Dr. Robert Holt

Titles and Education

Titles

Head of Sequencing, Genome Sciences Centre, BC Cancer Agency
Associate Professor, Department of Molecular Biology and Biochemistry, Simon Fraser University
Associate Professor, Department of Psychiatry, University of British Columbia

Education

B.Sc.  - Biology, University of British Columbia, 1992
Ph.D.  - Pharmacology, University of Alberta, 1998

Applications are welcome from prospective Post-Doctoral Fellows

Research

Immunology

T cell receptors (TCRs) present on T lymphocytes recognize antigenic peptides presented at the cell surface by MHC. In T lymphocytes, during thymic development, TCR loci undergo somatic VDJ recombination to generate a diverse metagenome in every individual. The complexity and dynamics of the T cell repertoire remain unknown because the potential size of the repertoire (>10¹² possible clonotypes) has made conventional sequence analysis cost prohibitive. We are using the next generation sequencing and a novel short reach assembly strategy to explore the human T cell repertoire in human peripheral blood. Characterizing diversity of the T cell repertoire has important applications in vaccine development for cancer and infectious disease.

Neurobiology

The genetics of complex psychiatric disease. The causes of disorders such as schizophrenia and bipolar disorder remain unknown. We are using DNA sequence analysis, microsattelite analysis, genomic microarrays, and IP/MS to explore candidate genes for these and other disorders

Gene therapy for brain disorders.  As an investigator on the Pleiades Promoter Project (www.pleiades.org) we are developing synthetic human promoter systems suitable for driving gene expression in specific brain regions of therapeutic interest.

Synthetic Biology

There has been spectacular success reading genetic code. In contrast, progress made in writing genetic code and building genomes has been extremely limited. The new field of synthetic biology explores these possibilities. Our current work in synthetic biology focusses on developing laboratory methods for constructing large DNA molecules, engineering whole microbial genomes and exploring microbial genome interaction.

Evolutionary Biology

Gene duplication is the primary mechanism for generating evolutionary novelty.  We are exploring gene duplication in primates and other model systems, with a particular focus on brain evolution.

DNA sequencing

The Sequencing Group at BCGSC provides an efficient, flexible, reliable high throughput platform to support collaborative research related to human disease, model organisms, and organisms of industrial importance in Canada. Technology development is ongoing.

Select Publications

Mead C-LR, Kuzyk MA, Moradian A, Wilson GM, Holt RA and Morin GB. Cytosolic Protein Interactions of the Schizophrenia Susceptibility Gene Dysbindin. J. Neurochemistry. 2010 Mar 17. [Epub ahead of print]

Warren RL and Holt RA. A census of predicted tumour mutational epitopes. Human Immunology. 2010, 71(3):245-54. [Epub ahead of print Jan 9]

Romanuik TL, Wang G, Holt RA, Jones SJM, Marra MA, Sadar M. Identification of novel androgen-responsive genes by sequencing of LongSAGE Libraries. BMC Genomics 2009, 10:476

Shah SP, Morin R, Khattra J, Prentice L, Pugh T, Burleigh A, Delaney A, Gelmon K, Guliany R, Senz J, Steidl C, Holt RA, Jones S, Sun M, Leung G, Moore R, Severson T, Taylor G, Teschendorff AE, Tse K, Turashvili G, Varhol R, Warren RL, Watson P, Zhao Y, Caldas C, Huntsman D, Hirst M, Marra MA, Aparicio S. Mutational evolution and RNA editing in a lobular breast tumour profiled at single nucleotide resolution. Nature. 2009, 461:809-813

The MGC Project Team. The Completion of the Mammalian Gene Collection (MGC) Genome Research. Genome Res. 2009 Oct 28. [Epub ahead of print]. Abstract

Pel J, Broemeling D, Mai L, Poon H-L, Tropini G, Warren RL, Holt RA, Marziali A. Non-linear Electrophoretic Response Yields a New Parameter for Separation of Biomolecules. PNAS 2009. 106(35):14796-801. Epub 2009 Aug 17..

Freeman JD, Warren RL, Webb JR, Nelson BH and Holt RA. Profiling the T-cell Receptor Beta-chain Repertoire by Massively Parallel Sequencing. Genome Research 2009, 19:1817-1824. Abstract

Wang X et al, Identification of genes expressed in the hermaphrodite germ line of C. elegans using SAGE. BMC Genomics 2009, 10:213

The Bovine Sequencing and Analysis Consortium. The Genome sequence of taurine cattle: A window to ruminant biology and evolution. Science. 2009 April 24 324(5926): 425-556.

Meissner B, Warner A, Wong K, Dube N, Lorch A, McKay SJ, Khattra J, Rogalski T, Somasiri A, Chaughry I, Fox RM, Miller III DM, Baillie DL, Holt RA, Jones SJM, Marra MA, Moerman DG. An integrated strategy to study muscle development and myofilament structure in Caenorhabditis elegans. PLoS Genetic. 2009. 5(6): e1000537.

Warren RL, Nelson BH, Holt RA. Profiling model T cell metagenomes with short reads. Bioinformatics. 2009 Feb 15;25(4):458-464. Abstract

Yang GS, Banks KG, Bonaguro RJ, Wilson G, Dreolini L, de Leeuw CN, Liu L, Swanson DJ, Goldowitz D, Holt RA, Simpson EM. Next generation tools for high-throughput promoter and expression analysis employing single-copy knock-ins at the Hprt1 locus. Genomics. 2009. 93(3):196-204. Epub 2008 Dec 3.Abstract

D'Souza CA, Chopra V, Varhol R, Xie YY, Bohacec S, Zhao Y, Lee LL, Bilenky M, Portales-Casamar E, He A, Wasserman WW, Goldowitz D, Marra MA, Holt RA, Simpson EM, Jones SJ. Identification of a set of genes showing regionally enriched expression in the mouse brain. BMC Neurosci. 2008. 14:9:66.

Robert Holt's Complete Publications List including selected links to full text articles.