Evolution of Developmental Regulatory Pathways

发育监管途径的演变

• 批准号: 7869398
• 负责人: RONALD E ELLIS
• 金额: $ 27.8万
• 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/7869398
• 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; Research; 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型生物体中有关调节途径的信息至关重要。该领域的大问题之一是这些监管途径如何发展。三个因素使线虫成为研究进化过程的绝佳模型。首先，秀丽隐杆线虫是关于生殖生物学，细胞死亡，微RNA，衰老和其他感兴趣的学科的主要研究重点。其次，可用于与这些动物一起使用的基因组和功能工具非常出色。第三，可以研究出色的特征。例如，雌雄同体的发育在线虫秀丽隐杆线虫和briggsae中独立发展。该提案描述了使用遗传和分子技术来学习雌雄同体的发育如何在Briggsae中演变的实验。由于Hermaphrodite线虫可以调节性别确定的途径，使其允许XX动物制作精子，因此该特征是学习调节途径在进化过程中如何变化的理想选择。到目前为止，我们已经确定并克隆的GLF-1，这会导致XX动物作为Hermaphrodites发育，而GLF-2则在GLF-1的下游起作用。这些基因是对Briggsae的新颖的，并且对于学习雌雄同体的发育的产生至关重要。该项目具有三个特定的目标。首先是筛选与GLF-1相互作用的蛋白质。由于GLF-1是新类F-box蛋白的成员，因此其绑定伙伴是了解其控制开发方式的关键。第二个目的是克隆并表征GLF-2，这是一种新的性别确定基因，其作用于GLF-1的下游以促进精子发生。第三个目的涉及使用增强子和抑制器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。这些基因将是未来克隆和分子分析的候选者。许多基因合作以调节人类的发展和抗击疾病。 NIH资助的许多基础研究都集中在这些基因在简单生物中研究它们的工作方式。该项目将阐明基因在进化过程中的变化如何变化，这可以帮助科学家选择要研究的生物，并避免对其医学意义的推断。