Interpreting and Deploying Genomic Information During Animal Development

动物发育过程中基因组信息的解释和应用

• 批准号: 9923659
• 负责人: RICHARD S MANN
• 金额: $ 60.81万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-03 至 2021-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9923659
• 关键词: Address; Animals; Binding; Binding Sites; Biochemical; Biological; Cells; Code; DNA Sequence; Development; Disease; Distal; Drosophila genus; Epilepsy; Family; Gene Expression; Genes; Genetic; Genome; Genomics; Goals; Knowledge; Leg; Maps; Methods; Obesity; Specificity; Time; Work; experimental study; in vivo; personalized medicine; public health relevance; transcription factor

 DESCRIPTION (provided by applicant): The common theme underlying the questions being addressed in this proposal is how gene expression is controlled by cis-regulatory modules (CRMs) and the transcription factors that they bind during animal development. Answers to this question are becoming increasingly important in the emerging era of Personalized Medicine, since we now have the ability to sequence thousands of genomes and to identify changes in DNA sequences that correlate with diseases ranging from epilepsy to obesity. However, when changes in DNA sequence map to the non-protein coding portion of the genome, we are nearly helpless in interpreting these changes. This project will help bridge this gap in our knowledge by establishing methods to assess how the Hox family of transcription factors function in vivo. In the next several years, one goal is to extend what has been learned about Hox transcription factor specificity to a more in vivo level, in particular, to break the sequence code that allows these TFs to select biologically relevant binding sites in vivo. A second major goal is to understand at a deeper level how multiple transcription factors and CRMs coordinate with each other to regulate genes in the right cells and at the correct developmental time. For this last set of experiments, the focus is on how the proximo-distal axis of the Drosophila leg is established during development.

 描述（由申请人提供）：本提案中解决的问题的共同主题是基因表达如何受顺式调节模块（CRM）及其在动物发育过程中结合的转录因子的控制。在个性化医疗的新兴时代，这个问题的答案变得越来越重要，因为我们现在有能力对数千个基因组进行测序，并识别与癫痫和肥胖等疾病相关的DNA序列变化。然而，当DNA序列的变化映射到基因组的非蛋白质编码部分时，我们几乎无法解释这些变化。该项目将通过建立方法来评估Hox家族转录因子在体内的功能，从而帮助弥合我们知识中的这一差距。在接下来的几年里，一个目标是将已经了解到的关于Hox转录因子特异性的知识扩展到更体内的水平，特别是打破允许这些TF在体内选择生物学相关结合位点的序列密码。第二个主要目标是在更深层次上了解多种转录因子和CRM如何相互协调，以在正确的细胞和正确的发育时间调节基因。最后一组 实验的重点是如何在果蝇腿的proximo-distal轴是建立在发展过程中。