.med.harvard.edu>, Project Director, Goals 1-4, Diverse genera

Fred Ausubel <ausubel@frodo.mgh.harvard.edu>, Goals 2,3, Pseudomonas

Sallie (Penny) Chisholm <chisholm@MIT.EDU> Goals 2,3, Pseudomonas

Martin Polz <mpolz@MIT.EDU>, Goal 3, Diverse genera

Roberto Kolter <kolter@mbcrr.harvard.edu>, Goal 3, Pseudomonas

Raju Kucherlapati <rkucherlapati@rics.bwh.harvard.edu>, Goal 1

Collaborators (funded from other sources):

Steve Lory <stephen_lory@hms.harvard.edu>, Goals 2, 3, Pseudomonas

Steve Gygi <steven_gygi@hms.harvard.edu>, Goal 1, Saccharomyces

Mike Laub <laub@cgr.harvard.edu>, Goal 2, Caulobacter

 

Advisors:

Andrew Link <Andrew.Link@mcmail.vanderbilt.edu> Goal 1, Saccharomyces

Saeed Tavazoie <tavazoie@molbio.princeton.edu> Goal 2, Escherichia

Colleen Cavanaugh <ccavanaugh@oeb.harvard.edu> Goal 3, Diverse genera

Bernhard Palsson <bpalsson@be-research.ucsd.edu> Goal 4, Diverse genera

 

NAME

George M. Church

POSITION TITLE

Professor

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)

FIELD OF STUDY

Duke University, Durham, NC

B.A.

1974

Zoology & Chem.

Harvard University, Cambridge, MA

Ph.D.

1984

Biochem. & Mol. Biol.

Professional Experience:

1984 Scientist, Biogen Research Corporation, Cambridge, MA

1985-1986 Research Fellow, Anatomy, Univ. Calif., San Francisco

1986-1998 Assistant/Associate Professor of Genetics, Harvard Medical School

1997-present Director of the Lipper Center for Computational Genetics

1998-present Professor of Genetics, Harvard Medical School

Honors, Awards, and 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 Genome

Research Review Committee

1998-present Physiological Genomics

2001-present NIH BISTI & DOE Sloan Fellow grant review committees

Editorial Boards Functional & Integrative Genomics, Genome Biology, Omics, BioMedNet

Editorial Reviewer Nature (&NG,NB), Science, PNAS, Genome research, NAR

Scientific Boards GTC, GPC, Caliper, Longenity, EngeneOS, BeyondGenomics, Xeotron, Genomatica

Selected Recent Publications: (see also http://arep.med.harvard.edu)

Bulyk ML, Johnson PLF, Church GM. (2002) Nucleotides of transcription factor binding sites exert interdependent effects on the binding affinities of transcription factors. Nucleic Acids Research 30:1255-1261.

Weber, G, Jay Shendure, J, Tanenbaum, DM, Church GM, and Meyerson M (2002) Microbial sequence identification by computational subtraction of the human transcriptome. Nature Genetics 30(2):141-2.

Cohen, B, Pilpel,Y, Mitra, R, Church,GM (2002) Discrimination between paralogs using microarray analysis: Application to the Yap1p and Yap2p transcriptional networks. Proc. Nat. Acad. Sci. in press

Pilpel, Y, Sudarsanam, P and Church, GM (2001) Identifying regulatory networks by combinatorial analysis of promoter elements in S. cerevisiae. Nature Genetics 29(2):153-9.

Badarinarayana, V, Estep, PW, Shendure, J, Edwards, J, Tavazoie, S, Lam, F and Church, GM (2001) Selection analyses of insertional mutants using subgenic-resolution arrays; Nature Biotechnology 19: 1060-5.

Ge, H, Church, GM, Vidal, M (2001) Correlation between transcriptome and interactome data obtained from S. cerevisiae. Nature Genetics, Dec;29(4):482-6.

Ting Chen, Jacob D. Jaffe, George M. Church (2001) Algorithms for Identifying Protein Cross-links via Tandem Mass Spectrometry . J. Comp. Biol. 8(6):571-583.

Aach, J and Church, GM (2001) Aligning gene expression time series with time warping algorithms Bioinformatics 17:495-508.

Bulyk, ML, Choo, Y., Huang, X, and Church, G.M. (2001) Exploring DNA binding specificities of zinc fingers with DNA microarrays. Proc. Nat. Acad. Sci USA 98: 7158-7163.

Aach, J., Bulyk, ML., Church, GM, Comander, J, Derti, A. Shendure, J (2001) Computational comparison of two draft sequences of the human genome. Nature 409: 856-859.

Selinger, D., Cheung, K., Mei, R., Johanson, E.M., Richmond, C., Blattner, F.R., Lockhart, D., and Church, G.M. (2000) RNA expression analysis using a 30 base pair resolution. Escherichia coli genome array. Nature Biotechnology 18: 1262-7.

Jamshidi, N., Edwards, J.S., Church, G.M., Palsson, B.O. (2001) A computer model of human red blood cell metabolism. Bioinformatics 17: 286-287.

Livesey, F.J., Furukawa, T., Steffen, M.A., Church, G.M., and Cepko, C.L., (2000) Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx. Current Biology 10:301-310.

Hoehe, M.R. Kopke, K, Wendel,B, Rohde, K, Flachmeier, C, Kidd, KK, Berrettini,WH & Church, GM (2000) Sequence Variability and Candidate Gene Analysis in Complex Disease: Association of mu Opioid Receptor Gene Variation with Substance Dependence. Human Molec. Genetics 9: 2895-2908.

Cohen, B.A., Mitra, R.D., Hughes, J.D., and Church, G.M. (2000) A computational analysis of whole genome expression data reveals chromosomal domains of gene expression. Nature Genetics 26: 183-186.

Mcguire, A.M. and Church, G.M., (2000) Predicting regulons and their cis-regulatory motifs by comparative genomics. Nucleic Acids Research 28:4523-30.

Goldmark,J.P., Fazzio,T.G., Estep,P.W., Church,G.M., and Tsukiyama, T. (2000) The Isw2 chromatin remodeling complex represses early meiotic genes upon recruitment by Ume6p, Cell 103: 423.

Jelinsky, S.A., Estep, P., Church, G.M., Samson, L.D. (2000) Regulatory networks revealed by transcriptional profiling of damaged Saccharomyces cerevisiae cells: Rpn4 links base excision repair with proteasomes. Molecular and Cellular Biol. 20:8157-8167.

McGuire, A.M., Hughes, J.D., and Church, G.M. (2000) Conservation of DNA regulatory motifs and discovery of new motifs in microbial genomes. Genome Res. 10:744-57.

Johnson, J.M. and Church, G.M. (2000) Sequence determinants of non-catalytic ligand binding in the LacI/RbsB/SubI superfamily: Connecting structural and functions genomics. Proc. Nat. Acad. Sci USA 97:3965-70

Teichmann, S.A., Cothia, C., Church, G.M., Park, J. (2000) Fast assignment of protein structures to sequences using the intermediate sequence library PDB-ISL. Bioinformatics 16: 117-124.

