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 Martha Bulyk

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Talk Title:
Transcription factor – DNA interactions: cis regulatory codes in the genome

Date/Time:
Thursday, March 17, 2011, 6:00 pm

Affiliation:
Associate Professor of Medicine and Pathology, Harvard Medical School

URL:
Martha Bulyk

Abstract:
The interactions between sequence-specific transcription factors (TFs) and their DNA binding sites are an integral part of the gene regulatory networks within cells. My group developed highly parallel in vitro microarray technology, termed protein binding microarrays (PBMs), for the characterization of the sequence specificities of DNA-protein interactions at high resolution. Using universal PBMs, we have determined the DNA binding specificities of >500 TFs from a wide range of species. These data have permitted us to identify novel TFs and their DNA binding site motifs, predict the target genes and condition-specific regulatory roles of TFs, predict tissue-specific transcriptional enhancers, investigate functional divergence of paralogous TFs within a TF family, investigate the molecular determinants of TF-DNA ‘recognition’ specificity, and distinguish direct versus indirect TF-DNA interactions in vivo. Further analyses of TFs and cis regulatory elements are likely to reveal features of cis regulatory codes important for driving appropriate gene expression patterns.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings
Compact, universal DNA microarrays to comprehensively determine transcription-factor binding site specificities.

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Introductory Speaker:
Yvonne Li, PhD Candidate, Jones Lab, Genome Sciences Centre, BCCRC

Title:
A large-scale computational approach to finding new uses for existing drugs






 Andrew Clark

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Presentation:
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Talk Title:
Human genomics with large sample size and full genome sequences

Date/Time:
Thursday, March 10, 2011, 6:00 pm

Affiliation:
Professor of Population Genetics, Department of Molecular Biology and Genetics, Cornell University

URL:
Andrew G. Clark

Abstract:
The 1000 Genomes Project has completed its pilot phases including (1) low-coverage whole-genome sequencing of 179 individuals, (2) high-coverage sequencing of two mother–father–child trios; and (3) exon-targeted sequencing of 697 individuals from seven populations. These data present an unprecedented level of detail about the allele frequency spectrum and local haplotype structure of ~15 million SNPs, 1 M indels, and 20,000 structural variants across the human genome. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes. Data from the two trios produced an estimate of 1028 germline mutations per genome per generation. These data also present an opportunity to test for past signatures of natural selection and demographic effects. In a separate study we examined sequence variation in just two genes from the ARIC cohort study of 13,715 people. This analysis resulted in nearly 4x the expected count of singleton variants which were subsequently confirmed. These data are consistent with a very recent explosive population growth model that matches the historical and archeological record. The data are also consistent with the observation that each new full human genome that is sequenced typically finds upwards of 100,000 novel SNPs that are not yet in any database.

Please note:
Trainees are invited to meet with the VanBUG speaker for open discussion
of both science and career paths. This takes place 4:30-5:30pm in either
the Boardroom or Lunchroom on the ground floor of the BCCRC

Recommended Readings:
Human genome variation
Deep resequencing

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Introductory Speaker:
Rodrigo Goya, PhD Candidate, Marra Lab, Genome Science Centre, BCCA & Meyer Lab, Centre for High-Throughput Biology (CHiBi), UBC

Title:
Characterizing alternative expression profiles in cancer samples using RNA-Seq