Environmental control of gene expression in commensal protozoa

共生原生动物基因表达的环境控制

• 批准号: RGPIN-2019-04521
• 负责人: Mortha, Arthur
• 金额: $ 2.7万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=737679
• 关键词: Environmental; control; gene; expression; commensal

The gastrointestinal tract is the body's largest mucosal surface and an essential organ for the generation and absorption of vitamins and the metabolism of nutrients. An instrumental tool in this process is the intestinal microbiome (the collection of all microbes in our intestine), finding its home in our digestive tract. It is one of the largest and most diverse community of microbes vastly outnumbering the genetic information encoded by our body. These microbial communities are considered an additional vital organ within our body and are thus an integral part of the mammalian physiology. Interestingly the diversity of the microbiome has only recently begun to be uncovered and most strikingly, bacteria (unlike often anticipated) are not the only microbial kingdom in our intestines. Fungi, viruses, worms and protozoa are additional members of the microbiome and are parts of unique and distinct phylogenetic kingdoms. Our advancement in molecular DNA sequencing technologies opened the possibility to simultaneously analyze the composition of viral, bacterial, protozoan and fungal genomes within these complex communities. Cutting edge next-generation sequencing is not only able to uncover the identity of individual microbial members within this highly complex assembly of microorganism, but further to this enable the characterization of genes actively expressed within individual members. Based on these very informative data sets, functional adaptations can be extrapolated ranging from whole communities to even individual members therein. We recently identified Trichomonas musculis (T.mu), a new protozoan species, as a permanent inhabitant of the healthy mouse intestine. T.mu, much like its closest human relative Dientameba fragilis have a reportedly high abundance an colonization efficiency in mice and humans (ranging from 4-40%, depending on the community). Uptake of as little as 1000 purified T.mu results in a live-long colonization and horizontal transmission in mice. Changes in the bacterial microbiome are the result of changing diets, increase in age, infections, the environment and life style, often accomplished through direct impact of these factors on the bacterial community. The transcriptome of T.mu is currently unknown. Determining the gene expression profile of T.mu within the intestinal environment could inform about mechanisms and pathways, utilized to stably colonize our gut and become a member of the intestinal microbiome. Within this project, we aim to understand how environmental factors like the intestinal bacterial microflora and the mucosal immune system control the gene expression of T.mu to allow stable adaptation of T.mu in the context of a changing environment.

胃肠道是人体最大的粘膜表面，也是维生素生成和吸收以及营养物质代谢的重要器官。这个过程中的一个工具是肠道微生物组（我们肠道中所有微生物的集合），在我们的消化道中找到它的家。它是最大和最多样化的微生物群落之一，其数量远远超过我们身体编码的遗传信息。这些微生物群落被认为是我们体内的一个额外的重要器官，因此是哺乳动物生理学的一个组成部分。有趣的是，微生物组的多样性直到最近才开始被发现，最引人注目的是，细菌（与通常预期的不同）并不是我们肠道中唯一的微生物王国。真菌、病毒、蠕虫和原生动物是微生物组的额外成员，并且是独特和不同的系统发育王国的一部分。我们在分子DNA测序技术方面的进步为同时分析这些复杂群落中病毒、细菌、原生动物和真菌基因组的组成提供了可能性。尖端的下一代测序不仅能够揭示这种高度复杂的微生物组装体中单个微生物成员的身份，而且还能够表征单个成员中活跃表达的基因。基于这些非常翔实的数据集，可以推断出从整个社区甚至其中的个体成员的功能适应。我们最近确定了毛滴虫musculis（T.mu），一个新的原生动物物种，作为一个永久居民的健康小鼠肠道。T.mu，很像其最接近的人类亲戚Dientameba fragilis，据报道在小鼠和人类中具有高丰度和定殖效率（范围为4- 40%，取决于社区）。摄入少至1000个纯化的T.mu会导致小鼠体内的终生定植和水平传播。细菌微生物组的变化是改变饮食、年龄增长、感染、环境和生活方式的结果，通常通过这些因素对细菌群落的直接影响来实现。T.mu的转录组目前未知。确定T.mu在肠道环境中的基因表达谱可以提供有关机制和途径的信息，用于稳定地定植在我们的肠道中并成为肠道微生物组的成员。在这个项目中，我们的目标是了解环境因素如肠道细菌菌群和粘膜免疫系统如何控制T.mu的基因表达，以使T.mu在不断变化的环境中稳定适应。