个人简介

B.Sc., Biochemistry, McMaster University Ph.D., Biochemistry, University of British Columbia

研究领域

Genes in Drosophila heterochromatin, gene regulation

Our work has two long term objectives: (i) to contribute to the physical mapping/ sequencing/ functional annotation of Drosophilacentric heterochromatin, as a model for metazoan genomes, and (ii) in parallel, to study the structure, function and evolution of genes in centric heterochromatin. We have been mapping heterochromatic DNA sequences against genetic deficiencies within centric heterochromatin on chromosome 3, in order to link the genetic and physical maps in these regions. A next logical step is to use these to proceed with functional annotation—link specific genetic loci to individual gene models, by isolating DNA from individual mutants, and looking for corresponding defects in the sequence of a gene model. A key unresolved puzzle for these heterochromatic regions is the large discrepancy between the number of genetically defined loci (dozens) versus hundreds of in silico gene models. Our results to date have provided mutations in genes involved in a number of critically important cellular processes; this provides us with well-characterized heterochromatic genes, to use as substrates to study their regulation/ expression. In some cases, these mutations in essential genes provide us with a powerful tool for further studies of the structure and function of key regulatory proteins. We have also been looking at orthologues of identified D. melanogaster heterochromatic genes in the genomes of other Drosophila species . This can be a valuable tool to look for functional conservation of coding and regulatory sequences; moreover, our recent results suggest that we can make significant contributions to the annotation of these Drosophila genomes, and gain other valuable insights into the structure, function and evolution of heterochromatic genes.

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Sinclair D.A.R., M. Syrzycka, M.S. Macauley, T. Rastagardani, I. Komljenovic, D.J. Vocadlo, H.W. Brock, B.M. Honda (2009). Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Proc. Natl. Acad. Sci. 106:13427-13432. Hallson G, Syrzycka M, Beck SA, Kennison JA, Dorsett D, Page SL, Hunter SM, Keall R, Warren WD, Brock HW, Sinclair DA, Honda BM (2008). The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein. Proc Natl Acad Sci USA. 105:12405-12410. Schulze, SR, McAllister BF, Sinclair DAR, Fitzpatrick KA, Marchetti M, Pimpinelli S, Honda BM(2006). Heterochromatic genes in Drosophila: a comparative analysis of two genes. Genetics173:1433-1445. Fitzpatrick KA, Sinclair DA, Schulze SR, Syrzycka M, Honda BM (2005). A genetic and molecular profile of third chromosome centric heterochromatin in Drosophila melanogaster.Genome 48: 571-584. Schulze SR, Sinclair DA, Fitzpatrick KA, Honda BM (2005). A Genetic and Molecular Characterization of two proximal heterochromatic genes on chromosome 3 of Drosophila melanogaster. Genetics 169: 2165-2177.