Collaborative Research: Microbiota Role in Intestinal Regeneration

对于为什么有些动物可以再生某些组织或器官，而其他物种则不能，我们知之甚少。这项研究探索了一种新的生物--海参--海参的再生。这些动物具有令人难以置信的再生丢失结构的能力，这项研究将重点放在肠道的再生上。近年来，与生物体相关的微生物环境或微生物区系已被证明在生物体的发育和正常功能中发挥着重要作用。本项目旨在确定微生物区系在肠道再生过程中的可能作用。在这项研究中，将对与再生肠道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正在调节肠道再生。此外，该项目还为本科生提供“动手”研究培训，以此作为指导他们走向科学研究事业的一种方式，并有助于增加科学界的多样性。在脊椎动物和无脊椎动物中，消化道内的微生物区系已被证明可以调节能量代谢和免疫。然而，对它们在器官发生中的作用，特别是在器官丢失或损伤后新器官的再生中所起的作用，人们知之甚少。这项提议旨在扩大我们对微生物区系在发育和再生过程中的作用的了解。该提案汇集了两位拥有不同专业领域的研究科学家，他们将联合起来，重点研究海参肠道微生物区系的特征及其在海参消化道再生中的作用。为了确定微生物区系的可能影响，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区系分析。拟议的项目将：(1)描述两种不同种类的海参的肠道微生物区系，它们生活在不同的环境中，使用不同的摄食方式，并确定肠道再生期间微生物区系的时空变化。(2)通过使用抗生素和抗真菌药物对微生物区系进行修饰，确定微生物区系的作用。(3)通过对正常动物和用特定抗生素处理的再生动物进行转录转录分析，鉴定正常动物和再生动物中受微生物区系控制的宿主基因。提案的结果将是对微生物区系如何调节肠道再生的清楚描述，对在这一过程中发挥主要作用的物种和参与这一过程的目标基因的特征。这一奖项反映了NSF的法定使命，并已被认为值得支持，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。

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.