Cheng, Y. and Church, G.M. (2000) Biclustering of expresssion data. ISMB 2000.

Chen, T., Kao, M., Tepel, M., Rush, J., and Church, G.M. A dynamic programming approach to de novo peptide sequencing via tandem mass-spectrometry (11th SIAM-ACM Symposium on Discrete Algorithms, SODA2000).

Hughes, J.D., Estep, P.W., Tavazoie, S. and Church, G.M. (2000) Computational identification of cis-regulatory elements associated with functionally coherent groups of genes in Saccharomyces cerevisiae. J. Molec. Biol. 296: 1205-1214.

Aach, J., Rindone, W., Church, G.M. (2000) Systematic management and analysis of yeast gene expression data.Genome Research 10: 431-445. ExpressDB.

biographical sketch

NAME

POSITION TITLE

Sallie W. Chisholm

McAfee Professor of Engineering

Professor of Biology

EDUCATION/TRAINING

INSTITUTION AND LOCATION

DEGREE

YEAR(s)

FIELD OF STUDY

Skidmore College, NY

B.S.

1969

Biology and Chemistry

SUNY Albany, NY

Ph.D.

1974

Biology

Scripps Institution of Oceanography, CA

Postdoc

1974-1976

Biological Oceanography

Professional Experience

1976-present Assistant to Full Professor, Department of Civil and Environmental Engineering
Massachusetts Institute of Technology

1993-present Joint Appointment, Department of Biology
Massachusetts Institute of Technology

1988-95 MIT Director, MIT/Woods Hole Joint Program in Oceanography and Oceanographic Engineering

1978-present Visiting Scientist, Biology Department
Woods Hole Oceanographic Institution

Honors and Awards

1998 Resident Scholar, Bellagio Study and Conference Center, Italy

1997 Guggenheim Fellow

1996 Fellow, American Geophysical Union

1993 Fellow, American Society of Microbiology
1993 Member, International Ecology Institute
1992 Fellow, American Academy of Arts and Sciences
1991 Rosenstiel Award in Ocean Sciences
1987-1989 Associate Chair, MIT Faculty
1980-1982 Doherty Professor of Ocean Utilization
1977-1978 Edgerton Assistant Professor

Relevant Publications (Total of 21 publications 1999-2002; relevant subset listed here):

2002 Saito, M. A., J. W. Moffett, S. W. Chisholm, and J. Waterbury. Cobalt Limitation and Uptake in Prochlorococcus. Limnol. Oceanogr. (in press)

2002 Moore, L R., A.F. Post, G. Rocap, and S.W. Chisholm Utilization of different nitrogen sources by the marine cyanobacteria, Prochlorococcus and Synechococcus. Limnol Oceanogr. (in press)

2002 Ting, C.S., G.Rocap, J. King, and S.W. Chisholm. Cyanobacterial photosynthesis in the oceans: Origins and significance of divergent light-harvesting strategies. Trends in Microbiol (in press).

2002 Mann, E.L., N. Ahlgren, J. W. Moffett, and S. W. Chisholm. Copper Toxicity and Cyanobacteria Ecology in the Sargasso Sea. Limnol. Oceanogr. (in press).

2002 Rocap, G. D. L. Distel, J. B. Waterbury and S. W. Chisholm. Resolution of Prochlorococcus and Synechococcus ecotypes using 16S-23S rDNA Internal Transcribed Spacer (ITS) sequences. Appl. Env. Microbiol.. 68(3): 1180-1191.

2001 Hess, W.R., G. Rocap, C. Ting, and S.W. Chisholm. The photosynthetic apparatus of Prochlorococcus: Insights through comparative genomics. Photosynthesis Research 70:53-71

2001 Ting CS, Rocap G, King J, Chisholm SW. Phycobiliprotein genes of the Marine Photosynthetic Prokaryote Prochlorococcus: Evidence for Rapid Evolution of Genetic Heterogeneity. Microbiology 2001; 147: 3171-3182

2001 DuRand, M.D., R.J. Olson, and S.W. Chisholm. Phytoplankton population dynamics at the Bermuda Atlantic Time-series Station in the Sargasso Sea. Deep-Sea Research II, 48(8-9), 1983-2003. 

2000 Mann, E. and S.W. Chisholm. Iron limits the cell division rate of Prochlorococcus in the Eastern Equatorial Pacific. Limnol. Oceanogr. 45:1067-1076

2000 Dusenberry, J.A., R.J. Olson, and S.W. Chisholm. Field observations of oceanic mixed layer dynamics and picophytoplankton photoacclimation. J. Mar. Sys. 24:221-232.

2000 Worden, A.Z. , S.W. Chisholm, and B.J. Binder. In situ hybridization of Prochlorococcus and Synechococcus (marine cyanobacteria) spp. with rRNA – targeted peptide nucleic acid probes. Appl. Env. Microbiol 66(1): 284-289.

1999 Rocap, G., L.R. Moore, and S.W. Chisholm. Molecular phylogeny of Prochlorococcus ecotypes. In: Marine Cyanobacteria and Related Organisms, L. Charpy and T. Larkam (eds). Bulletin de l’Institute Océanographique, Monaco, special issue N 19.  pp. 107-116.

1999 Moore, L. R. and S. W. Chisholm. Photophysiology of the marine cyanobacterium Prochlorococcus: Ecotypic differences among cultured isolates. Limnol. Oceanogr. 44(3)628-638.

1999 Ting C., Rocap G., King J., Chisholm S.W. Characterization of Phycoerythrin Genes in the Chlorophyll a2/b2-Containing Prokaryote, Prochlorococcus sp. MIT9303. In: (G. Garab, Ed.) Photosynthesis: Mechanisms and Effects, Vol. 1, Kluwer Academic Publishers, The Netherlands, pp. 225-228

1998 Urbach, E. and S.W. Chisholm. Genetic diversity in Prochlorococcus populations flow-cytometrically sorted from the Sargasso Sea and Gulf Stream. Limnol. Oceanogr. 43:1615-1630.

1998 Moore, L., Rocap, G., and Chisholm, S. Physiology and molecular phylogeny of coexisting Prochlorococcus ecotypes. Nature 393: 464-467

1998 Urbach, E., Scanlan, D.J., Distel, D.L., Waterbury, J.B. and Chisholm, S.W. (1998). Rapid diversification of marine picophytoplankton with dissimilar light-harvesting structures inferred from sequences of Prochlorococcus and Synechococcus (Cyanobacteria). J. Mol. Evol. 46:188-201.

1996 Binder, B.J., S.W. Chisholm, R.J. Olson, S.L. Frankel, and A.Z. Worden. Dynamics of Pico-phytoplankton, Ultra-Phytoplankton, and Bacteria in the Central Equatorial Pacific. Deep-Sea Res. II 43:907-931.

