Causes and consequences of microbe-mediated asexuality

微生物介导的无性繁殖的原因和后果

基本信息

批准号：
10714424
负责人：
Amelia Ryan Isis Lindsey
金额：
$ 35.62万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10714424
关键词：
Appearance Arthropods Asexual Reproduction Bacteria Bacterial Proteins Biological Models Biology Cell division Cellular biology Creativeness Defect Degenerative Disorder Development Drosophila genus Drug resistance Environment Eukaryota Evolution Fertility Gene Pool Genetic Genetic Variation Genomic approach Genomics Goals Health Human Inherited Insecta Interdisciplinary Study Link Malignant Neoplasms Maps Mediating Meiosis Microbe Mitosis Mitotic Modeling Molecular Organism Parthenogenesis Pathogenesis Pathogenicity Ploidies Process Proteins Quantitative Trait Loci Reproduction Reproductive Biology Research Rickettsia Sex Functioning Sexual Reproduction System Wolbachia Yeasts asexual asexuality comparative genomics forward genetics genome sequencing invention microbial novel novel therapeutics pathogen reproductive sex symbiont theories trait tumor

项目摘要

Project Summary Sexual reproduction evolved more than one billion years ago, shortly after the appearance of eukaryotes. Sex is theorized to be an important aspect of creating genetic variation, adapting to new environments, and in removing disadvantageous traits from the gene pool. Despite this, many eukaryotes have reverted to asexual reproductive strategies. Importantly, such transitions to asexual reproduction have huge evolutionary impacts: we see regular examples of this in the rapid spread of invasive, pathogenic, and drug-resistant organisms. Unfortunately, such transitions are notoriously difficult to mechanistically interrogate due to their lack of experimental tractability and the fact that many reversions to asexuality are quite ancient. However, arthropods are rich in recently acquired vertically inherited microbes (e.g., Wolbachia, Rickettsia, and Cardinium) that convert their arthropod hosts to asexual reproduction. So-called “parthenogenesis induction” has been reinvented multiple times across these bacteria and relies on microbial mechanisms for impacting host meiosis or mitosis to alter ploidy. We can manipulate these recently asexual lineages in the lab to mechanistically define the cell biology of asexual reproduction. Furthermore, because there are numerous independent transitions to microbe-mediated asexuality, and lineages will slowly undergo a loss of sexual function, we can use this system to track the genomic and mechanistic consequences of lost sex. The long-term goal of my lab is to link mechanistic processes of mitosis, meiosis, and reproduction to long-term organismal and genomic consequences. This proposal describes my lab’s research goals across the next five years, which include: (1) mechanistically characterizing bacterial proteins mediating asexual reproduction, (2) identifying mitotic- and meiotic- effector proteins across diverse bacteria and reproductive biologies, and (3) using forward genetics to map the genomic consequences of lost sex. Specifically, our creative interdisciplinary research plan integrates genomic approaches (e.g., genome sequencing, comparative genomics, quantitative trait loci mapping), molecular approaches in non-model organisms, and genetics in tractable model systems (e.g., yeast, Drosophila). We will build on our recent discovery of the first putative asexuality inducing bacterial effector proteins to broadly define how microbes have evolved to manipulate mitosis and meiosis, and disentangle the causes of reproductive switches from the consequences. In addition to the broad significance of reproduction, these systems afford new opportunities to understand fundamental aspects of cell biology that underly many human-health relevant processes. For example, defects in mitosis are typical of certain degenerative conditions and cancers, and changes in ploidy significantly contribute to fungal pathogenesis and drug resistance. Our focus on novel mechanisms for altering reproduction and cell division will support the development of new therapeutic avenues across a range of systems.

项目概要有性生殖是在十亿多年前，在真核生物出现后不久就进化出来的。理论上被认为是创造遗传变异、适应新环境以及在尽管如此，许多真核生物已经恢复了无性。重要的是，这种向无性繁殖的转变具有巨大的进化影响：我们在入侵性、致病性和耐药性生物体的快速传播中经常看到这种情况的例子。不幸的是，由于缺乏足够的信息，这种转变很难机械地询问。实验上的易处理性以及许多无性繁殖的历史相当悠久。然而，节肢动物。富含最近获得的垂直遗传微生物（例如沃尔巴克氏体、立克次氏体和卡迪氏菌）将其节肢动物宿主转化为无性繁殖。在这些细菌中进行了多次改造，并依赖于影响宿主减数分裂的微生物机制我们可以在实验室中机械地操纵这些最近的无性谱系。定义无性繁殖的细胞生物学此外，因为有许多独立的细胞。转变为微生物介导的无性生殖，并且谱系将慢慢丧失性功能，我们可以使用这个系统来追踪失去性行为的基因组和机制后果是我实验室的长期目标。是将有丝分裂、减数分裂和繁殖的机械过程与长期的生物学和基因组联系起来该提案描述了我的实验室未来五年的研究目标。包括：(1) 介导无性繁殖的细菌蛋白的机制表征，(2) 识别不同细菌和生殖生物学中的有丝分裂和减数分裂效应蛋白，（3）使用正向遗传学来绘制失去性的基因组后果，具体来说，是我们的创造性。跨学科研究计划整合基因组方法（例如基因组测序、比较基因组学、数量性状基因座作图）、非模式生物的分子方法以及遗传学我们将建立在我们最近发现的第一个假定的模型系统的基础上。无性诱导细菌效应蛋白广泛定义微生物如何进化来操纵有丝分裂和减数分裂，并将生殖转换的原因与后果分开。对于生殖的广泛意义，这些系统提供了新的机会来理解基本原理许多人类健康相关过程的细胞生物学方面，例如有丝分裂的缺陷。是某些退行性疾病和癌症的典型特征，倍性的变化显着有助于我们专注于改变生殖和细胞的新机制。该部门将支持跨一系列系统开发新的治疗途径。