PostDoctoral Research Fellowship in Biological Informatics FY2006

项目名称：鹿鼠（Peromyscus属）在高海拔和低氧条件下携氧血液蛋白的进化。本课题为2006年度生物信息学博士后科研资助项目。深入了解使生物体能够在极端条件下发挥作用的遗传结构，可以大大增加我们对负责自然变异起源和维持的进化过程的理解。本研究的目的是阐明鹿小鼠（Peromyscus sp.）对高海拔缺氧条件的生理适应的分子基础。这项跨学科的研究将涉及对编码血红蛋白α -和β -球蛋白亚基的基因中自然发生的变异的分子遗传学、生物物理学和生化分析。将对α -和β -珠蛋白链的DNA变异进行分析，以确定选择对固定血红蛋白变异的作用，并量化蛋白质-蛋白质相互作用如何影响该分子的遗传结构。利用蛋白质模型，计算机分析将预测血红蛋白分子在不同氧气条件下的功能。将进行生化分析来检验这些预测。通过结合DNA序列变异的进化分析和蛋白质的计算机和体外分析，本研究将提供血红蛋白结构和功能的全面分析。这些数据将为不同氧气条件下蛋白质变异如何影响整个生物体的呼吸生理提供可测试的预测。该博士后将在内布拉斯加大学林肯分校的Jay Storz实验室工作，在那里她将接受分子生物物理学、生物化学和结构生物学的理论和方法培训。通过将这些技能与该研究员在分子进化、系统发育和群体遗传学方面的专业知识相结合，这一经历将使她能够发展自己的研究计划，专注于综合生物学。除了研究经验外，该研究员还将为生物学学生开设一门课程，向他们介绍蛋白质生物物理分析的理论和方法。

Project Title:Evolution of oxygen carrying blood proteins in response to high-altitude and low-oxygen conditions in deer mice (genus Peromyscus).This project is awarded under the Postdoctoral Research Fellowships in Biological Informatics Program for 2006. Insights into the genetic architecture enabling organisms to function under extreme conditions can significantly increase our understanding of the evolutionary processes responsible for the origin and maintenance of natural variation. The objectives of this research are to elucidate the molecular basis of physiological adaptations to high-altitude hypoxic conditions in deer mice (Peromyscus sp.). This interdisciplinary study will involve molecular genetic, biophysical, and biochemical analyses of naturally occurring variation in the genes that encode the alpha- and beta-globin subunits of hemoglobin. Analyses of DNA variation of the alpha- and beta-globin chains will be conducted to determine the role that selection has on fixing hemoglobin variation and to quantify how protein-protein interactions affect the genetic architecture of this molecule. Using protein models, computer analyses will predict how hemoglobin molecules will function under different oxygen conditions. Biochemical assays will be conducted to test these predictions. By integrating evolutionary analyses of DNA sequence variation and computer and in vitro analyses of the proteins, this research will provide a comprehensive analysis of hemoglobin structure and function. These data will provide testable predictions on how protein variation influences whole-organism respiratory physiology under different oxygen conditions. The post-doctoral fellow will work in the lab of Jay Storz at the University of Nebraska-Lincoln where she will be trained in the theory and methodology of molecular biophysics, biochemistry, and structural biology. By combining these skills with the fellow's expertise in molecular evolution, phylogenetics, and population genetics, this experience will enable her to develop her own research program focusing on integrative biology. In addition to research experience, the fellow will develop a course for biology students that will introduce them to the theory and methods of protein biophysical analyses.