1995 Vaulot, D, D. Marie, R.J. Olson & S.W. Chisholm. Growth of Prochlorococcus, a Photosynthetic Prokaryote, in the Equatorial Pacific Ocean. Science 268:1480-1482.

1995 Moore, L.R, Goericke, R.E., Chisholm, S.W. Comparative Physiology of Synechococcus and Prochlorococcus: influence of light and temperature on growth, pigments, fluorescence and absorptive properties. Mar. Ecol. Prog. Ser. 116:259-275.

1994 Martin, J.A. & the IRONEX Group. Testing the iron hypothesis in ecosystems of the equatorial Pacific Ocean. Nature 371:123-148.

1992 Urbach, E. D. Robertson, and S.W. Chisholm. Multiple evolutionary origins of prochlorophytes within the cyanobacterial radiation. Nature 355:267-270.

1992 Chisholm, S.W., S.L. Frankel, R. Goericke, R.J. Olson, B.Palenik, J.B. Waterbury, L. West-Johnsrud, and E.R. Zettler. Prochlorococcus marinus nov. gen. nov. sp.: an oxyphototrophic marine prokaryote containing divinyl chlorophyll a and b. Arch. Microbiol. 157:297-300.

1988 Chisholm, S.W., R.J. Olson, E.R. Zettler, R. Goericke, J. Waterbury, and N. Welschmeyer. A novel free-living prochlorophyte abundant in the oceanic euphotic zone. Nature, 334(6180):340-343.

FF

BIOGRAPHICAL SKETCH

 

NAME

POSITION TITLE

Raju Kucherlapati

Professor

EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.)

institution and location

DEGREE

YEAR(s)

FIELD OF STUDY

(If applicable)

P.R. College, Kakinada, India

B.Sc.

1960

Biology

Andhra University, India

M.Sc.

1962

Genetics

University of Illinois, Urbana, IL

Ph.D.

1972

Genetics

 

Research and Professional Experience:

1967-72 Graduate Student, University of Illinois, Urbana, IL

1972-75 Postdoctoral Fellow, Yale University, New Haven, CT

1975-82 Assistant Professor, Department of Biochemical Sciences, Princeton University, Princeton, NJ

1982-89 Professor, Dept. of Genetics, University of Illinois College of Medicine, Chicago, IL

1989-2001 Professor and Chairman, Dept. of Molecular Genetics, Albert Einstein College of Medicine, NY

2001- Professor of Genetics and Medicine, Harvard Medical School, Boston, MA

2001- Scientific Director, Harvard-Partners Center for Genetics and Genomics

Honors: Pushpa Rangaswamy Iyengar Memorial Prize for standing first in class of 1962

Damon Runyon Memorial Cancer Research Fellowship, 1973-74

NIH Postdoctoral Fellowship, 1974-75

Member, NIH Biomedical Sciences Study Section, 1981-84

Member, NIH Mammalian Genetics Study Section, 1985-89

Co-organizer, Cold Spring Harbor Symposium: Intermediates in Genetic Recombination, 1988

Chairman, Gordon Research Conference on Molecular Genetics, 1989

Co-organizer, NIH Workshop: Applications of Homologous Recombination to Human Genetics, 1989

Co-organizer, Chromosome 12 Workshops #1, 2, 3 and 4, 1992-97

Member, Genome Research Review Committee, NCHGR, NIH, 1990-95

Member, Mental Retardation Review Committee, NICHD, NIH, 1995-97

Chairman, Mental Retardation Review Committee, NICHD, NIH, 1997-99

Member, National Advisory Council for Human Genome Research, NHGRI, NIH, 1998-

Publications:

  1. Kucherlapati, R., R. Tepper, A.G. Piperno and E. Reich. (1978) Modulation and mapping of a human plasminogen activator by cell fusion. Cell 15, 1331-1340.
  2. Kucherlapati, R. and S.I. Shin. (1979) Genetic control of tumorigenicity in interspecific mammalian cell hybrids. Cell 16, 639-648.
  3. Davies, R.L., S. Fuhrer-Krusi and R. Kucherlapati. (1982) Modulation of transfected gene expression mediated by changes in chromatin structure. Cell 31, 521-529.
  4. Roginski, R., A. Skoultchi, P. Henthorn, 0. Smithies, N. Hsiung and R. Kucherlapati. (1983) Coordinate modulation of transfected HSV thymidine kinase and human globin genes. Cell 35, 149-155.
  5. Smithies, 0., R.G. Gregg, S.S. Boggs, M.A. Koralewski and R.S. Kucherlapati. (1985) Insertion of DNA sequences into the human chromosomal Beta globin locus by homologous recombination. Nature 317, 230-234.
  6. Fodde, R., Edelmann, W., Yang, K., van Leeuwen, C., Carlson, C., Renault, B., Breukel, C., Alt, E., Lipkin, M., Meera Khan, P. and Kucherlapati, R. (1994) A Targeted Chain Termination Mutation in the Mouse Apc Gene Results in Multiple Intestinal
  7. Tumors. PNAS 91, 8969-8973.

 

 

 

 

 

 

 

 

 

