CAREER: The genetic and developmental basis of body size evolution in nematodes

职业：线虫体型进化的遗传和发育基础

基本信息

批准号：
2238788
负责人：
Gavin Woodruff
金额：
$ 96.48万
依托单位：
University of Oklahoma Norman Campus
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2023
资助国家：
美国
起止时间：
2023-03-15 至 2028-02-29
项目状态：
未结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2238788&HistoricalAwards=false
关键词：
CAREER genetic developmental basis body

项目摘要

The diversity among animal body sizes (from at least ants to elephants) is immense and demands explanation. Yet, the genetic and developmental changes that cause body size evolution remain unknown. The proposed work aims to address this problem by harnessing both long-established and cutting-edge genetic techniques in closely-related roundworm species with drastically different body sizes to identify the causes of body size variation. This work is important because we know larger roundworm species have larger cells than those of smaller species, and when the processes regulating cell size go awry, diseases such as cancer emerge. This work then has the potential to discover novel genes that control cell size and thus potential novel targets for cancer therapeutics. Beyond this, the research work described above will be integrated with multiple, established educational initiatives in the state of Oklahoma including: 1) The University of Oklahoma’s four-year undergraduate research experience program; 2) A multi-year summer research program for American Indian undergraduates; 3) A research experience for high school students summer program; and 4) A graduate-student led summer coding workshop. Additionally, an undergraduate developmental biology laboratory course will be developed where students will participate in the original research activities described above. The proposed work not only aims to make significant advances in understanding the evolution of body size and the genes underlying cell size variation, but this work also aims to connect multiple educational efforts with these research efforts to simultaneously advance both scientific knowledge and societal good.Understanding how developmental systems evolve to promote phenotypic diversity is a fundamental goal of biology. These systems include and regulate the morphogenetic fields, signaling factors, and differentiation decisions essential for the construction and ultimate form of a multicellular organism. Despite this, while gene regulatory networks have been painstakingly described in a handful of model systems, network architecture change is rarely connected to morphological divergence among species. How does genetic variation change developmental processes to cause divergent phenotypes? Over forty years of C. elegans genetics has revealed the developmental details of a canonical TGF-β signaling network that regulates body size in this species. C. inopinata is the sister species of C. elegans, and it is nearly twice as long in size as its highly-studied close relative. Here, the vast background knowledge of a long-standing model system will be integrated with a comparative approach to understand how network modification causes phenotypic divergence. This work will include: 1) The perturbation of TGF-β pathway activity in two species to determine how ancestral body size genes evolve to promote cell size divergence; 2) The generation and mapping of large-effect body size mutations in C. inopinata to discover novel genes driving cell size regulation; and 3) The characterization of tissue-specific cell size variation in mutants across development in two species. Not only will this work map genotypes to organismal phenotypes such as body size, but it will also show how genotypes influence cellular phenotypes to cause the emergence of such organismal phenotypes. The research work described above will be integrated with multiple, established educational initiatives in the state of Oklahoma to broaden the participation of students at all levels in scientific research.This project is jointly funded by the BIO-IOS-Developmental Systems Program and the Established Program to Stimulate Competitive Research (EPSCoR).This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

动物体大小之间的多样性（至少从蚂蚁到大象）是巨大的，需要解释。然而，导致体大小进化的遗传和发育变化仍然未知。拟议的工作旨在解决与近距离往返物种截然不同的round虫物种中长期和尖端的遗传技术，以识别体大小变异的原因。这项工作很重要，因为我们知道较大的round虫物种比较小物种的细胞更大，而且当过程调节细胞大小时，出现了诸如癌症之类的疾病。然后，这项工作有可能发现控制细胞大小的新基因，从而潜在的癌症治疗靶标。除此之外，上述研究工作还将与俄克拉荷马州的多个已建立的教育计划融合在一起，包括：1）俄克拉荷马大学的四年内科本科研究经验计划； 2）为美洲印第安人的多年夏季研究计划； 3）高中生暑期课程的研究经验； 4）一个研究生的LED LED夏季编码研讨会。此外，将开发一项本科生物学实验室课程，学生将参加上述原始研究活动。拟议的工作不仅旨在在理解身体大小的演变以及细胞大小变化的基因的发展方面取得重大进展，而且这项工作还旨在将多种教育努力与这些研究工作联系起来，以简单地促进科学知识和社会善良。理解发展系统如何发展以促进表型多样性是生物学的基本目标。这些系统包括和调节形态发生场，信号因子和分化决策对于多细胞生物的构建和最终形式所必需的。尽管如此，尽管基因调节网络在少数模型系统中进行了艰苦的描述，但网络架构的变化很少与物种之间的形态差异有关。遗传变异如何改变发育过程以引起发散表型？超过40年的秀丽隐杆线虫遗传学揭示了调节该物种体型的规范TGF-β信号网络的发展细节。 C. inopinata是秀丽隐杆线虫的姊妹物种，其大小几乎是其高度研究的亲戚的两倍。在这里，长期存在的模型系统的庞大背景知识将通过比较方法集成，以了解网络修改如何引起表型差异。这项工作将包括：1）两个物种中TGF-β途径活性的扰动，以确定祖先体大小基因如何进化以促进细胞大小的差异； 2）在c。Inopinata中，大型体型突变的产生和映射发现了驱动细胞大小调节的新型基因； 3）在两个物种中，突变体的组织特异性细胞大小变化的表征。该工作图基因型不仅会涉及体型等有机表型，而且还将显示基因型如何影响细胞表型引起这种有机表型的出现。上述研究工作将与俄克拉荷马州的多个已建立的教育计划集成，以扩大学生在各级参与科学研究中的参与。该项目由Bio-Oio-Oios开发系统计划和既定计划共同资助，并建立的计划既有竞争性研究（EPSCOR），以反映了NSF的构建范围，以反映NSF的范围。影响审查标准。