Chris Burge, Ph.D.
Department of Biology
Associate Professor of Biology
Ph.D. Computational Biology 1997
The interests of the Burge lab revolve around the mechanisms of gene expression and regulation in higher organisms. In the course of reading out the human genome instructions, very long pre-mRNA molecules are transcribed, and then long non-coding segments (introns) are removed and the remaining segments (exons) are ligated together in the process of RNA splicing to produce the correct messenger RNA (mRNA) that will direct protein synthesis. The Burge lab integrates computational modeling and experimental methods to investigate the rules of RNA splicing that are used by the cellular splicing machinery to identify the precise locations of exons and splice sites. Their research includes studying the mechanisms of splicing regulation, developing improved algorithms to identify genes in genomic sequences, and investigating the regulation of protein expression by the recently discovered class of small non-coding RNAs known as microRNAs.
Expression of most eukaryotic genes requires removal of one or more introns. The process of intron splicing must be extremely accurate considering that a typical human transcript from one gene is over 30,000 bases long and contains 8-10 introns which must be removed with single-base precision in order to produce the correct mRNA and protein product. Inaccurate RNA splicing due to mutations in splicing signals results in altered or truncated proteins, and mutations causing aberrant splicing are involved in about 15% of all human genetic diseases. Therefore, understanding RNA splicing rules and regulation will help in predicting disease-causing mutations. RNA splicing is also frequently regulated – about half of all human genes are alternatively spliced, producing multiple distinct mRNAs and proteins from a single gene locus.
Identifying exonic splicing enhancers and silencers (ESEs and ESSs)
Post-transcriptional regulation by microRNAs
A class of genes known as microRNAs play important regulatory roles by basepairing to mRNAs to target these messages for post-transcriptional repression. We are investigating three areas of microRNA biology: (1) identifying the genes that encode microRNA molecules; (2) studying the regulation of these genes; and (3) discovering their targets. In collaboration with the Bartel lab, we have identified dozens of new microRNA genes in vertebrate and nematode genomes using a combination of computational and experimental methods, and recently we have developed an algorithm that uses RNA folding and comparative genomics to predict hundreds of conserved regulatory targets of mammalian microRNAs.
- Yeo, G. W., Van Nostrand, E., Holste, D., Poggio, T. and Burge, C. B. (2005) Identification and analysis of alternative splicing events conserved in human and mouse. Proc. Natl. Acad. Sci. USA. 102, 2850-2855.
- Wang, Z., Rolish, M., Yeo, G., Tung, V., Mawson, M. and Burge, C. B. (2004) Systematic identification and analysis of exonic splicing silencers. Cell 119, 831-845.
- Lewis, B. P., Shih, I-h., Jones-Rhoades, M. W., Bartel, D. P. and Burge, C. B. (2003) Prediction of mammalian microRNA targets. Cell 115, 787-798.
- Lim, L. P., Glasner, M., Yekta, S., Burge, C. B. and Bartel, D. P. (2003) Vertebrate microRNA genes. Science 299, 1540.
- Lim, L. P., Lau, N. C., Weinstein, E. G., Abdelhakim, A., Yekta, S., Rhoades, M. W., Burge, C. B. and Bartel, D. P. (2003) The microRNAs of Caenorhabditis elegans. Genes & Dev. 17, 977-990.
- Fairbrother, W., Yeh, R.-F., Sharp, P. A. and Burge, C. B. (2002) Predictive identification of exonic splicing enhancers in human genes. Science 297, 1007-1013.
Last Updated: April 9, 2008