  1. Krauter, K., Montgomery, K., Yoon, S.-J., LeBlanc-Straceski, J., Renault, B., Marondel, I., Herdman, V., Cupelli, L., Banks, A., Lieman, J., Menninger, J., Bray-Ward, P., Nadkarni, P., Weissenbach, J., Chumakov, I., Cohen, D., Miller, P., Ward, D. and Kucherlapati, R. (1995) A second generation YAC contig map of human chromosome 12. Nature 377: 321-333.
  2. Collins, J.E., Cole, C.G., Smink, L.J., Garrett, C.L., Leversha, M.A., Soderlund, C.A., Maslen, G.L., Everett, L.A., Rice, K.M., Coffey, A.J., Gregory, S., Gwilliam, R., Dunham, A., Davies, A.F., Hassock, S., Todd, C.M., Lehrach, H., Hulsebos, T.J.,M., Weissenbach, J., Morrow, B., Kucherlapati, R.S., Wadey, R., Scambler, P.J., Kim, U.-J., Simon, M.I., Carter, N.P., Durbin, R., Dumanski, J.P., Bentley, D.R. And Dunham, I. (1995) A high density YAC contig map of human chromosome 22. Nature 377, 367-371.
  3. Johnson, D.W., Berg, J.N., Baldwin, M.A., Gallione, C.J., Marondel, I., Yoon, S.-J., Stenzel, T.T., Speer, M., Pericak-Vance, M.A., Diamond, A., Guttmacher, A.E., Jackson, C.E., Attisano, L., Kucherlapati, R., Porteous, M.E.M. and Marchuk, D.A. (1996) Mutations in the activin receptor-like kinase 1 gene in hereditary haemorrhagic telangiectasia type 2. Nature Genet. 13:189-195.
  4. Edelmann, W., Cohen, P.E., Kane, M., Lau, K., Morrow, B., Bennett, S., Umar, A., Kunkel, T., Cattoretti, G., Chaganti, R., Pollard, J.W., Kolodner, R.D. and Kucherlapati, R. (1996) Meiotic pachytene arrest in MLH-1-deficient mice. Cell 85: 1125-1134.
  5. Liedtke, W., Edelmann, W., Bieri, P.L., Chiu, F.-C., Cowan, N.J., Kucherlapati, R. and Raine C.S. (1996) GFAP is necessary for the integrity of CNS white matter architecture and long-term maintenance of myelination. Neuron 17, 607-615.
  6. Basson, C.T., Bachinsky, D.R., Lin, R.C., Levi, T., Elkins, J.A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T.A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J.G. and Seidman, C.E. (1997) Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome. Nature Genet. 15, 30-35.
  7. Johnson, L., Greenbaum, D., Cichowski, K., Mercer, K., Murphy, E., Schmitt, E., Bronson, R.T., Umanoff, H., Edelmann, W., Kucherlapati, R. and Jacks, T. (1997) K-ras is an essential gene in the mouse with partial functional overlap with N-ras. Genes Devel. 11, 2468-2481.
  8. Edelmann, W., Yang, K., Umar, A., Heyer, J., Lau, K., Fan, K., Liedtke, W., Cohen, P.E., Kane, M.F., Lipford, J.R., Yu, N., Crouse, G.F., Pollard, J.W., Kunkel, T., Lipkin, M., Kolodner, R. and Kucherlapati, R. (1997) Mutation in the mismatch repair gene Msh6 causes cancer susceptibility. Cell 91, 467-477.
  9. Wu, G., D’Agati, V., Cai, Y., Markowitz, G., Park, J.H., Reynolds, D.M., Maeda, Y., Le, T.C., Hou, H., Jr., Kucherlapati, R., Edelmann, W. and Somlo, S. (1998) Somatic inactivation of Pkd2 results in polycystic kidney disease. Cell 93, 177-188.
  10. Cheung, V.G., Morley, M., Aguilar, F., Massimi, A., Kucherlapati, R. and Childs, G. (1999) Making and reading microarrays. Nature Genetics 21: 15-19.
  11. Edelmann, W., Cohen, P.E., Kneitz, B., Winand, N., Lia, M., Heyer, J., Kolodner, R. and Kucherlapati, R. (1999) Mammalian MutS homologue 5 is required for chromosome pairing in meiosis. Nature Genet. 21: 123-127.
  12. Wu, G., Markowitz, G.S., Li, L., D’Agati, V.D., Factor, S.M., Geng, L., Tibara, S., Tuchman, J., Cai, Y., Park, J.H., van Adelsberg, J., Hou, H., Jr., Kucherlapati, R., Edelmann, W. and Somlo, S. (2000) Cardiac and renal failure in mice with targeted mutations in Pkd2. Nature Genetics 24: 75-78.
  13. Edelmann, W., Umar, A., Yang, K., Heyer, J., Kucheralapti, M., Lia, M., Kneitz, B., Avdievich, E., Fan, K., Wong, E., Crouse, G., Kunkel, T., Lipkin, M., Kolodner, R.D. and Kucherlapati, R. (2000) The DNA mismatch repair genes Msh3 and Msh6 cooperate in intestinal tumor suppression. Cancer Research 60, 803-807.
  14. Pellegata, N.S., Dieguez-Lucena, J.L., Joensuu, T., Lau, S., Montgomery, K.T., Krahe, R., Kivela, T., Kucherlapati, R., Forsius, H. and de la Chapelle, A. (2000) Mutations in KERA, encoding keratocan, cause cornea plana. Nature Genet. 25, 91-95.
  15. Kneitz, B., Cohen, P.E., Avdievich, E., Zhu, L., Kane, M.F., Hou, Jr., H., Kolodner, R.D., Kucherlapati, R., Pollard, J.W. and Edelmann, W. (2000) MutS homolog 4 localization to meiotic chromosomes is required for chromosome pairing during meiosis in male and female mice. Genes. Dev. 14: 1085-1097.
  16. Puech, A., Saint-Jore, B., Merscher, S., Russell, R.G., Cherif, D., Sirotkin, H., Xu, H., Factor, S., Kucherlapati, R. and Skoultchi, A. (2000) Normal cardiovascular development in mice deficient for 16 genes in 550 kb of the velocardiofacial/DiGeorge syndrome region. Proc. Natl. Acad. Sci. USA 97: 10090-10095.
  17. Merscher, S., Funke, B., Epstein, J.A., Heyer, J., Puech, A., Lu, M.M., Xavier, R.J., Demay, M.B., Russell, R.G., Factor, S., Tokooya, K., St. Jore, B., Lopez, M., Pandita, R.K., Lia, M., Carrion, D., Schorle, H., Kobler, J.B., Scambler, P., Wynshaw-Boris, A., Skoultchi, A.I., Morrow, B.E. and Kucherlapati, R. (2001) TBX1 is responsible for cardiovascular defects in velo-cardio-facial/DiGeorge syndrome. Cell 104: 619-629.

 

NAME

POSITION TITLE

Roberto Guillermo Kolter, Ph.D.

Professor

EDUCATION/TRAINING

INSTITUTION AND LOCATION

DEGREE

YEAR(s)

FIELD OF STUDY

Carnegie-Mellon University, Pittsburgh, PA

B.S.

1975

Biology

University of California, San Diego, CA

Ph.D.

1979

Biology

University of California, San Diego, CA

Postdoc

1979-1980

Biology

Stanford University, Stanford, CA

Postdoc

1980-1983

Biology

Professional Experience

1983-1989 Assistant Professor of Microbiology and Molecular Genetics, Harvard Medical School

1989-1993 Associate Professor of Microbiology and Molecular Genetics, Harvard Medical School

1994- Professor of Microbiology and Molecular Genetics, Harvard Medical School

Honors and Awards

1980-1983 Helen Hay Whitney Postdoctoral Fellowship

1983-1985 Charles King Trust Fellowship

1989-1994 American Cancer Society Faculty Research Award

1992 Erskine Visiting Professorship (New Zealand)

1992-1993 Funds for Discovery Award

2000 Fellow, American Academy of Microbiology

Publications from last three years plus selected publications from prior years:

Zambrano, M.M., D.A. Siegele, M. Almirón, A. Tormo, and R. Kolter. 1993. Microbial competition: Escherichia coli mutants that take over stationary phase cultures. Science 259:1757-1760.

Siegele, D.A. and R. Kolter. 1993. Isolation and characterization of an Escherichia coli mutant defective in resuming growth after starvation. Genes & Dev. 7:2629-2640.

Yorgey, P., J. Lee, J. Kördel, E. Vivas, P. Warner, D. Jebaratnam, and R. Kolter. 1994. Novel post-translational modifications in microcin B17 define a new class of DNA gyrase inhibitor. Proc. Natl. Acad. Sci. U.S.A. 91:4519-4523.

Huisman, G. and R. Kolter. 1994. Sensing starvation: a homoserine lactone dependent signaling pathway in E. coli. Science 265:537-539.

