Evolution of Developmental Regulatory Pathways

发育监管途径的演变

基本信息

批准号：
8296612
负责人：
RONALD E ELLIS
金额：
$ 13.65万
依托单位：
UNIV OF MED/DENT NJ-SCH OSTEOPATHIC MED
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8296612
关键词：
Address Aging Animal Model Animals Basic Science Binding Biomedical Research Birds CCL4 gene Caenorhabditis elegans Cell Death Chromosome Mapping Cloning Complex Data Development Disease Employee Strikes Enhancers Evolution F-Box Proteins Female Fogs Funding Future Genes Genetic Genetic Screening Genome Habits Hermaphroditism Homologous Gene Human Influentials Learning Medical MicroRNAs Mind Molecular Analysis Molecular Cloning Molecular Genetics Natural Selections Nematoda Partner in relationship Pathway interactions Phylogeny Physicians Play Process Protein Binding Proteins RNA Interference Regulator Genes Regulatory Pathway Reproductive Biology Role SKP Cullin F-Box Protein Ligases Scientist Single Nucleotide Polymorphism Map Spermatogenesis Structure Study models System Techniques Textbooks Time Transgenic Animals United States National Institutes of Health Ursidae Family Wing Work fighting functional genomics gene function genome sequencing interest member mutant novel research study sex determination sperm cell theories tool trait

项目摘要

The advent of genome sequencing restored evolutionary studies to a central place in biomedical research, since they are essential for interpretting how information about regulatory pathways in model organisms might apply to humans. One of the big questions in the field is how these regulatory pathways evolve. Three factors make nematodes an excellent model for studying evolutionary processes. First, C. elegans is a major focus of study about reproductive biology, cell death, micro-RNAs, aging, and other subjects of interest to physicians. Second, the genomic and functional tools available for working with these animals are outstanding. Third, excellent traits are available for study. For example, hermaphrodite development evolved independently in the nematodes C. elegans and C. briggsae. This proposal describes experiments that use genetic and molecular techniques to learn how hermaphroditic development evolved in C. briggsae. Since hermaphrodite nematodes modulate the sex-determination pathway to allow XX animals to make sperm, this trait is ideal for learning how regulatory pathways change during evolution. So far, we have identified and cloned glf-1, which causes XX animals to develop as hermaphrodites, and glf-2, which acts downstream of glf-1. These genes are novel to C. briggsae, and critical to learning how hermaphrodite development originated. This project has three specific aims. The first is to screen for proteins that interact with GLF-1. Since GLF-1 is a member of a new class F-box proteins, its binding partners are the key to understanding how it controls development. The second aim is to clone and characterize glf-2, a new sex-determination gene that acts downstream of glf-1 to promote spermatogenesis. The third aim involves the use of enhancer and suppressor screens to identify additional genes that act in this pathway, and to characterize these genes. These genes would be candidates for future cloning and molecular analyses. Many genes cooperate to regulate how humans develop and fight disease. Much of the basic research funded by the NIH focuses on how these genes work by studying them in simple creatures. This project will elucidate how the functions of genes change during evolution, which could help scientists choose which creatures to study, and avoid mistaken inferences about their medical significance.

基因组测序的出现使进化研究恢复到了中心地位生物医学研究，因为它们对于解释有关信息的方式至关重要模式生物中的调控途径可能适用于人类。大的之一该领域的问题是这些监管途径如何演变。三个因素使线虫成为研究进化的优秀模型流程。首先，线虫是生殖生物学、细胞死亡、微小RNA、衰老以及医生感兴趣的其他主题。其次，可用于研究这些动物的基因组和功能工具非常出色。第三，优秀的品质可供学习。例如，雌雄同体线虫 C. elegans 和 C. briggsae 的发育是独立进化的。该提案描述了使用遗传和分子技术来了解 C. briggsae 的雌雄同体发育是如何进化的。由于雌雄同体线虫调节性别决定途径，使 XX 动物能够对于精子来说，这种特征非常适合了解进化过程中调控途径如何变化。到目前为止，我们已经鉴定并克隆了glf-1，它导致XX动物发育为雌雄同体，以及glf-2，其作用于glf-1的下游。这些基因对于 C 来说是新颖的。 briggsae，对于了解雌雄同体的发育起源至关重要。该项目有三个具体目标。第一个是筛选与以下物质相互作用的蛋白质： GLF-1。由于 GLF-1 是新型 F-box 蛋白的成员，因此其结合伙伴是理解它如何控制发展的关键。第二个目标是克隆和表征glf-2，一种新的性别决定基因，作用于glf-1下游促进精子发生。第三个目标涉及增强子和抑制子的使用筛选以识别在此途径中起作用的其他基因，并表征这些基因基因。这些基因将成为未来克隆和分子分析的候选基因。许多基因共同调节人类的发育和对抗疾病的方式。大部分的美国国立卫生研究院 (NIH) 资助的基础研究重点是通过研究这些基因如何发挥作用在简单的生物中。该项目将阐明基因功能如何变化在进化过程中，这可以帮助科学家选择要研究的生物，以及避免对其医学意义的错误推断。