System Biology of the Human SULT 1A Genes

人类 SULT 1A 基因的系统生物学

• 批准号: 6837397
• 负责人: MICHAEL E BRADLEY
• 金额: $ 4.4万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-01 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6837397
• 关键词: biochemical evolution; computational biology; computer assisted sequence analysis; functional /structural genomics; gene expression; genetic mapping; genetic regulation; genetic regulatory element; molecular biology information system; nucleic acid sequence; postdoctoral investigator; protein protein interaction; protein structure function; sulfotransferase; systematic biology; transcription factor

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.

描述（由申请人提供）：总体项目目标是实现硫代转移酶（SULT）1A基因家族的系统级智能，该智力已在灵长类动物中扩展，并与药物代谢，癌症，激素调节和神经递质生物学有关。该目标将通过在研究家族的进化史，转录调节和蛋白质网络中应用生物信息学和实验方法来实现。这些研究将立即受益于利用个体间遗传变异的努力，以提供遗传量身定制的药物。该项目还将在将来对系统进行更高级别的建模，以产生实用的治疗解决方案，以抑制硫化的不良影响，这目前是该领域的瘫痪问题。这项工作的具体目的是1）在系统基因学环境中检查家族的进化模型，并通过统计检测检测功能变化和保护的发作，2）模拟人类Sult 1a基因表达的调节控制，而3）以确定涉及人类Sult 1A酶的新型蛋白质相互作用。在追求这些目标的同时，申请人将参加实验室会议，参加与佛罗里达大学培训有关的领域的研讨会，并选择了课程讲座。