Dr. Robert Holt, Professor B.Sc., Biology, University of British Columbia Ph.D., Pharmacology, University of Alberta Phone: 604-675-8165 Email: rholt@bcgsc.ca Research website Lab website

Research Interest

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.

• Publications