HomeResearchIntramural ResearchResearch Branches at NHGRIGenome Technology Branch Burgess Lab

Shawn Burgess, Ph.D. Investigator Genome Technology Branch Head Developmental Genomics Section B.A. Wesleyan University, 1988 Ph.D. Johns Hopkins University School of Medicine, 1995 (301) 594-8224 (301) 496-0474 burgess@mail.nih.gov Building 50, Room 5537 50 South Dr, MSC 8004 Bethesda, MD 20892-8004 Selected Publications cDNA Microarray Project

Dr. Burgess' laboratory studies developmental processes and their relation to human genetic disease. His group employs a variety of modern molecular biology methods to identify and functionally characterize novel developmental genes involved in organogenesis of the ear and maintenance of stem cell populations.

Before coming to the National Human Genome Research Iinstitute (NHGRI), Dr. Burgess was part of a group at the Massachusetts Institute of Technology that pioneered the use of pseudotyped retroviruses for mutagenesis in zebrafish. This technology represented a major breakthrough in the ability to quickly identify genes important in the early development of vertebrates. The use of retroviruses, as opposed to chemical mutagens, reduces the time for gene identification from years to weeks. The ability to expose zebrafish to these retroviruses and then quickly identify resultant mutations is allowing geneticists to perform large-scale mutagenesis and rapid phenotypic screening in a vertebrate system.

Dr. Burgess was involved in a 3-year, large-scale screening effort that used retroviral mutagenesis to produce over 525 mutations that visibly affect the development of the zebrafish embryo. Of these mutations, more than 20 affect the development of the zebrafish ear and vestibular system. His group is now studying this set of mutations to identify genes involved in the development of the vertebrate ear and establish their role in disease and normal health.

One of these genes encodes a transcription factor known as forkhead class I-1 (foxi1), which is required for ear and jaw development in zebrafish, and zebrafish foxi1 has an analog in both humans and mice. In fact, the mouse knockout model of foxi1 is deaf and has balance problems. Therefore, foxi1 is a strong candidate gene for some forms of human congenital deafness, which occurs in one per 1,000-2,000 births.

Dr. Burgess' group is using various techniques in zebrafish to define the developmental pathway in the ear and jaw that is affected by foxi1 mutations. During the first few days of development, zebrafish are relatively transparent and all their internal structures are visible. In addition, zebrafish have a robust startle response- if they do not respond to a tapping stimulus, they likely are functionally deaf. Thus, the ability to combine sophisticated embryology with high-throughput genetics makes the zebrafish an ideal animal model for studying this kind of developmental malformation.

Dr. Burgess continues to expand the functionality of the pseudotyped retroviruses for use in new large-scale screens for gene function. The next challenge his laboratory faces is devising screens that are not based solely on knocking out genes; these new approaches will allow for conditional expression, misexpression, or rapid tissue expression screening. For example, his group recently helped produce a transgenic zebrafish from cultured sperm infected with a pseudotyped retrovirus in vitro. The collected sperm was used to perform the in vitro fertilizations, and transgenic embryos were identified.

The transgenic fish transmitted the proviral integration to the next generation in a Mendelian fashion. This approach for generating transgenic animals opens the door for the rapid generation of transgenic lines in model organisms that are otherwise intractable to transgenesis.

Another aspect of development being studied by Dr. Burgess' group involves stem cell biology. His group has isolated a mutant stem cell gene in zebrafish that is a homolog of a gene in mice called Oct4. In mice, the Oct4 gene product maintains stem cell pluripotency by activating and repressing multiple downstream genes. Although the precise mechanism by which the Oct4 protein represses downstream genes remains unknown, when it is removed from stem cells, they begin to differentiate. Dr. Burgess' group has developed an Oct4-deficient zebrafish and is conducting trans-species transcriptional profiling in both zebrafish and mice to compare the genetic profiles of the two species.

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Last Updated: August 1, 2008