Babbitt, P.C., G.T. Mrachko, M.S. Hasson, G.W. Huisman, R. Kolter, D. Ringe, G.A. Petsko, G.L. Kenyon, and J.A. Gerlt. 1995. A functionally diverse enzyme superfamily that abstracts the a-protons of carboxylic acids. Science 267:1159-1161.

Li, Y.M., J.C. Milne, L.L. Madison, R. Kolter, and C.T. Walsh. 1996. From peptide precursors to oxazole and thiazole-containing peptide antibiotics: microcin B17 synthase. Science 274:1188-1193.

Grant, R.A., D.J. Filman, S.E. Finkel, R. Kolter and J.M. Hogle. 1998. The crystal structure of Dps, a ferritin homolog that binds and protects DNA. Nature Str.Biol. 5:294-303.

O'Toole, G.A. and R. Kolter. 1998. Initiation of biofilm formation in Pseudomonas fluorescens WCS365 proceed via multiple, convergent signaling pathways: a genetic analysis. Molec. Microbiol. 28:449-461.

Pratt, L.A. and R. Kolter. 1998. Genetic Analysis of Escherichia coli biofilm formation: roles of flagella, motility, and type I pili. Mol. Microbiol. 285-293.

O'Toole, G.A. and R. Kolter. 1998. Flagellar and twitching motilities are necessary for Pseudomonas aeruginosa biofilm development. Mol. Microbiol. 295-304.

Finkel, S. and Kolter, R. 1999. Evolution of Microbial Diversity During Stationary Phase. Proc. Natl. Acad. Sci. (USA) 96:4023-4027.

Espinosa-Urgel, M. and Kolter, R. 1999. A novel system for efficient expression and monitoring of bacteria in aquatic environments. Env. Microbiol. 1: 175-182.

Watnick, P.I., K.J. Fullner and R. Kolter. 1999. A role for the mannose-sensitive hemagglutinin in biofilm formation by Vibrio cholerae El Tor. J. Bacteriol. 181: 3606-3609.

Wolf, S.G., D. Frenkiel, T. Arad, S.E. Finkel, R. Kolter and A. Minsky. 1999. Biocrystallization: a stress-induced strategy for wide range DNA protection. Nature 400:83-85.

Zinser, E.R. and R. Kolter. 1999. Mutations Enhancing Amino Acid Catabolism Confer a Growth Advantage in Stationary Phase. J. Bacteriol. 181:5800-5807.

Watnick, P.I. and R. Kolter. 1999. Steps in the development of a Vibrio cholerae El Tor biofilm. Mol. Microbiol. 34:586-595.

Martínez, A., S. Torello and R. Kolter. 1999. Sliding motility in Mycobacteria. J. Bacteriol. 181:7331-7338.

O'Toole, G.A., K.A. Gibbs, P.W. Hager, P.V. Phibbs and R. Kolter. 2000. The global carbon metabolism regulator Crc is a component of a signal transduction pathway required for biofilm development by Pseudomonas aeruginosa. J. Bacteriol. 182:425-431.

Goodrich-Blair H., and R. Kolter. 2000. Homocysteine thiolactone is a positive effector of ss levels in Escherichia coli. FEMS Microbiol. Lett. 185:117-121.

Newman, D.K. and R. Kolter. 2000. A role for excreted quinones in extracellular electron transfer. Nature 405:94-97.

Danese, P.N., L.A. Pratt and R. Kolter. 2000. Exopolysaccharide production is required for development of Escherichia coli K-12 biofilm architecture. J. Bacteriol. 182:3593-3596.

Recht, J., A. Martínez, S. Torello and R. Kolter. 2000. Genetic analysis of sliding motility in Mycobacterium smegmatis. J. Bacteriol. 182:4348-4351.

Zinser, E.R. and R. Kolter. 2000. Prolonged stationary-phase incubation selects for lrp mutations in Escherichia coli K-12. J. Bacteriol. 182:4361-4365.

Danese, P.N., L.A. Pratt, S.L. Dove and R. Kolter. 2000. The outer membrane protein, Antigen 43, mediates cell-to-cell interactions within Escherichia coli biofilms. Molec. Microbiol. 37:424-432.

Watnick, P.I., C.M. Lauriano, K.E. Klose, L. Croal and R. Kolter. 2001. The absence of a flagellum leads to altered colony morphology, biofilm development and virulence in Vibrio cholerae 0139. Molec. Microbiol. 39:223-235.

Frenkiel-Krispin, D., S. Levin-Zaidman, E. Shimoni, S.G. Wolf, E.J. Wachtel, T. Arad, S.E. Finkel, R. Kolter, and A. Minsky. 2001. Regulated phase transitions of bacterial chromatin: a non-enzymatic pathway for generic DNA protection. EMBO J. 20:1184-1191.

Vulic, M. and R. Kolter. 2001. Evolutionary cheating in Escherichia coli stationary phase cultures. Genetics. 158:519-26.

Recht, J. and R. Kolter. 2001. Glycopeptidolipid acetylation affects sliding motility and biofilm formation in Mycobacterium smegmatis. J. Bacteriol. 183:5718-5724.

Branda S.S., J.E. González-Pastor, S. Ben-Yehuda, R. Losick and R. Kolter. 2001. Fruiting body formation by Bacillus subtilis. Proc. Natl. Acad. Sci. (USA) 98:11621–11626.

Finkel, S.E. and R. Kolter. 2001. DNA as a nutrient: novel role for bacterial competence gene homologs. J. Bacteriol. 183:6288-6293.

Espinosa-Urgel M, R. Kolter and J.L. 2002. Root colonization by Pseudomonas putida: love at first sight. Microbiology. 148:341-343

Selected Recent Reviews:

Zambrano, M.M. and R. Kolter. 1996. GASPing for life in stationary phase. Cell 86:181-184.

Pratt, L.A. and R. Kolter. 1999. Genetic analyses of bacterial biofilm formation. Curr. Op. Microbiol. 2:598-603.

Watnick, P. and R. Kolter. 2000. Biofilm, city of microbes. J. Bact. 182:2675-2679.

O’Toole, G., H.B Kaplan and R. Kolter. 2000. Biofilm formation as microbial development. .Annu. Rev. Microbiol. 54:49–79.

Danese, P.N., L.A. Pratt and R. Kolter. 2001. Biofilm formation as a developmental process. Meth. Enzymol. 336:19-26

 

   

NAME

Martin F. Polz

POSITION TITLE

Assistant Professor

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)

FIELD OF STUDY

University of Vienna

Harvard University

Harvard University

MS

AM

Ph.D.

