ABSTRACT Our overall goal is to strengthen our Developmental Biology COBRE by mentoring five newly-recruited investigators, each studying important questions in Developmental Biology with translational implications. We will build upon our success in Phase I when our COBRE Investigators made important discoveries resulting in 53 published papers (many in high-impact journals), 91 presentations at invited seminars or scientific meetings, and the awarding of more than $9.75 million in external funding, including 3 R01s and a R56. We will also continue to build our infrastructure by strengthening and expanding our scientific Cores. Developmental Biology is fundamental to progress in determining the molecular basis of many diseases, as well as for the rapidly emerging field of regenerative medicine. Our new Junior Investigators will use a variety of experimental model systems to explore fundamental developmental processes that are compromised by disease, or might be manipulated to promote healing. Their research areas include intestinal regeneration (planarians), stress responses and aging (C. elegans), mucous cell hyperplasia leading to chronic obstructive pulmonary disease (human cell culture and mouse models), genetics of deafness (zebrafish), and neurodegenerative diseases (Drosophila). The addition of five new Junior Investigators will help create the critical mass necessary for a sustainable community where Developmental Biologists can flourish. Phase II COBRE support will allow us to implement an ideal program for launching the careers of these new investigators by providing committed mentoring from internal and external scientists, building and maintaining outstanding Core facilities for advancing Developmental Biology research, and integrating the new investigators into the growing Developmental Biology community in Oklahoma. This will be accomplished through the following Specific Aims: Aim 1. To grow our multi-disciplinary research program in Developmental Biology through the nurturing of a talented group of Junior Investigators with outstanding potential to become leaders in their fields Aim 2. To mentor the Junior Investigators, using a combination of senior scientists and recently graduated COBRE Junior Investigators within existing OMRF and University of Oklahoma faculty Aim 3. To form an External Advisory Committee of internationally recognized Developmental Biologists to evaluate the progress of, and offer advice to, the Junior Investigators Aim 4. To maintain and expand Core facilities that will support the research of the Junior Investigators and lay the groundwork for their sustainable operation after COBRE funding ends. Aim 5. To promote scientific interactions among the Junior Investigators and create an environment conducive to investigator retention.

Narrative The five highly talented Junior Investigators in this Phase II COBRE will use model organisms to study fundamental issues in Developmental Biology with direct relevance to human health. These include mechanisms of intestinal regeneration (planarians), cell fate decisions in the development of chronic obstructive pulmonary disease (mice), genetics of deafness (zebrafish), transcriptional control of longevity (C. elegans), and mitochondrial dynamics in neurodegenerative diseases (Drosophila).