Evolution of Developmental Regulatory Pathways

发育监管途径的演变

• 批准号: 8089540
• 负责人: RONALD E ELLIS
• 金额: $ 27.52万
• 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/8089540
• 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

DESCRIPTION (provided by applicant): The advent of genome sequencing restored evolutionary studies to a central place in biomedical research, since they are essential for interpreting 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.

描述（由申请人提供）：基因组测序的出现将进化研究恢复到生物医学研究的中心位置，因为它们对于解释模式生物中调控途径的信息如何应用于人类至关重要。这个领域的一个大问题是这些调控途径是如何进化的。有三个因素使线虫成为研究进化过程的优秀模型。首先，秀丽隐杆线虫是生殖生物学、细胞死亡、微rna、衰老和其他医生感兴趣的主题研究的主要焦点。其次，用于研究这些动物的基因组和功能工具非常出色。第三，优秀的品质是可以学习的。例如，线虫C. elegans和C. briggsae的雌雄同体发育是独立进化的。本提案描述了使用遗传和分子技术来了解C. briggsae雌雄同体发育如何演变的实验。由于雌雄同体线虫调节性别决定途径以使XX动物产生精子，因此这一特性对于了解调节途径在进化过程中如何变化是理想的。到目前为止，我们已经鉴定并克隆了使XX动物发育为雌雄同体的glf-1和glf-1下游的glf-2。这些基因对C. briggsae来说是新发现的，对于了解雌雄同体的发育起源至关重要。这个项目有三个具体目标。首先是筛选与GLF-1相互作用的蛋白质。由于GLF-1是一类新的F-box蛋白的成员，它的结合伙伴是理解它如何控制发育的关键。第二个目标是克隆和表征glf-2，这是一种新的性别决定基因，在glf-1的下游作用，促进精子发生。第三个目标涉及使用增强子和抑制子筛选来识别在该途径中起作用的其他基因，并表征这些基因。这些基因将成为未来克隆和分子分析的候选基因。许多基因合作调节人类如何发展和对抗疾病。美国国立卫生研究院资助的大部分基础研究都是通过在简单生物身上研究这些基因是如何工作的。这个项目将阐明基因的功能在进化过程中是如何变化的，这可以帮助科学家选择研究哪些生物，并避免对它们的医学意义进行错误的推断。