計畫摘要

Keywords and Abstracts (Chinese and English)
Key Words: liver, genomics, epigenomics, sn-expression, liver cancer

The research program proposed in the proposal is an extension of the Program for Promoting Academic Excellence in Universities (PPAE) supported by Ministry of Education. The overall goal of PPAE project has been to set up a modern genome research program in Taiwan. Because the nature of genome research requires very different approach than the traditional research program we decided that three components are essential for the success of such an endeavor: 1) Set up modern core facilities and technologies of genome research, 2) Form a collaborating research team with focus of a research program, and 3) Train the students and research personnel in the modern knowledge of genome research. Under the support of this grant, we have set up 10 modern core facilities in genome research, two of them have since become independent. We also formed a tightly working group focusing on gene expression program of mouse liver regeneration. Four graduate education programs have been set up: developmental biology, structural biology, bioinformatics and genetic counseling with participation from the faculties of Academia Sinica.? Because this is a fast moving field, we have been up-dating the facilities and technologies as well as the research program. Two years ago we decided that the new and emerging epigenomic approach and syn-regulatory pathway control are very important for the future of genome research and have since then begun exploring this area by developing our own techniques and the ways to link between genomic and epigenomic approaches. Thus the overall goal of this program project is to utilize the genomic as well as the epigenomic tools to deduce the syn-expression pathways in organ-level using liver regeneration and development as a model with the long-term objective of applying the knowledge obtained for understanding the genetic basis underlying the mechanism of organogenesis and disease processes in this organ. We chose liver as the target organ for investigation of syn-regulated gene expression program based on the following considerations: 1) this is the main research program active in the Yang-Ming-VGH campus, 2) liver cancer and hepatitis are major health problems in Taiwan, 3) liver’s unique regeneration capacity and tissue organization are useful for dissecting genetic controls involved in the orchestration of gene expression at organ level.? We approach this goal by global analysis from genomic (component 1) and epigenomic (component 2) aspects, coupled with powerful genetic and reverse-genetic approaches of model organisms for addressing phenotypes and biological functions (components 3-5) and finally an application arm to apply the knowledge and technologies obtained to human liver diseases (component 6). The results of these approaches will be constantly cross-examined through active discussions and new experiments designed based on the new information developed.