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Robert W. Blakesley, Ph.D. Associate Investigator Genome Technology Branch Director Sequencing Group NIH Intramural Sequencing Center A.B. University of California, Berkeley, 1969 Ph.D. Michigan State University, 1974 (301) 435-6157 (301) 435-6170 rblakesl@mail.nih.gov 5625 Fishers Ln Room 5N-01C, MSC 9400 Rockville, MD 20892-9400 Selected Publications NIH Intramural Sequencing Center

Dr. Blakesley directs the Sequencing Group of the NIH Intramural Sequencing Center (NISC). Established in 1997, NISC is a multidisciplinary genomics facility that emphasizes the generation and analysis of DNA sequences. Dr. Blakesley has had a career-long scientific interest in providing practical technological solutions to research problems. He spent more than 20 years in an industrial molecular biology research and development laboratory, developing products in a number of areas, including nucleic acid enzymology, purification and manipulation of nucleic acids, apparatus and software design, and DNA sequencing. His work focuses on improving NISC's sequencing pipeline by developing more consistent large-scale DNA purification methods, using robotics to increase overall efficiency and to reduce costs, as well as applying good manufacturing principles.

Dr. Blakesley oversees NISC's role in several large DNA sequencing efforts. The NISC Comparative Sequencing Program has two components: inter-species sequence comparisons, which includes providing most of the sequence data for the ENCODE Project, and intra-species sequence comparisons, which involves re-sequencing human DNA within the context of medical-sequencing projects.

The first component is an exciting effort to generate and analyze sequence from targeted genomic regions in a wide variety of vertebrates for comparative analyses. Sequencing is performed using a fairly conventional BAC-based shotgun strategy, where selected BACs are subcloned and the resulting plasmid subclones sequenced from both ends. Resulting data are being used to develop and refine computational tools for comparing genomic sequences from different vertebrates. Included in this effort is NISC-generated sequence for the ENCODE Project, an NHGRI-led initiative that aims to identify all the functional elements in the human genome. Its initial effort is a pilot-scale program that is focusing on 1 percent of the human genome, distributed across 44 discrete regions. In partnership with other NHGRI investigators, NISC is extensively involved in generating these multi-species sequences and analyzing the resulting data.

For the intra-species comparative-sequencing component, we recently developed and implemented protocols for generating and sequencing PCR-amplification products derived from human genomic DNA. A key factor in the implementation of this capability has been the seamless integration into and use of the bulk of our established sequencing pipeline, thereby maximizing efficiencies and economies-of-scale. A developing program that will utilize the majority of this sequencing capacity is the ClinSeq project, where we hope to learn how to do genome sequencing in a clinical research setting.

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Last Updated: August 1, 2008