Abstract

We propose here the Molecular and Genomic Imaging Center (MGIC) in response to a biomedical-community-wide need for flexible, cost-effective, high-resolution technology to identify and characterize variation in biological systems at the level of genomes and transcriptomes. We plan to help meet this need by developing the polymerase colony, or polony, technology. Polonies represent a highly parallel method of nucleic acid analysis that is realistic, close-at-hand, modular, and versatile. The primary mission of the MGIC is to efficiently integrate a diverse set of contributions from technology developers into a robust platform that can be smoothly disseminated to a variety of users with specialized clinical and biological interests. These are the main aims: (1) Highly parallel fluorescent in situ sequencing. (2) Single molecule profiling of the transcriptome, in particular of neural differentiation and of mammalian alternative splicing. (3) Direct molecular haplotyping and long-range sequence connectivity. (4) Characterization of DNA & RNA from single cells, in particular characterizing asymmetric cell division in mammalian stem cells. (5) Computational algorithms and systems modeling addressing combinatorial and spatial patterns in nucleic acid analysis. (6) An ELSI component focuses on issues of translation of technology to clinical applications and challenges to the concepts of anonymity. ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Specialized Center (P50)
Project #
5P50HG003170-05
Application #
7485147
Study Section
Ethical, Legal, Social Implications Review Committee (GNOM)
Program Officer
Schloss, Jeffery
Project Start
2004-07-01
Project End
2010-04-30
Budget Start
2008-05-01
Budget End
2010-04-30
Support Year
5
Fiscal Year
2008
Total Cost
$2,016,675
Indirect Cost

  Institution

Name
Harvard University
Department
Genetics
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Huh, Yang Hoon; Noh, Minsoo; Burden, Frank R et al. (2015) Sparse feature selection identifies H2A.Z as a novel, pattern-specific biomarker for asymmetrically self-renewing distributed stem cells. Stem Cell Res 14:144-54
Krier, Joel B; Green, Robert C (2015) Management of Incidental Findings in Clinical Genomic Sequencing. Curr Protoc Hum Genet 87:9.23.1-16
Wang, Catharine; Gordon, Erynn S; Stack, Catharine B et al. (2014) A randomized trial of the clinical utility of genetic testing for obesity: design and implementation considerations. Clin Trials 11:102-13
Krier, Joel B; Green, Robert C (2013) Management of incidental findings in clinical genomic sequencing. Curr Protoc Hum Genet Chapter 9:Unit9.23
Green, Robert C; Berg, Jonathan S; Grody, Wayne W et al. (2013) ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med 15:565-74
Wang, Haoyi; Mayhew, David; Chen, Xuhua et al. (2012) ""Calling cards"" for DNA-binding proteins in mammalian cells. Genetics 190:941-9
Eroshenko, Nikolai; Kosuri, Sriram; Marblestone, Adam H et al. (2012) Gene Assembly from Chip-Synthesized Oligonucleotides. Curr Protoc Chem Biol 2012:
Noh, Minsoo; Smith, Janet L; Huh, Yang Hoon et al. (2011) A resource for discovering specific and universal biomarkers for distributed stem cells. PLoS One 6:e22077
Wang, Haoyi; Mayhew, David; Chen, Xuhua et al. (2011) Calling Cards enable multiplexed identification of the genomic targets of DNA-binding proteins. Genome Res 21:748-55
Zhang, Feng; Cong, Le; Lodato, Simona et al. (2011) Efficient construction of sequence-specific TAL effectors for modulating mammalian transcription. Nat Biotechnol 29:149-53

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