CAREER: Modeling and Decoding Host-Microbiome Interactions in Gingival Tissue

人体内有许多不同但相互联系的微生物种群。 例如，细菌，病毒和真菌等微小生物的种群，肉眼无法看到。 有些微生物会让我们生病，而另一些则对我们的健康很重要。 它们彼此之间以及与周围组织之间的平衡或不平衡可以对个人的健康或疾病状态产生长期和广泛的影响。特别令人感兴趣的是口腔中的微生物群，因为它是致病（致病）细菌的潜在储存库。然而，人们对各种疾病与口腔微生物组的关系知之甚少。这个CAREER项目的研究目标是了解人类口腔组织，口腔微生物组之间的联系以及它们如何相互作用。这将通过创建人类牙龈（牙龈）组织系统的体外（实验室）模型来实现，该模型能够研究不同的微生物种群及其与整体人类健康的联系。 该项目的教育计划名为ResAx，其目标是提供一个工作模型，以解决低资源学术机构入学率下降的问题，该模型可以转移到其他研究领域（即，医疗器械、蛋白质工程）。多学科研究项目将提供机会，扩大研究和教育的本科生就读于BME课程在马萨诸塞州洛厄尔大学，并支持支付暑期培训计划上升初中学生在当地洛厄尔社区。 ResAx旨在为5，000多名服务不足的学生提供平等的高质量教育体验。该CAREER项目旨在开发体外牙龈组织系统，以研究微生物群落对人类口腔健康和疾病的作用，以及对牙周炎，特应性皮炎，哮喘和炎症性肠病等多种病理的潜在影响。除了代表庞大的人口和经济市场外，这些慢性病也是全球社会经济地位的新兴驱动因素。该CAREER项目的愿景将通过以下方式实现：（i）开发和验证微生理系统，以研究不同临床条件下的口腔宿主-病原体相互作用和微生物组学（ii）基于人原发性嗜中性粒细胞的发炎牙龈炎模型的工程化，以鉴定早期生态失调表现的临床指纹;和（iii）基于活化的B和T淋巴细胞和临床驱动的组织特征的牙周炎模型，以研究脂质介质对炎症消退的影响以及对已建立的多微生物群落的诱导变化。该奖项反映了NSF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进行评估，被认为值得支持审查标准。

The human body houses many different, but connected, microbial populations. For example, populations of tiny living things like bacteria, viruses and fungi, that can’t be seen with the naked eye. Some microbes make us sick while others are important for our health. Their balance or imbalance with each other and the surrounding tissues can exert long-lasting and wide-ranging effects on an individual’s state of health or disease. Of particular interest is the microbiota in the oral cavity, as it serves as a potential reservoir for pathogenic (disease causing) bacteria. However, very little is known about the relationship of various diseases and the oral microbiome. The research goal of this CAREER project is to understand the connection between the human oral tissue, the oral microbiome, and how they interact. This will be accomplished by creating an in vitro (in the lab) model of the human gingival (gum) tissue system capable of studying diverse microbial populations and their connection to overall human health. The goal of the project’s educational plan, called ResAx, is to provide a working model to address the drop in enrollment in low resources academic institutions that could be transposed to other research areas (i.e., medical devices, protein engineering). The multidisciplinary research project will provide opportunities to expand research access and education to undergraduate students enrolled in the BME curriculum at University of Massachusetts Lowell and to support a paid Summer Training Program for rising junior high school students in the local Lowell community. ResAx aims to provide equitable access to high-quality education experiences to more than 5,000 underserved students.This CAREER project targets the development of an in vitro gingival tissue system to study the role of microbial communities on human oral health and disease, with potential repercussion on diverse pathologies such as periodontitis, atopic dermatitis, asthma, and inflammatory bowel disease. In addition to representing a large population and economic market, these chronic diseases are emergent drivers of global socioeconomic status. The vision of this CAREER project will be accomplished by: (i) the development and validation of a microphysiological system to study oral host-pathogens interactions and microbiome biogeography under different clinical conditions (healthy, gingivitis and periodontitis); (ii) the engineering of an inflamed gingivitis model based on human primary neutrophils to identify a clinical fingerprint for early dysbiosis presentation; and (iii) a periodontitis model based on activated B and T lymphocytes and clinically driven tissue characteristics to investigate the effect of lipid mediators on inflammation resolution and induced changes on the established polymicrobial community.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.