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

合作研究：SCH：炎症性肠病的治疗和诊断系统：整合数据科学、合成生物学和增材制造

• 批准号: 2306740
• 负责人: Bo Wang
• 金额: $ 16.87万
• 依托单位: Florida Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2027-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2306740&HistoricalAwards=false
• 关键词: Collaborative; Research; SCH; Therapeutic; Diagnostic

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.

炎症性肠病(IBD)在全球范围内影响着数百万人，其发病率正在上升。这些疾病的特点是胃肠道(GI)慢性复发和缓解性炎症，导致虚弱的身体和心理社会症状。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。目前尚不清楚这种复杂的相互作用是如何触发这种疾病的，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，开发一种可以安全地输送到胃肠道以检测和治疗IBD的诊断(治疗+诊断)工具。诊断工具的开发将使IBD患者能够控制自己的症状，过上更健康、更幸福的生活。此外，IBD诊断将是一种概念验证，能够开发出更多能够治疗其他慢性病的诊断工具。除了提高IBD患者的生活质量外，拟议的项目还有一个强有力的教育计划，以培养一支多元化和具有全球竞争力的STEM劳动力。首先，25名来自STEM代表性不足的社区的7-9年级新生将参加“生物数据科学夏令营”。夏令营的目标是通过基于应用的学习，激励参与者考虑在STEM工作。其次，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攻读STEM高级学位。第三，该项目将培训明天的跨学科劳动力。这项拟议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，参与该项目的研究生将接受数据科学、合成生物学和添加剂制造方面的基础培训，这些培训将对他们未来的职业生涯大有裨益。为了模拟宿主、微生物和环境因素之间的复杂相互作用，并开发可以安全地输送到GI区域的诊断工具，该项目通过三个主要目标整合了数据科学、合成生物学和添加剂制造。首先，研究团队将利用数据科学，通过使用IBD多组学数据库的数据来模拟复杂的宿主-微生物-环境相互作用，该数据库包含几个时间点不同微生物重点图谱的记录，以及几个受试者的环境因素，如饮食和吸烟习惯。这一目标的成功完成将提供对IBD关键生物标志物的洞察，以及疾病进展的机制，这些将被纳入到设计诊断工具中。其次，利用合成生物学，研究小组将利用IBD关键生物标记物的信息来构建一种能够感知IBD相关炎症标记物并驱动抗炎效应分子表达的工程菌。这一目标的成功完成将导致一种能够对炎症反应执行宿主纠正行动的基因工程细菌。第三，利用添加剂制造，研究团队将开发一种3D打印的智能药丸，以安全可靠地将不可知性细菌输送到胃肠道的目标区域。这一目标的成功完成将产生一种3D打印的智能药丸，能够将工程菌安全有效地输送到胃肠道。最后，将对数据科学、合成生物学和添加剂制造的协同集成进行评估，以确保成功设计用于IBD的诊断工具。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。