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）影响全球数百万人，其发病率正在增加。这些疾病的特点是慢性复发和缓解胃肠道炎症，导致虚弱的身体和社会心理症状。目前，已知IBD是宿主、微生物和环境因素复杂相互作用的结果。目前尚不清楚的是，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。该项目旨在模拟这种复杂的相互作用，以开发一种可以安全地输送到胃肠道的诊断（治疗+诊断）工具来检测和治疗IBD。这种诊断工具的开发将使IBD患者能够控制症状，过上更健康、更快乐的生活。此外，IBD诊断将是一个概念验证，能够开发出更多能够治疗其他慢性疾病的诊断工具。除了提高IBD患者的生活质量外，拟议的项目还具有强大的教育计划，以培养多元化和具有全球竞争力的STEM劳动力。首先，来自STEM领域代表性不足的社区的25名即将升入7 -9年级的学生将参加“生物数据科学夏令营”。训练营的目标是通过基于应用的学习激励参与者考虑从事STEM职业。其次，该项目将通过有针对性的项目来提高本科生对研究的参与度，这些项目将激励他们考虑攻读STEM的高级学位。第三，该项目将培养未来的跨学科劳动力。拟议中的研究将吸引一些最优秀的年轻人来建立IBD的诊断工具。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，这对他们未来的职业生涯非常有益。为了模拟宿主、微生物和环境因素之间复杂的相互作用，并开发一种可以安全输送到胃肠道的诊断工具，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，研究小组将利用IBD多组学数据库的数据对复杂的宿主-微生物-环境相互作用进行建模，该数据库包含几个时间点不同微生物集中的记录和环境因素，如几个受试者的饮食和吸烟习惯。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见解，这些将被纳入治疗诊断工具的设计。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，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细菌。这一目标的成功完成将导致诊断工程细菌能够执行针对炎症反应的宿主纠正作用。第三，利用增材制造技术，研究团队将开发一种3d打印的智能药丸，以安全安全地将诊断细菌输送到胃肠道的目标区域。这一目标的成功完成将导致3d打印智能药丸能够将工程细菌安全有效地输送到胃肠道。最后，将评估数据科学、合成生物学和增材制造的协同集成，以确保IBD诊断工具的成功设计。该奖项反映了美国国家科学基金会的法定使命，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.