CAREER: Functional analysis of ubiquitin-mediated pathways controlling stem cell fate and tissue regeneration

点击翻译按钮获取中文摘要

Normal cellular function relies on constant regulation of protein activity and longevity. Ubiquitin ligases are enzymes that chemically couple the small polypeptide ubiquitin to other proteins to regulate their function or mark them for destruction. Ubiquitin tagging controls a wide range of key cellular processes such as cell division and cell fate decisions during development. Consequently, certain ubiquitin ligases have been implicated in many human diseases including cancer. Most animals have a large number of ubiquitin ligases (approximately 600 in humans), however, we know very little about the biological functions or specific protein targets for the majority of these enzymes. This project investigates the role of ubiquitin ligases in stem cell-based tissue regeneration using planarian flatworms as model organisms. These animals possess a large population of pluripotent stem cells that bestow upon them the remarkable ability to regenerate all of their tissues after injury or amputation. This research will identify genes encoding ubiquitin ligases in planarians and analyze their function in tissue renewal using a combination of genetic, molecular, and microscopy approaches. These experiments will reveal ubiquitin ligase genes that are required for various aspects of regeneration. The ability to inhibit ubiquitin ligase gene function in the animal will be combined with technologies designed to identify alterations in proteins modified with ubiquitin. This work will contribute to the broad goal of understanding the biological roles of ubiquitin ligases and identifying cellular targets required for stem cell regulation, tissue regeneration or body patterning.Dr. Zayas is an investigator and educator at San Diego State University (SDSU), a Hispanic Serving Institution. This project will develop a laboratory course that will integrate undergraduate students with the research outlined here. Special attention will be given to recruiting students underrepresented in science to enroll in the course. These students will be mentored on how to prepare for diverse scientific careers to support efforts to broaden participation in STEM fields. The educational activities of this proposal include science outreach at local K-12 schools to help spark enthusiasm for biology in the community.