Evolution of Developmental Regulatory Pathways

发育监管途径的演变

• 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
• 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

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.

基因组测序的出现恢复了进化研究的中心地位， 生物医学研究，因为它们是必不可少的解释如何信息， 模式生物中的调节途径可能适用于人类。其中一个大 该领域的问题是这些调控途径如何演变。 三个因素使线虫成为研究进化的极好模型 流程.第一，C.线虫是生殖生物学、细胞生物学、 死亡，微RNA，衰老和其他医生感兴趣的主题。二是 可用于研究这些动物的基因组和功能工具非常出色。 第三，优秀的性状可供研究。例如，雌雄同体 线虫C.和秀丽隐杆线虫C.布里格塞 该提案描述了使用遗传和分子技术的实验， 了解C.布里格塞因为雌雄同体 线虫调节性别决定途径，使XX动物 精子，这种特性是学习如何调节途径在进化过程中变化的理想选择。 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 雌雄同体和GLF-2，其作用于GLF-1的下游。这些基因对C. briggsae，并且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。第一种是筛选与蛋白质相互作用的蛋白质， GLF-1。由于GLF-1是一类新的F盒蛋白，其结合伴侣是 这是理解它如何控制发育的关键。第二个目标是克隆和 描述了一个新的性别决定基因glf-2的特征，该基因作用于glf-1的下游， 促进精子发生。第三个目的涉及使用增强子和抑制子 筛选以鉴定在该途径中起作用的其他基因，并表征这些基因。 基因.这些基因将是未来克隆和分子分析的候选基因。许多基因共同调节人类如何发育和对抗疾病。大部分 由美国国立卫生研究院资助的基础研究主要集中在研究这些基因是如何工作的 在简单的生物中。这个项目将阐明基因的功能是如何变化的 这可以帮助科学家选择要研究的生物， 避免对它们的医学意义做出错误的推断。