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Modular design of synthetic transcriptional regulators

合成转录调节因子的模块化设计

基本信息

批准号：
7327765
负责人：
ASEEM Z ANSARI
金额：
$ 24.49万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7327765
关键词：
Animal Model Binding Binding Sites Biological Biology Cardiac Cell Line Cells Chemicals Chemistry Class Complement Cultured Cells DNA DNA Binding DNA Binding Domain DNA Sequence Defect Development Diabetes Mellitus Disease Docking Drosophila genus Embryo Family Gene Expression Gene Expression Regulation Gene Targeting Generations Genes Genetic Transcription Genome Goals Heart Life Ligands Link Malignant Neoplasms Measures Membrane Modeling Molecular Conformation Molecular Medicine Monitor Nature Nylons Organism Pathway interactions Pattern Peptides Play Pliability Property Recruitment Activity Reporter Research Personnel Role Signal Transduction Site Specificity System Testing Therapeutic Agents Time Transcriptional Regulation Ursidae Family Work base cell type combinatorial cooperative study design desire driving force genetic regulatory protein in vivo insight member next generation novel novel therapeutics programs promoter response small molecule success transcription factor

项目摘要

ell fate is determined by sets of genes that are expressed in a programmed manner during development and cellular differentiation. Often, in diseases as diverse as diabetes and cancer, malfunctioning transcriptional regulators produce aberrant patterns of gene expression that are at the heart of the ailment. How regulatory proteins find their binding sites and regulate their targeted genes remains a central question n the field. We combine chemical and biological approaches to study otherwise intractable features of transcriptional regulators. We utilize sequence-specific DNA binding compounds (polyamides) to target specificDMA sequences, and they can be readily modified to bear a rich array of functional modules. In the proposed work, we will elucidate the basis of cooperative DNA binding by Extradenticle and Ultrabithorax, two highly conserved developmental regulators. We will apply that understanding to develop precisely tailored synthetic regulators that target genes cooperatively with cell-type specific transcription factors. Finally, we will test the ability of our artificial transcription factors to regulate genes in cells and in living organisms. The ultimate goal of our work is to generate small molecules that can regulate the expression oftargeted genes in a desired manner. As designer transcription factors, these molecules will have tremendous value in dissecting transcriptional networks that govern cell fate and disease. The aslo have potential as therapeutic agents for a variety of diseases that are caused by aberrant transcriptional regulation.

一个人的命运是由一组基因决定的，这些基因在发育过程中以程序化的方式表达