1991

1995

1997

Zoology

Biology

Microbiology

Professional Experience:

1997 Consultant: Ecosystems Center, Marine Biological Laboratory

1997 Postdoctoral Fellow, Harvard University

1998-present Assistant Professor, Department of Civil & Environmental Engineering, MIT

Honors and Awards:

2001 Takeda Enterpreneurship Award, Finalist

2000-2002 Doherty Professorship in Ocean Utilization

2000 Visiting Assistant Professor; Peter Wall Institute for Advanced Studies; University of British Columbia, Vancouver

1999-2001 Gilbert Winslow Career Development Chair

1994-1996 Anna Vaughn Foundation Fellowship

 

Selected Publications:

Polz, M.F., Distel, D.L., Zarda, B., Amann, R., Felbeck, H., Ott, J.A., Cavanaugh, C.M. (1994). Phylogenetic analysis of a highly specific association between ectosymbiotic, sulfur-oxidizing bacteria and a marine nematode. Appl. Environ. Microbiol. 60(12): 4461-4467.

Polz, M.F., Cavanaugh, C.M. (1995). Dominance of one bacterial phylotype at a Mid Atlantic Ridge hydrothermal vent site. Proc. Natl. Acad. Sci. USA 92: 7232-7236.

Polz, M.F., Cavanaugh, C.M. (1996). Phylogenetic relationships of the filamentous sulfur-bacterium Thiothrix ramosa based on 16S rRNA sequence analysis. Int. J. Syst. Bacteriol. 46(1): 94-96.

Polz. M. F., Cavanaugh, C.M. (1996). Ecology of ectosymbiosis at a Mid Atlantic Ridge hydrothermal vent site. in Ubilein, F., Ott, J., Stachowitsch, M. (Eds): Deep-sea and extreme shallow water habitats: affinities and adaptations. Biosystematics and Ecology Series No. 11: 337-352.

Polz, M.F., Cavanaugh, C.M. (1997). A simple method for the quantification of not-yet cultivated microorganisms in the environment based on in vitro transcription of 16S rRNA. Appl. Environ. Microbiol. 63(3): 1028-1033.

Van Dover, C.L., Polz, M.F., Robinson, J., Cavanaugh, C., Kadko, D, Hickey, J. P. (1997). Predatory anemones at TAG. BRIDGE 12: 33-34.

Tay, S.T.-L., Hemond, H.F., Polz, M.F., Cavanaugh, C.M., Krumholz, L.R. (1998). Characterization of two Toluene degrading mycobacterial isolates from a contaminated freshwater stream. Appl. Environ. Microbiol. 64(5): 1715-1720.

Polz, M.F., Cavanaugh, C.M. (1998). Bias in template-to-product ratios in multi-template PCR. Appl. Environ. Microbiol. 64(10): 3724-3730.

Polz, M.F., Robinson, J., Cavanaugh, C.M, VanDover, C.L. (1998). Trophic ecology of the massive aggregations of the hydrothermal vent shrimp Rimicaris exoculata. Limnol. Oceanogr. 43:1631-1638.

Robinson, J.J., Polz, M.F., Fiala-Medioni, A., Cavanaugh, C.M. (1998). Physiological and immunological evidence for two distinct C1-utilizing pathways in a dual endosymbiotic mussel (family Mytilidae) from the Mid-Atlantic Ridge. Mar. Biol. 132:625-633.

Tay, S.T.-L., Hemond, H.F., Polz, M.F., Cavanaugh, C.M., Krumholz, L.R. (1999). Importance of Xanthobacter autotrophicus in toluene biodegradation within a contaminated stream. Syst. Appl. Microbiol. 22: 113-118.

Polz, M.F., Harbison, C., Cavanaugh, C.M. (1999). Diversity and heterogeneity of epibiotic bacterial communities on the marine nematode Eubostricus dianae. Appl Environ. Microbiol. 65(9):4271-4275.

Polz, M.F., Ott, J.A., Bright, M., Cavanaugh, C.M. (2000) When bacteria hitch a ride. ASM News. 66(9):531-539.

Giribet, G., Distel, D. L., Polz, M. F., Sterrer, W., Wheeler, W. C. (2000). Triploblastic relationships with emphasis on the position of Gnathostomulida, Cycliophora, Plathelminthes, and Chaetognatha; a combined approach of 18S rDNA sequences and morphology. Syst. Biol. 49(3):539-562.

Tay, S.T.-L, Hemond, H.F., Cavanaugh, C.M., Krumholz, L.R., Polz, M.F. (2001). Population dynamics of toluene degrading bacterial species in a contaminated stream assessed by quantitative PCR. Microb. Ecol. 41:124-131.

Kuai, L., Nair, A., Polz, M.F. (2001). A rapid and simple MPN technique for the enumeration of dissimilatory arsenic reducing bacteria. Appl Environ. Microbiol. 67(7):3168-3173.

Lim, E., Tomita, A. Thilly, W., Polz, M.F. (2001) Combination of competitive quantitative PCR and constant dentaturant capillary electrophoresis for high resolution detection and enumeration of microbial cells. Appl. Environ. Microbiol. 67(9):3897-3903.

Oates, P.M., Shanahan, P. Polz, M.F. Solar disinfection (SODIS): simulation of solar radiation for global assessment and application for point-of-use water treatment in Haiti. Water Res. In Press.

Thompson, J., Marcelino, L., Polz, M.F. Heteroduplexes in mixed-template amplifications: formation, consequence and elimination by ‘reconditioning PCR’. Nucleic Acids Res. In Press.

 

 

 

Curriculum Vitae – Michael T. Laub

Birthdate January 5, 1976 Toronto, Canada US Citizen

Education

1997-2002 Stanford University (Palo Alto, CA)

Ph.D., Developmental Biology

Advisor: Lucy Shapiro

    1. University of California, San Diego (La Jolla, CA)

B.S., Molecular Biology

 

Research Experience

Independent Research Fellow (2002-present)

Harvard University, Bauer Center for Genomics Research

Graduate Student (1997-2002)

Stanford University, Department of Developmental Biology

Advisor: Lucy Shapiro

Thesis: "Genomic Analysis of the Genetic Network Controlling Cell Cycle Progression in Caulobacter crescentus"

Research Assistant (1996-1997)

University of California, San Diego, Department of Biology

Advisor: William F. Loomis

"Identification and characterization of a novel gene, tipC, required for Dictyostelium development" & "A differential equation model of cAMP oscillations and aggregation in Dictyostelium"

Research Assistant (1995-1997)

University of California, San Diego, Department of Biology

Advisor: Douglas W. Smith

Development of bioinformatic tools for the identification of intron-exon junctions

Fellowships, Honors

    1. Howard Hughes Predoctoral Fellowship Recipient

1997-2000 Stanford Presidential Graduate Fellowship Recipient

    1. NSF Predoctoral Fellowship Awarded

1997 Graduated Magna Cum Laude, Highest Honors in Biology, UCSD

1996 Phi Beta Kappa

1995-1997 Barry Goldwater Scholarship Recipient

 

Publications

Laub, M. T., Shapiro, L., McAdams, H. H. (2002) "Global Approaches to the Bacterial Cell as an Integrated System", in: The Bacterial Chromosome (N. Patrick Higgins, editor, ASM Press), in press.

Laub, M. T., Chen, S. L., Shapiro, L., McAdams, H. H. (2002) "Genes Directly Controlled by CtrA, a Master Regulator of the Caulobacter Cell Cycle", Proc Natl Acad Sci USA, 99, p. 4632-37.

