CAREER: Establishing the Drosophila proventriculus as a model symbiosis organ

该奖项的全部或部分资金来自《2021年美国救援计划法案》(公法117-2)。大多数动物的肠道中保留着某些类型的细菌，这些细菌通过改善饮食营养和调节免疫系统来帮助动物。微生物协会在昆虫中尤其重要，昆虫对农业、生态和人类健康至关重要，包括蜜蜂等传粉者、壁虫和果蝇等害虫以及蚊子和扁虱等病媒。昆虫如何招募和维持它们喜欢的细菌，在很大程度上是未知的，因为宿主用来调节定殖性的特定基因和分子。这项拟议的研究旨在通过识别这些基因和分子以及特定的宿主细胞如何调控它们来弥合这一知识差距。由于昆虫在生态、农业和公共卫生中的关键作用，拟议的研究结果可能会通过开发共生细菌的用途来帮助和控制昆虫而产生重大影响。此外，哺乳动物之间基因功能的高度保守意味着在昆虫上的发现可能适用于其他动物，包括脊椎动物。这笔赠款的更广泛影响还包括在公立学校开发和实施实践和在线微生物学课程。对于动物来说，关于构建和维护共生生物宿主组织的精确发育遗传机制，以及宿主是否可以利用某些细菌来控制其他细菌，存在着知识缺口。长期以来，果蝇一直是动物发育遗传学的主力，拥有无与伦比的可公开获得的具有明确基因扰动的基因库资源，以及整个动物界广泛的遗传保护。PI在果蝇前肠的一个精确而未被研究的部分发现了形成粘附性多物种群落的共生细菌，这为将果蝇遗传学应用于不同肠道细菌与宿主之间的共生研究提供了一个变革性的机会。这项研究将根据支持细菌的苍蝇基因来定义果蝇的共生器官。宿主在分泌和免疫方面的遗传途径将通过定量细胞生物学、微生物学和基因组学方法以及同位素比质谱学方法进行评估，同位素比值质谱仪将用于测量宿主和细菌之间的营养交换。这将通过提供候选基因和发展计划来推动该领域的发展，以发现其他昆虫和动物，甚至可能是人类的共生生态位。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。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).Most animals maintain certain types of bacteria in their gut that aid the animal by improving the nutrition of the diet and modulating the immune system. Microbial associations are particularly important in insects, which are critically important to agriculture, ecology, and human health, including pollinators such as bees, pests such as squash bugs and fruit flies, and disease vectors such as mosquitos and ticks. How insects recruit and maintain their preferred bacteria is largely unknown in terms of the specific genes and molecules the host uses to regulate colonization. The proposed research aims to close this knowledge gap by identifying these genes and molecules and how specific host cells regulate them. Due to critical roles of insects in ecology, agriculture, and public health, outcomes of the proposed research could have major impacts by developing uses of symbiotic bacteria to aid and control insects. Furthermore, the high conservation of gene function across mammals means discoveries in insects could apply to other animals, including vertebrates. Broader impacts of this grant also include development and implementation of hands-on and online microbiology curricula in public schools.Across animals, there is a knowledge gap around the precise developmental genetic mechanisms that construct and maintain the host tissues that house symbiotic organisms as well as whether a host can use certain bacteria to control others. Drosophila has long been a workhorse of animal developmental genetics, with unparalleled resources of publicly available genetic stocks with defined gene perturbations, and the wide genetic conservation across the animal kingdom. The PI’s discovery of symbiotic bacteria that form an adherent, multispecies community in a precise and understudied section of the Drosophila foregut presents a transformative opportunity to apply Drosophila genetics to the study of symbiosis between diverse gut bacteria and the host. This research will define the Drosophila symbiotic organ in terms of the fly genes that support the bacteria. Host genetic pathways, in secretion and immunity will be evaluated by quantitative cell biology, microbiology, and genomics approaches as well as by isotope ratio mass spectrometry, which will be used to measure nutrient exchange between host and bacteria. This will advance the field by providing candidate genes and developmental programs to discover symbiotic niches in other insects and animals, possibly even humans.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.