The completion of the Human Genome Project gave us an unprecedented view of the organization of a vertebrate genome, but it also raised as many questions as it answered. One key discovery was that it took approximately 20,000 genes to make a human being. However, for more than 14,000 of those genes, the function has never been tested in any organism. This becomes a significant problem when researchers are attempting to show a link between a specific gene and a biological trait or a human disease.
For more than a decade, the focus of the Developmental Genomics Section has been to develop techniques for high-throughput testing of gene function in vivo, using zebrafish as a vertebrate model system. Much of the lab effort revolves around systematically inactivating genes by mutation to see the resulting effect on the animal (i.e. the phenotype). Initially, this involved causing random lesions in the genome and identifying when the lesions inactivated genes. These mutant fish were cryopreserved to create a library of gene knockouts in zebrafish. Newer technologies have enabled a shift effort towards directed gene knockouts using genomic editing via targeted nucleases.
The Burgess group has subsequently developed a pipeline for large-scale, targeted knockout of zebrafish genes. They are applying this knockout pipeline to a variety of questions important to understanding aspects of both fundamental biological processes and to the causes of rare human genetic diseases. In collaboration with clinical researchers, the group is systematically making zebrafish models for human neurological disorders, deafness, inflammatory diseases and other rare genetic abnormalities. They are also systematically disrupting cell-signaling pathways such as the receptor tyrosine kinases or hypoxia related responses to understand these fundamental processes. The ultimate goal of the Developmental Genomics Section is to identify an in vivo function for every gene in the vertebrate genome.
Dr. Burgess received his Ph.D. in genetics from the Johns Hopkins University School of Medicine, where he studied the genetics of mitochondrial fusion and fission in yeast. He trained with Nancy Hopkins, Ph.D., at the Massachusetts Institute of Technology, where he was part of a large effort to develop insertional mutagenesis in zebrafish, coupled with a genetic screen to identify genes essential for early development of a vertebrate. Since 2001, he has been at the National Human Genome Research Institute, where he is a senior investigator and heads the Developmental Genomics Section.
Much of Dr. Burgess' work in the last decade has been focused on developing efficient gene knockout technologies in zebrafish, coupled with efficient phenotyping of the gene disruptions.
Top of page
Last Updated: January 5 , 2015