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: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=757196
• 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，是维生素的生成和吸收以及营养物质新陈代谢的重要器官。在这一过程中的一个工具是肠道微生物组(肠道中所有微生物的集合)，它在我们的消化道找到自己的家。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身体内的一个额外的重要器官，因此是哺乳动物生理的组成部分。有趣的是，微生物群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，是独特和独特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使我们有可能同时分析这些复杂群落中的病毒、细菌、原生动物和真菌基因组的组成。尖端的下一代测序不仅能够揭示这一高度复杂的微生物集合中单个微生物成员的身份，而且进一步能够表征在单个成员中活跃表达的基因。基于这些信息量非常大的数据集，可以推断出从整个社区到其中的个别成员的功能适应。我们最近发现肌肉毛滴虫是一种新的原生动物物种，是健康小鼠肠道的永久居住者。T.Mu很像它最接近的人类近亲脆弱链霉菌，据报道在老鼠和人类身上有很高的丰度和定殖率(根据群落的不同，从4%到40%不等)。摄取低至1000个提纯的T.u会导致在小鼠体内的长期定植和水平传播。细菌微生物群的变化是改变饮食、年龄增长、感染、环境和生活方式的结果，通常是通过这些因素对细菌群落的直接影响而实现的。T.Mu的转录组目前尚不清楚。通过测定肠道环境中结核分枝杆菌的基因表达谱，可以了解肠道微生物稳定定植肠道的机制和途径，成为肠道微生物群的一员。在这个项目中，我们的目标是了解环境因素，如肠道细菌微生物区系和粘膜免疫系统如何控制T.tu的基因表达，以使T.Mu在不断变化的环境中稳定适应。