We are interested in signal transduction in developmental biology.
In any intricate developmental process, the encoded genes are interpreted as myriad intercellular and intracellular interactions, all of which must occur at the right time and place. With this in mind, we are developing new methods to block or alter the activities of individual proteins in a drug-dependent manner. Our goal is to expand the repertoire of molecular tools available to developmental biologists. Rather than screen for small molecule-protein interactions we have chosen to use a directed approach to making chemically sensitive protein alleles, in which we use drug-dependent tags to regulate protein stability and localization.
The biological problem that we are interested in is the development of the neural crest and its derivatives, including the craniofacial skeleton. At present, we are developing chemical tools to study the roles of GSK-3 and Wnt signaling in the neural crest. We are using two model systems, the frog Xenopus laevis and the mouse. Xenopus embryos are abundant and live in an aquatic environment, allowing easy manipulation and drug accessibility; thus, we are using Xenopus to study early patterning and to rapidly test new tools. We then adapt these tools to mammalian systems. In the mouse, we are currently studying the development of the bony skull, using conventional and drug-dependent alleles of GSK-3β.
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