 |
Jack Chen, Associate ProfessorDepartment of Molecular Biology and Biochemistry
Office: SSB8111 |
RESEARCH INTERESTSMy laboratory is interested in developing novel bioinformatics and genomics data mining programs and in applying these programs in identifying novel genes, structural variations, and regulatory mechanisms. The ultimate goal is to understand, using combined computational and experimental approaches, gene structure, function, and regulation in health and disease conditions. We use the nematode Caenorhabditis elegans as a model system. However, bioinformatics programs developed are readily applicable in organisms ranging from bacteria to humans. Research projects in my laboratory follow several intertwining directions: gene finding and gene family characterization, genome structural variations and molecular evolution, transcriptional regulation of development and physiology, brain genomics, and transcriptional regulation of host-pathogen interactions. |
|
Gene discovery and gene family identification Although many gene finding programs have been developed, accumulating evidence indicates that a large number of genes remain to be discovered. It has been shown that gene finding using computer algorithms alone is not adequate. We are developing a set of combined computational and experimental approaches to identify novel genes in the Caenorhabditis genomes. In the meantime, we are also developing programs to identify gene families. A gene family consists of a group of genes that share structural and functional features. For example, the C. elegans genome carries >1,000 chemosensory genes, which can be divided into many gene families, including the srab gene family we have identified (Chen et al., 2005). |
|
Genome structural variations and molecular evolution Genes are not randomly distributed in a genome. On the one hand, the arrangement of genes and functional elements has been shown to critical in gene expression regulation. In C. elegans, for example, we have demonstrated that divergent and parallel neighboring gene pairs are positively correlated in gene expression, while convergent neighboring gene pairs either lack such correlation or show some negative correlation (Chen and Stein, 2006). On the other hand, a genome is a highly dynamic structure. Each genome contains significant number of structural variations including structural rearrangements via insertions, deletions, tandem repeats, inversions, and single nucleotide polymorphisms (SNPs). Many genomic rearrangements have been associated with well-defined clinical syndromes. |
|
Transcriptional regulation in health and disease Transcriptional regulation controls unique combinations of genes expressed in cells, which in turn determines cell identity and function. Approximately 5% of the protein coding capacity of any genome encodes transcription factors (TFs), which present an enormous regulatory capability at the transcription level alone. Each TF regulates up to hundreds of genes by binding to their promoters/enhancers, while each gene can be transcriptionally regulated by an array of TFs. Such many-to-many transcriptional relationships create a large number of transcriptional regulatory circuits (TRCs) and eventually many elaborate transcriptional regulatory networks (TRNs). Identification and understanding of transcription factor binding sites (TFBSs) holds the key to understanding TRCs and TRNs. By applying comparative genomics, microarray analysis, SAGE (serial analysis of gene expression), we have identified a large number of target genes of DAF-19, a tissue-specific transcription factor, in C. elegans. Notably, many of these target genes are C. elegans orthologs of human Bardet-Biedl Syndrome (BBS) genes (Chen et al, 2006). This project is currently supported by NSERC and the SFU President's Research Grants Fund. |
|
Brain genomics After the completion of the human genome project, one of the most interesting but challenging projects is the study how the brain works, both in physiological (learning and memory, etc.) and in pathological conditions (Parkinson's Disease, Huntington's Disease, etc). We are especially interested in discovering and exploring genes, pathways, and biological networks in the nervous system using comparative and functional genomics approaches. In particular, we are interested in identifying and investigating novel genes that function in sensory perception, synaptic signal transduction, and neurondegenerative conditions. |
|
Transcriptional regulation of host-pathogen interaction The relationships between host and pathogens are antagonisc interactions. The outcome of such interactions depends on the virulence of the pathogen and on the susceptibility and resistance of the host. We are interested in characterizing genes, in host and pathogens, and their transcriptional regulation. This project is currently supported by the SFU Community Trust Endowment Fund (CTEF). |