The development of animals ranging from flat worms and fruit flies to humans relies on communications between cells mediated by Hedgehog (Hh) family of signal proteins. The primary cilia, tiny 'hairs' on the surface of most of our cells, are needed for cells to respond to Hh, but it remains unclear how they achieve this important function. This project focuses on Gli2, which turns on gene expression in response to Hh. First, the PI will take a molecular approach to test the hypothesis that the transportation of Gli2 into the cilia share the same mechanism used for its transportation into the nucleus. Subsequently, the PI will perform a structure/function analysis to define amino acids in Gli2 protein critical for its ciliary localization. Finally, the PI will create a genetically engineered mouse that produces a Gli2 protein incapable of entering the cilia. Using this mouse, the PI will test the hypothesis that Gli2 activity is turned on specifically in the cilia. Recent reports linked the cilia to many other signal proteins (e.g. Wnt, Bmp, PDGF etc); hence this research will not only advance understanding of how Hh regulates cell behavior through cilia-based signaling, but also provide more general insight into how cilia regulate information flow to ensure normal development of an animal.
The integration of research and education will be achieved by applying the research material to undergraduate teaching, encouraging undergraduate students to participate in lab research and providing opportunities for graduate students to be involved in teaching activities. Female and minority students will be recruited to participate in this project through NASA-sponsored programs. Finally, the PI will be actively involved in outreach activities such as participating in Pennsylvania Junior Academy of Science activities (K-12 education) and Upward-bound programs for first-generation, economically-challenged students.
