Barry M. Honda

Professor Emeritus
Molecular Biology & Biochemistry
Science

Areas of interest

Our work has had two long term objectives:

(i) to contribute to the physical mapping/ sequencing/ functional annotation of Drosophila centric heterochromatin, as a model for metazoan genomes, and
(ii) in parallel, to study the structure, function and evolution of genes in centric heterochromatin.

Heterochromatin is defined as the darkly-staining, densely-compacted part of chromosomes, generally found near centromeres and telomeres. One defining characteristic of heterochromatin is its high levels of repeated DNA sequences, which make genome sequencing and molecular analysis very challenging. In Drosophila, a large proportion of the genome (up to 1/3) is found packaged in heterochromatin, and it has been extremely difficult to study genes in these regions, because most standard fly genetic and molecular tools are not available.

We have been working on a genetic map to identify essential genes in the centric heterochromatin of Drosophila chromosome 3. The task requires special genetic methods--generating and characterizing large deletions (Deficiencies/Dfs) of DNA within heterochromatin—followed by use of these Dfs to isolate mutations, which allow us to study previously uncharacterized genes. The work serves to link the genetic and physical maps of chromosome 3 heterochromatin, as well as generating powerful genetic and molecular tools to study genes in these poorly understood regions of the genome. This work has been complemented by studying the same genes in other Drosophila species, to identify important features conserved during evolution.

Our results to date have made contributions to genomics and the functional annotation of heterochromatic DNA sequences. The work has also provided new insights into the expression and regulation of a number of interesting heterochromatic genes, many of which are involved in critically important cellular processes.

Education

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

Selected Publications

  • Genetic and Molecular Analysis of Essential Genes in Centromeric Heterochromatin of the Left Arm of Chromosome 3 in Drosophila melanogaster. Hallson G, Syrzycka M, Fitzpatrick KA, Kim I, Cotsworth SEP, Hollebakken RE, Simonetto K, Yang L, Luongo S, Beja K, Coulthard AB, Hilliker AJ, Sinclair DA and BM Honda. Manuscript in preparation
  • The heterochromatic Gfat1/zep (Glutamine:Fructose-6-Phosphate Aminotransferase 1/zeppelin) gene, and its euchromatic paralogue Gfat2, encode functionally equivalent enzymes in the hexosamine biosynthesis pathway (HBP) in Drosophila. Cotsworth SEP, Jackson CJ, Hallson G, Fitzpatrick KA, Syrzycka M, Bejsovec A, Hilliker AJ, Marchetti M, Pimpinelli S, Sinclair DAR and BM Honda. Manuscript in preparation
  • Cooperative Control of Ecdysone Biosynthesis in Drosophila by Transcription Factors Séance, Ouija board, and Molting Defective. Uryu O, Ou Q, Komura-Kawa T, Kamiyama T, Iga M, Syrzycka M, Hirota K, Kataoka H, Honda BM, King-Jones K, Niwa R. (2018) Genetics 208: 605–622.
  • Genome-wide chemical mapping of O-GlcNAcylated proteins in Drosophila melanogaster. Liu TW, Myschyshyn M, Sinclair DA, Cecioni S, Beja K, Honda BM, Morin RD, Vocadlo DJ. (2017) Nat Chem Biol. 13:161-167
  • dSet1 is the main H3K4 di- and tri-methyl-transferase throughout Drosophila development. Hallson G, Hollebakken RE, Li T, Syrzycka M, Kim I, Cotsworth S, Fitzpatrick KA, Sinclair DAR and BM Honda (2012) Genetics 190: 91-100.
  • Drosophila O-GlcNAc transferase (OGT) is encoded by the Polycomb group (PcG) gene, super sex combs (sxc). Sinclair D.A.R., M. Syrzycka, M.S. Macauley, T. Rastagardani, I. Komljenovic, D.J. Vocadlo, H.W. Brock, B.M. Honda*. (2009) Proc. Natl. Acad. Sci. 106:13427-13432.
  • Collapse of germline piRNAs in the absence of Argonaute3 reveals somatic piRNAs in flies. Li C, Vagin VV, Lee S, Xu J, Ma S, Xi H, Seitz H, Horwich MD, Syrzycka M, Honda BM, Kittler EL, Zapp ML, Klattenhoff C, Schulz N, Theurkauf WE, Weng Z, Zamore PD*. (2009) Cell 137:509-521.
  • The Drosophila cohesin subunit Rad21 is a trithorax group (trxG) protein. Hallson G, Syrzycka M, Beck SA, Kennison JA, Dorsett D, Keall R, Page SL, Warren WD, Brock HW, Sinclair DAR and BM Honda (2008) Proc. Natl Acad Sci 105:12405-12410.
  • 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 USA105:12405-12410. 
  • 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.