Understanding Appendage Regeneration in Mice

描述(申请人提供)：生物学中最大的谜团之一是某些动物如何在受到创伤时再生失去的身体部位。哺乳动物中组织再生的例子很少，而非哺乳动物物种中组织再生的研究由于缺乏分子工具而受到限制。这项研究计划旨在阐明哺乳动物组织再生是如何在基因定义的小鼠组织再生模型中展开的。目的#1将利用发育生物学、谱系追踪和条件小鼠遗传学确定组织再生的细胞基础。目的#2将确定一种特定的蛋白质在组织再生过程中调节基因表达和染色质可及性的作用。目的#2将利用定量mRNA测序(RNA-Seq)和一种新的技术来印迹染色质可及性(ATAC-Seq)。成功完成拟议的目标将极大地促进我们对哺乳动物组织再生如何展开的理解，这些知识可能会为如何触发人类组织再生并影响未来再生医学的战略提供见解。这一奖项将使首席研究员，一名皮肤科医生兼科学家，接受皮肤生物学、发育生物学和基因组学方面的强化培训，并制定独立的研究计划。此外，梁博士还将完成系统的职业发展，包括授课课程、道德操守培训和实验室管理培训。斯坦福大学正在为他提供全面的机构支持、广泛的资源以及与该领域专家合作的机会。斯坦福大学皮肤病学系在指导皮肤科医生和科学家担任独立职位方面有着良好的记录。这一奖项将帮助梁博士过渡到一个全职学术终身教职的职位，他将把90%的时间用于研究，10%的时间用于临床活动。

DESCRIPTION (provided by applicant): One of the great mysteries in biology is how do certain animals regenerate lost body parts in response to trauma. Few examples of tissue regeneration exist in mammals, and studies of tissue regeneration in non- mammalian species are limited by a lack of molecular tools. This research plan aims to elucidate how mammalian tissue regeneration unfolds in a genetically defined mouse model of tissue regeneration. Aim #1 will determine the cellular basis of tissue regeneration utilizing developmental biology, lineage tracing, and conditional mouse genetics. Aim #2 will determine the role of a specific protein in regulating gene expression and chromatin accessibility during tissue regeneration. Aim #2 will utilize quantitative mRNA sequencing (RNA-Seq) and a new technique to footprint chromatin accessibility (ATAC-Seq). Successful completion of the proposed aims will greatly advance our understanding of how mammalian tissue regeneration unfolds, and this knowledge may offer insights on how to trigger tissue regeneration in humans and impact future strategies in regenerative medicine. This award will enable the principle investigator, a dermatology trained physician-scientist, to receive intensive training in skin biology, developmental biology, and genomics, and to develop an independent research program. Additionally, Dr. Leung will complete structured career development including didactic sessions, training in ethical conduct, and training in laboratory management. Stanford University is providing him full institutional support, extensive resources, and opportunity for collaborations with experts in the field. The Stanford Department of Dermatology has a strong track record in mentoring dermatology physician-scientists to independent positions. This award will help Dr. Leung transition to a full-time academic tenure-track position where he will spend 90% of his time on research and 10% on clinical activities.