Collaborative Research: Microbiota Role in Intestinal Regeneration

为什么有些动物可以再生某些组织或器官，而另一些动物却不能，我们所知甚少。本研究探索了一种新的生物，海参Holothuria glaberrima的再生。这些动物具有令人难以置信的再生失去的结构的能力，这项研究将重点放在肠道的再生上。近年来，与生物体或微生物群相关的微生物环境已被证明在生物体的发育和正常功能中起着重要作用。该项目旨在确定微生物群在肠道再生过程中的可能作用。在这项研究中，将对与肠道再生相关的细菌和其他微生物进行表征，以确定是否以及哪些物种可能调节肠道再生。此外，该项目为本科生提供“动手”研究训练，作为指导他们走向科研事业的一种方式，并有助于增加科学界的多样性。消化道内的微生物群已被证明可以调节脊椎动物和无脊椎动物的能量代谢和免疫。然而，人们对它们在器官发生中的作用知之甚少，特别是在丢失或损伤后新器官的再生中。这一建议旨在扩展我们对微生物群在发育和再生过程中的作用的认识。该提案汇集了两位具有不同专业领域的研究科学家，他们将联合起来，专注于全息图肠道微生物群的特征及其在全息图消化道再生中的功能。为了确定微生物群可能产生的影响，将利用最先进的技术，包括RNA-Seq和16rRNA测序以及更传统的微生物群分析。拟开展的项目将：(1)对两种不同生存环境和摄食方式的海螺进行肠道菌群特征分析，确定其肠道再生过程中菌群的时空变化。(2)通过使用抗生素和抗真菌药物修饰微生物群来确定微生物群的作用。(3)通过对使用特定抗生素治疗的正常动物和再生动物进行转录组学分析，确定正常动物和再生动物中受微生物群控制的宿主基因。该提案的结果将是对微生物群如何调节肠道再生的清晰描述，对在该过程中起主要作用的物种的表征以及参与该过程的靶基因。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Little is known about why some animals can regenerate certain tissues or organs, while other species cannot. This research explores regeneration in a novel organism, the sea cucumber Holothuria glaberrima. These animals have an incredible ability to regenerate lost structures and this study will focus on the regeneration of the intestine. In recent years, the microbial environment associated with organisms, or microbiota, has been shown to play important roles in the development and proper function of an organism. This project aims to determine the possible role of the microbiota on the process of intestinal regeneration. For this study, the bacteria and other microorganisms that are associated with the regenerating intestine will be characterized to determine if and which species might be modulating intestinal regeneration. Moreover, the project provides "hands-on" research training to undergraduate students as a way of guiding them toward scientific research careers and help increase the diversity of the scientific community. The microbiota within the digestive tract has been shown to modulate energy metabolism and immunity in both vertebrate and invertebrate species. However, little is known of their role in organogenesis and in particular in the regeneration of new organs following loss or injury. This proposal aims to extend our knowledge of the microbiota role in developmental and regenerative processes. The proposal brings together two research scientists with different areas of expertise that will join forces to focus on the characterization of holothurian intestinal microbiota and its function in the regeneration of the holothurian digestive tract. To determine the possible effects of the microbiota, state of the art technology including RNA-Seq and 16rRNA sequencing together with more traditional microbiota analyses will be utilized. The proposed project will: (1) Characterize the intestinal microbiota of two different species of holothurians, that inhabit different environments and use different feeding methods and determine the spatial and temporal changes in the microbiota during intestinal regeneration. (2) Determine the role of the microbiota by modifying the microbiota using antibiotics and antifungal agents. (3) Identify the host genes that are under the control of the microbiota in normal and regenerating animals by performing transcriptomic analyses of normal and regenerating animals treated with specific antibiotic agents. The outcome of the proposal will be a clear description of how the microbiota modulates intestinal regeneration, a characterization of species that play a major role in the process and the target genes involved in the process.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.