Norbert Perrimon, Ph.D.
|Title||James Stillman Professor of Developmental Biology|
|Institution||Harvard Medical School|
|Address||Harvard Medical School|
Genetics NRB Room 336G
77 Avenue Louis Pasteur
Boston MA 02115
Available: 09/01/12, Expires: 09/27/13
Research in Norbert Perrimon laboratory
Genetic dissection of pathways involved in stem cell biology
We have recently identified novel stem cell populations residing in the Drosophila gastrointestinal tract that provide a unique system to apply the powerful genetic tools available in this organism to identify new factors and pathways that regulate the number of stem cells and their differentiation [Micchelli, C. and Perrimon, N. (2006) Evidence that stem cells reside in the adult Drosophila midgut epithelium. Nature. 439, 475-479]. The Drosophila gut is an ideal system to study stem cell biology because, while it is simpler than that in mammals, it is highly similar at cellular and molecular levels. For example, both systems rely on multipotent stem cells to replenish the loss of two broad classes of cell types—absorptive and secretory cells—that regularly undergo apoptosis and delamination into the gut lumen. Moreover, the molecular basis driving the differentiation of stem cell daughters into either absorptive or secretory cells appears to be conserved, such that in both mammals and Drosophila, high levels of signaling by the Notch pathway promotes differentiation to the absorptive cell fate by inhibiting development of the secretory fate (which requires only low levels of Notch signaling). Thus, the overall biology of Drosophila gut stem cells appears to recapitulate the major features of mammalian gut stem cell biology. We have recently developed a powerful luciferase-based assay that enables us to efficiently carry out screens for genes and bioactive chemicals that affect stem cell growth in the adult Drosophila gut. The student will participate in our ongoing project to develop models of human stem cell colon cancer using the Drosophila gut as a model system and will apply our luciferase technology to carry out pilot screens for genes and small molecules that can have therapeutic effects.
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