CAREER: Experimental manipulation of host-microbe associations to reveal key features promoting symbiosis
职业:宿主-微生物关联的实验操作,揭示促进共生的关键特征
基本信息
- 批准号:2239595
- 负责人:
- 金额:$ 106.76万
- 依托单位:
- 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:2023-03-01 至 2028-02-29
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Many animals rely on microbial symbionts to help them gain sufficient nutrients, provide protection from predators and pathogens, or allow them to live in otherwise inhospitable environments. Studying these relationships can be difficult as it is often impossible to separate the microbes from their host. As a result, understanding of the mechanisms that underly these relationships has been limited by the inability to manipulate both host and symbiont independently. Kissing bugs are insects that feed exclusively on vertebrate blood and serve as host to symbiotic bacteria, that help them successfully develop and reproduce. These bacteria also can be cleared from the kissing bugs and infected with new bacteria. The symbiont bacteria can also be grown outside of the insect and can be genetically altered. This system, thus, provides a unique opportunity to experimentally manipulate the host and symbiont, to identify and characterize factors that support the symbiosis. The research will focus on genes involved in symbiont colonization of the host, host and symbiont genes involved in the exchange of nutrients, and interactions of the host immune system and the symbiont. Given the ubiquity of animal-microbe symbioses, this research will illuminate mechanisms that may govern host-microbe interactions in other less-tractable systems. Along with the proposed research, this project will also provide research experience and training to high school teachers. This experience will be paired with curriculum development to incorporate host-microbe interactions into the teachers’ classrooms. Experimental manipulation of host-microbe systems has been limited by inability to separate highly integrated partners or difficulties disentangling the effects of individual members in highly complex communities. Triatomine kissing bugs harbor essential symbionts in their gut which are environmentally acquired each generation, allowing for generation of bacteria-free, axenic insects, which can then be experimentally inoculated with bacteria. This work leverages the unique features of this system – ability to generate axenic and gnotobiotic insects, low-complexity microbiomes, and molecular tools – to delineate the mechanistic basis of symbiosis. Transposon mutagenesis will be used to identify genes in the symbiont Rhodococcus rhodnii that are essential for symbiosis followed by generation of knockout strains of R. rhodnii lacking symbiosis-promoting genes. Knockout strains will be used for bioassays to characterize the role of the gene-of-interest in the relationship. The role of the host immune system in regulating bacterial abundance will be assessed, examining both humoral and cellular immune responses to symbionts. Lipid metabolism genes including fatty acid synthases and fatty acid CoA reductases have been identified as differentially expressed in axenic and gnotobiotic insects. Liquid chromatography and mass spectroscopy will be applied to understand how symbiotic bacteria shape the lipidome of kissing bugs while silencing of specific lipid genes will reveal the role of these genes in lipid metabolism and host fitness. The proposed work will shed new light on the evolution of host-symbiont interactions and serve as a framework for exploring systems which are less amenable to experimental manipulation.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.
许多动物依靠微生物共生体来帮助它们获得足够的营养,提供对捕食者和病原体的保护,或者允许它们生活在原本不适宜居住的环境中。研究这些关系可能很困难,因为通常不可能将微生物从宿主中分离出来。因此,由于无法独立操纵宿主和共生体,人们对这些关系背后的机制的理解一直受到限制。接吻臭虫是一种昆虫,专门以脊椎动物的血液为食,并作为共生细菌的宿主,帮助它们成功发育和繁殖。这些细菌也可以从接吻的虫子身上清除出来,并感染上新的细菌。共生菌也可以在昆虫外生长,并可以进行基因改造。因此,这个系统提供了一个独特的机会来实验地操纵宿主和共生体,以识别和表征支持共生的因素。这项研究将集中在寄主共生体定植的基因,寄主和共生体参与营养交换的基因,以及宿主免疫系统和共生体的相互作用。考虑到动物-微生物共生的普遍存在,这项研究将阐明在其他不太容易处理的系统中可能支配宿主-微生物相互作用的机制。除了拟议的研究,该项目还将为高中教师提供研究经验和培训。这种体验将与课程开发相结合,将宿主与微生物的互动纳入教师的课堂。寄主-微生物系统的实验操作一直受到无法分离高度整合的伙伴或难以在高度复杂的社区中分离单个成员的影响的限制。接吻三聚氰胺的昆虫的肠道中含有重要的共生体,这些共生体是每一代人在环境中获得的,从而产生了无细菌、无菌的昆虫,然后可以通过实验接种细菌。这项工作利用这一系统的独特功能--能够产生无菌和共生昆虫、低复杂性微生物群和分子工具--来描绘共生的机制基础。转座子突变将被用来鉴定罗德尼红球菌共生菌中对共生至关重要的基因,随后将产生缺乏共生促进基因的罗得尼红球菌敲除菌株。基因敲除菌株将被用于生物检测,以表征相关基因在这种关系中的作用。将评估宿主免疫系统在调节细菌丰度方面的作用,检查对共生体的体液和细胞免疫反应。脂肪代谢基因,包括脂肪酸合成酶和脂肪酸辅酶A还原酶,已被鉴定为在无菌昆虫和共生昆虫中差异表达。研究人员将利用液相色谱和质谱仪来了解共生细菌如何塑造接吻臭虫的脂体,而沉默特定的脂类基因将揭示这些基因在脂类代谢和宿主适合性中的作用。这项拟议的工作将为宿主-共生体相互作用的演变提供新的线索,并作为探索不太适合实验操作的系统的框架。这一奖项反映了NSF的法定使命,并通过使用基金会的智力优势和更广泛的影响审查标准进行评估,被认为值得支持。
项目成果
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