Iranfar, N., Fuller, D., Sasik, R., Hwa, T., Laub, M. T., Loomis, W. F. (2001) "Expression patterns of cell-type-specific genes in Dictyostelium" Molecular Biology of the Cell 12, 2590-2600.

Nierman, W. C., Feldblyum, T. V., Laub, M. T., Paulsen, I. T., Nelson, K. E., Eisen, J., Heidelberg, J. F., Alley, M.R.K., Ohta, N., Maddock, J. R., Potocka, I., Nelson, W. C., Newton, A., Stephens, C., Phadke, N. D., Ely, B., Deboy, R. T., Dodson, R. J., Durkin, A. S., Gwinn, M. L., Haft, D. H., Kolonay, J. F., Smit, J., Craven, M. B., Khouri, H., Shetty, J., Berry, K., Utterback, T., Tran, K., Wolf, A., Vamathevan, J., Ermolaeva, M., White, O., Salzberg, S. L., Venter, J. C., Shapiro, L., and Fraser, C. M. (2001) "Complete genome sequence of Caulobacter crescentus strain CB15" Proc Natl Acad Sci USA, 98, p. 4136-41.

Laub, M. T., McAdams, H. H., Feldblyum, T., Fraser, C. M., Shapiro, L. (2000) "Global analysis of the genetic network controlling a bacterial cell cycle" Science 290, 2144-2148.

Judd, E. M., Laub, M. T., and McAdams, H. H. (2000) "Toggles and Oscillators: New Genetic Circuit Designs" Bioessays 22, 507-9.

Winzeler, E. A., Shoemaker, D. D., Astromoff, A., Liang, H., Anderson, K., Andre, B., Bangham, R., Benito, R., Boeke, J. D., Bussey, H., Chu, A. M., Connelly, C., Davis, K., Dietrich, F., Dow, S. W., El Bakkoury, M., Foury, F., Friend, S. H., Gentalen, E., Giaever, G., Hegemann, J. H., Jones, T., Laub, M., Liao, H., Davis, R. W., et al. (1999) "Functional Characterization of the S. cerevisiae genome by gene deletion and parallel analysis" Science 285, 901-6.

Stege, J. T., Laub, M. T., and Loomis, W. F. (1999) "tip genes act in parallel pathways of early Dictyostelium development" Develop. Genetics 25, 64-77.

Laub, M. T., and Loomis, W. F. (1998) "A molecular network that produces spontaneous oscillations in excitable cells of Dictyostelium" Molecular Biology of the Cell 9, 3521-32.

Laub, M. T., and Smith, D. W. (1998) "Finding intron/exon splice junctions using INFO, INterruption Finder and Organizer" J. Computational Biology 5, 307-21.

FACILITIES AND RESOURCES

Church Lab/ Lipper Center Facilities and Resources:

The Harvard/MIT/BU intellectual environment is excellent for multidisciplinary, collaborative and functional genomics research. The Church Laboratory provides some of the glue with students from all three universities and a location in three adjacent buildings at the heart of the HMS campus: 1) The Alpert Building is home to the Genetics department. 2) The Seeley-Mudd Building is home to the Harvard Institute of Proteomics (HIP), the Harvard Institute of Chemistry and Cell Biology (ICCB), and the Lipper Center for Computational Genetics. 3) The Thorn Building of the BW Hospital Genomics & Bioinformatics Center. Harvard has recently made considerable endowment commitments to the above and the University-wide Center for Genomics Research. We work closely with our departmental Biopolymers facility, which has a staff of five, departmental computer facility with a staff of four. We have direct computer network and CAD links to the HMS machine shop, which coordinates with several other university and commercial machining and design facilities. Other resources include:

2 Affymetrix Chip Scanners (HP & MD) and fluidics stations

1 Microarrayer prototype (Anorad stages),150 slide capacity, 16 piezoheads (GeSim)

1 microarray scanner (General Scanning 5000)

1 Automated DNA and protein sequencers, synthesizers and related items

(ABI 3700, 377, 373S, 391, 1000S, 394, 380B, 270A, 477A, 430A, 420A, 130A)

1 FPLC and Phast systems (Pharmacia)

1 LCQ HPLC-MSn Ion Trap mass spectrometer (Finnigan)

1 Storm Fluorimager with 29 exposure plates ( Molecular Dynamics)

Numerous PCR machines with 96, 384-well, and slide heads (MJR)

1 Microfluidics development platform (Caliper)

5 -20 C freezers and two -80 freezers

7 low-speed centrifuges and ultra-centrifuges (IEC, Sorvall, Beckmann)

2 Oscilloscopes and 2 electrophysiological amplifiers 70 femtoamp rms (Axon)

1 micropipette puller and microforge (Narishige)

5 high voltage (500V to 6000V) power supplies (Biorad and EC)

2 Ultra-thin gel Direct Transfer Electrophoresis (HMS shop, Cykal)

1 96-pin array oligonucleotide synthesizer Primer Station 960 (IAS & HMS)

3 electrotransfer devices (Polytech)

1 pulsed-field CHEF boxes (Genplex)

1 UV crosslinker (HMS shop)

1 Capillary array electrophoresis prototype (HMS shop)

1 Laser-induced fluorescent 4-color capillary electrophoresis (ABI 310)

2 DEC alpha fileservers running Ultrix

1 dual Intel PII, RAID level 5 based Linux fileserver

15 computers running under WinNT, 10 Linux, 6 Linux&NT, 5 MacOS

1 Silicon Graphics Octane computer

1 Linux Celeron Cluster (Beowulf-type) for parallel & associative processing

1 Terabyte tape jukebox server running Arkeia

1 Confocal Microscope (Biorad)

1 Automatic film processor

1 Bioflo 3000 mammalian and microbial cell culture chemostat (New Brunswick)

1 EPICS ALTRA flow sorter with Autoclone multiwell plates option (Beckman-Coulter)

 

Chisholm and Polz Facilities, Equipment, And Other Resources

The Polz and Chishom labs have available standard instruments required for studying and culturing bacteria and phytoplankton as well as for molecular biology, including walk-in temperature controlled incubators, highly accurate water baths, anaerobic glove box, autoclaves, fluorometers, spectrophotometer, -80 Freezer, slot blotting systems, hybridization ovens, Stratagene Eagle Eye gel quantification system for analysis of restriction fragment patterns, and a Strategene Robocycler PCR machine. We also have:

MIT also maintains a fully equipped DNA microarray facility, sequencing facilities and flow cytometry facilities, all of which are available to us. Furthermore, the Polz lab has full access to the sequencing facility maintained by the Marine Biological Laboratory (MBL).

