Collaborative Research: SCH: Therapeutic and Diagnostic System for Inflammatory Bowel Diseases: Integrating Data Science, Synthetic Biology, and Additive Manufacturing

炎症性肠病（IBD）影响全世界数百万人，并且其发病率正在增加。这些疾病的特征在于胃肠道（GI）的慢性复发性和缓解性炎症，导致使人衰弱的身体和心理社会症状。目前，已知IBD由宿主、微生物和环境因素之间的复杂相互作用引起。目前尚不清楚这种复杂的相互作用是如何引发这种疾病的，这阻碍了准确的诊断和有效治疗的发展。该项目旨在对这种复杂的相互作用进行建模，以开发一种治疗（治疗+诊断）工具，可以安全地输送到胃肠道以检测和治疗IBD。治疗诊断工具的开发将使IBD患者能够控制他们的症状，过上更健康，更快乐的生活。此外，IBD治疗不确定性将是一个概念验证，能够开发更多能够治疗其他慢性疾病的治疗不确定性工具。除了改善IBD患者的生活质量外，拟议的项目还有一个强有力的教育计划，以培养多元化和具有全球竞争力的STEM劳动力。首先，来自STEM代表性不足的社区的25名7 - 9年级学生将参加“生物学数据科学夏令营”。夏令营的目标是激励参与者通过基于应用的学习考虑STEM职业。第二，该项目将通过有针对性的计划增加本科生对研究的参与，这些计划将激励他们考虑STEM的高级学位。第三，该项目将培养未来的跨学科劳动力。这项拟议中的研究将吸引一些最优秀的年轻人来为IBD建立一个治疗不可知论工具。由于拟议研究的高度跨学科性质，参与该计划的研究生将接受数据科学，合成生物学和增材制造方面的基础培训，这将极大地有利于他们未来的职业生涯。为了模拟宿主、微生物和环境因素之间的复杂相互作用，并开发一种可以安全地输送到胃肠道的治疗诊断工具，该项目通过三个主要目标整合了数据科学、合成生物学和增材制造。首先，利用数据科学，研究小组将通过使用IBD多组学数据库中的数据来模拟复杂的宿主-微生物-环境相互作用，这些数据库包含几个时间点不同微生物集中分布的记录以及几个受试者的饮食和吸烟习惯等环境因素。这一目标的成功完成将为IBD的关键生物标志物以及疾病进展机制提供深入见解，这些将被纳入治疗诊断工具的设计中。其次，利用合成生物学，研究小组将利用IBD关键生物标志物的信息来构建一种能够感知IBD相关炎症标志物并驱动抗炎效应物表达的工程菌。这一目标的成功完成将导致治疗不确定性工程菌能够对炎症反应进行宿主校正作用。第三，利用增材制造，研究小组将开发一种3D打印的智能药丸，以安全可靠地将治疗诊断细菌运送到胃肠道的目标区域。这一目标的成功完成将导致3D打印的智能药丸能够安全有效地将工程细菌输送到胃肠道。最后，将对数据科学、合成生物学和增材制造的协同整合进行评估，以确保IBD治疗诊断工具的成功设计。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审查标准进行评估，被认为值得支持。

Inflammatory bowel diseases (IBD) affect several million individuals worldwide, and their incidence is increasing. These diseases are characterized by chronic relapsing and remitting inflammation of the gastrointestinal (GI) tract, resulting in debilitating physical and psychosocial symptoms. Currently, it is known that IBD results from a complex interplay among host, microbial, and environmental factors. What is not known is how this complex interplay triggers the disease, which impedes an accurate diagnosis, and the development of efficient treatments. This project aims at modeling this complex interplay, to develop a theragnostic (therapeutic + diagnostic) tool that can be safely delivered to the GI tract to detect and treat IBD. The development of the theragnostic tool will allow patients with IBD to control their symptoms and live a healthier and happier life. Furthermore, the IBD theragnostic would be a proof-of-concept enabling the development of more theragnostic tools capable of treating other chronic diseases. Besides improving the quality of life of IBD patients, the proposed project has a strong educational plan to develop a diverse and globally competitive STEM workforce. First, 25 rising 7th-9th-grade students from communities underrepresented in STEM will participate in the “Data Science in Biology Summer Camp”. The goal of the camp is to motivate participants to consider a career in STEM through application-based learning. Second, the project will increase the participation of undergraduate students in research through targeted programs that will motivate them to consider an advanced degree in STEM. Third, the project will train the interdisciplinary workforce of tomorrow. The proposed research will attract some of the best young minds to build a theragnostic tool for IBD. Due to the highly interdisciplinary nature of the proposed research, graduate students involved in this program will receive fundamental training in data science, synthetic biology, and additive manufacturing which will highly benefit their future careers. To model the complex interplay among host, microbial and environmental factors, and develop a theragnostic tool that can be safely delivered to the GI tract, the project integrates data science, synthetic biology, and additive manufacturing through three main objectives. First, using data science, the research team will model the complex host-microbes-environment interplay by using data from the IBD Multi-omics Database, containing records of different microbially focused profiles at several points in time and environmental factors such as dietary and smoking habits for several subjects. The successful completion of this objective will provide insights into critical biomarkers of IBD, as well as the mechanisms of disease progression, which will be incorporated to design the theragnostic tool. Second, using synthetic biology, the research team will exploit the information on key biomarkers of IBD to build an engineered bacteria able to sense IBD-associated inflammatory markers and drive the expression of anti-inflammatory effectors. The successful completion of this objective will result in a theragnostic engineered bacteria able to perform host-correcting actions against inflammatory responses. Third, using additive manufacturing, the research team will develop a 3D-printed smart pill to securely and safely deliver the theragnostic bacteria to target regions of the GI tract. The successful completion of this objective will result in a 3D-printed smart pill able to deliver the engineered bacteria securely and effectively to the GI tract. Finally, the synergistic integration of data science, synthetic biology, and additive manufacturing will be evaluated to guarantee the successful design of a theragnostic tool for IBD.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.