System Biology of the Human SULT 1A Genes

描述(由申请者提供)：总体项目目标是实现磺基转移酶(Sult)1A基因家族的系统级智能，该基因家族已在灵长类动物中扩大，并与药物代谢、癌症、激素调节和神经递质生物学有关。这一目标将通过应用生物信息学和实验方法来研究该家族的进化史、转录调控和蛋白质网络来实现。这些研究将立即有利于在提供基因定制药物方面利用个体间基因变异的努力。该项目还将在未来对该系统进行更高级别的建模，以产生实用的治疗方案，以抑制磺化的不良影响，目前磺化是该领域的一个令人瘫痪的问题。这项工作的具体目标是1)在系统基因组学的背景下检查该家族的进化模型，并通过统计检验检测功能变化和保守的事件，2)模拟人类sult1A基因表达的调控，以及3)确定涉及人类sult1A酶的新的蛋白质相互作用。在追求这些目标的同时，申请人将参加实验室会议，并参加与他在佛罗里达大学的培训有关的领域的研讨会和选定的课程讲座。

DESCRIPTION (provided by applicant): The overall project goal is to achieve system-level intelligence of the sulfotransferase (SULT) 1A gene family that has expanded in primates and been linked to drug metabolism, cancer, hormone regulation, and neurotransmitter biology. The goal will be accomplished by applying bioinformatic and experimental methods in studying the evolutionary history, transcriptional regulation, and protein network of the family. These studies will immediately benefit efforts to exploit inter-individual genetic variation in offering genetically tailored medicine. This project will also enable higher-level modeling of the system in the future that should yield practical therapeutic solutions for repressing the ill-effects of sulfonation, which is currently a paralyzing issue in the field. The specific aims of this work are 1) to examine the family's evolutionary model in a phylogenomics context and detect episodes of functional change and conservation with statistical tests, 2) to model the regulatory controls of human SULT 1A gene expression, and 3) to determine novel protein interactions involving the human SULT 1A enzymes. While pursuing these aims the applicant will engage in laboratory meetings and attend seminars and selected course lectures on areas related to his training at the University of Florida.