 

CURRENT AND PENDING SUPPORT

George Church Current Research Support

DE-FG02-87ER60565 (P.I., G. Church) 12/15/99 – 11/14/02

Department of Energy-DOE

Genomic Sequence Comparisons

This project is to develop new DNA sequencing and RNA Quantitation methods

n/a (P.I., G. Church) 10/01/97 – 09/30/02

Lipper Foundation

Lipper Center for Computational Genetics

This supports general bioinformatics infrastructure and salaries

N00014-99-1-0783 (P.I., G. Church) 05/01/99 - 04/30/02

NSF and ONR

Insilico analysis of the Escherichia coli metabolic genotype and the construction of

selected isogenic strains

Our portion of this is the application of new methods to create in-frame deletions to test key

hypotheses coming from the flux-balance optimization models.

RFA HL-99-024 (P.I., Brian Seed Prime).; Sub P.I., G. Church) 09/30/01 - 09/29/05

NIH

Genomic Analysis of Stress Inflammation

Our role in this large collaboration is providing experience in microarry synthesis and

bioinformatics analysis specifically for mammalian stress response.

RFA HL-99-024 (P.I., Seigo Izumo); Sub P.I., G Church) 09/30/01 - 09/29/05

NIH

Functional Genomics of the Heart in Normal and Disease States

Our role in this large collaboration is providing experience in microarray synthesis

and bioinformatics analysis specifically for mammalian cardiovascular human studies and model systems.

 

 

n/a (P.I. G. Church.) 08/01/01 – 07/31/04

DARPA

DNA Memory I/O

 

 

 

George Church Pending Research Support

n/a (P.I.,R.Tompkins Prime); Sub PI G.Church.) 09/01/01 – 08/31/06

NIH

Inflammation and the Host Response to injury

(This has been awarded – funds are not available at this time)

n/a (P.I.,Frank McKean Prime)Sub PI G. Church)

NIH DHHS

Genomic and Proteomic Strategies for Understanding p63 Function in Epithelial Stem Cells

 

n/a (P.I. B. Palsson Prime), Sub PI G. Church) 07/01/02 - 06/30/07

NIH/BRP

Genome-scale Model of Metabolism and Regulation in Yeast

n/a (P.I. Dale Larson Prime).; Sub P.I., G. Church) 07/01/02 - 06/30/07

SPEI

Development of an unlabeled macromolecule detector

n/a (P.I., Wing Wong); Sub P.I., G Church) 04/01/02 - 03/3105

NIH

Center for Computational Study of Biological Systems

 

SALLIE W. CHISHOLM Current Support

 

DOE (MIT is subcontractor on award to U. California Berkeley/LBNL)

Establishment of Centers for Research on Carbon Sequestration in the Terrestrial Biosphere and the Oceans

$203,931

07/01/99 – 06/30/02

NSF

Regulation of Population Dynamics of Prochlorococcus and Synechococcus Ecotypes in Diverse Oceanic Ecosystems

$980,000

04/01/99 – 03/31/04

DOE

The Complete Genome Sequence of Prochlorococcus

$150,000

08/01/99 – 09/13/02

NSF

Southern Ocean Iron Experiment (SOFeX): Mesoscale Iron Fertilization Effects on Plankton Community Structure, Growth and Zooplankton Grazing

$179,020

07/15/01 – 06/30/04

NSF

SGER: Construction of a Whole Genome Micro-Array for the Marine Cyanobacterium Prochlorococcus

$96,196

03/01/01 – 02/28/03

US-Israel Binational Science Foundation

Nitrate Utilization by Prochlorococcus

$24,795

09/01/00 – 08/31/02

 

SALLIE W. CHISHOLM Pending Support

NSF

Collaborative Research: Metal-Phytoplankton Interactions Across Large Redox Gradients in the Chilean Coastal Upwelling System

$460,120

09/01/02 – 08/31/05

 

NSF

Genome Diversity and Evolution in Populations of the Marine Cyanobacterium Prochlorococcus

$1,829,108 (with 2 other Co-PIs)

09/01/02 – 09/30/05

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Current and Pending Support

Investigator:

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

Source of Support:

Total Award Amount: $

Total Award Period Covered:

Location of Project:

Person-Months Per Year Committed to the Project.

Cal:

Acad:

Sumr:

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

Source of Support: NIH

Total Award Amount: $

Total Award Period Covered:

Location of Project:

Person-Months Per Year Committed to the Project.

Cal:

Acad:

Sumr:

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

Source of Support:

Total Award Amount: $

Total Award Period Covered:

Location of Project: , Chisholm and Polz

Person-Months Per Year Committed to the Project.

Cal:

Acad:

Sumr:

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

Mechanistic determination of plutonium reduction by bacteria

 

Source of Support: DOE NABIR

Total Award Amount: $702,892

Total Award Period Covered:

Location of Project: MIT, Polz Co-PI

Person-Months Per Year Committed to the Project.

Cal:

Acad:

Sumr:

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

Source of Support:

Total Award Amount: $

Total Award Period Covered:

Location of Project:

Person-Months Per Year Committed to the Project.

Cal:

Acad:

Sumr:

*If this project has previously been funded by another agency, please list and furnish information for immediately preceding funding period.

NSF Form 1239 (10/98)

       

USE ADDITIONAL SHEETS AS NECESSARY

 

 

Current and Pending Support

Investigator: Martin Polz

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

Genome Diversity and Evolution in Populations of the Marine

Cyanobacterium Prochlorococcus

Source of Support: NSF

Total Award Amount: $1,829,108

Total Award Period Covered: 09/01/02 - 09/30/05

Location of Project: MIT (w/ 2 other co-PI's)

Person-Months Per Year Committed to the Project.

Cal:

Acad:

Sumr: 1

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

Towards environmental genomics: Can we estimate bacterial diversity in the Ocean?

 

Source of Support: NSF

Total Award Amount: $388,868

Total Award Period Covered: 08/01/02-07/31/05

Location of Project: MIT

Person-Months Per Year Committed to the Project.

Cal:

Acad:

Sumr: 0.5

Support:

Current

Pending

Submission Planned in Near Future

*Transfer of Support

Project/Proposal Title:

 

*If this project has previously been funded by another agency, please list and furnish information for immediately preceding funding period.

 

 

 

 

 

 

Additional Budget Clarifications

The Affymetrix microarray numbers and justifications:

For the Caulobacter and Pseudomonas genomes: $20K per 39,600 oligo chip

design. Then $250 per chip with a minimum of 540 chips. The per chip costs

will be spread out over the 5 years. The Pseudomonas design will be

selected to supplement the current high-density arrays for PA01 to extend

it to other ecotypes. The current resolution is 18 microns center-to-center.

Prochlorococcus: $200K per 500,000 oligo chip design and $350 per chip.

These will be made available to the community at cost. The per chip costs

will be spread out over the 5 years. These chips will be designed to

handle all three types of analyses requiring high-resolution on which we have published recently: RNAs (Selinger et al. 2000*), DNA-protein crosslinking/location (Laub et al. 2002*), and TRansposon library Array Selection Hybridization (Sassett et al. 2001; Badarinarayana 2001*)

SPECIAL INFORMATION AND SUPPLEMENTARY DOCUMENTATION

PROPRIETARY INFORMATION: None

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