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.

炎症性肠道疾病（IBD）影响了全球数百万个人，其发病率正在增加。这些疾病的特征是慢性复发和恢复胃肠道（GI）的感染，导致身体和社会心理症状使人衰弱。目前，众所周知，IBD是由宿主，微生物和环境因素之间的复杂相互作用导致的。尚不清楚的是这种复杂的相互作用如何触发该疾病，这会阻碍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，以开发一种可以安全地传递到GI区域以检测和治疗IBD的Theragnotic（治疗 +诊断）工具。热量工具的开发将使患有IBD的患者可以控制其症状，并过着更健康，更幸福的生活。此外，IBD热力将是概念验证，使能够开发能够治疗其他慢性疾病的更有可能的工具。除了提高IBD患者的生活质量外，该拟议的项目还制定了强大的教育计划，以发展多样性和具有全球竞争性的STEM劳动力。首先，来自STEM的人数不足的25名上升的7至9年级学生将参加“生物学夏令营的数据科学”。该营地的目的是激励参与者通过基于应用程序的学习来考虑STEM的职业。其次，该项目将通过有针对性的计划来增加本科生参与研究的参与，这将促使他们考虑STEM的高级学位。第三，该项目将培训明天的跨学科劳动力。拟议的研究将吸引一些最好的年轻人，为IBD建立热量工具。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，合成生物学和添加剂制造方面的基本培训，这将极大地使他们的未来职业受益。为了模拟宿主，微生物和环境因素之间的复杂相互作用，并开发了可以安全地传递到胃肠道的热工具，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，使用数据科学，研究小组将通过使用IBD多摩变数据库的数据来对复杂的宿主 - 微生物 - 环境相互作用进行建模，其中包含多个时间点的不同微生物集中概况的记录，以及饮食和吸烟习惯等环境因素的记录。该目标的成功完成将提供对IBD关键生物标志物的见解，以及疾病进展的机制，这些机制将纳入设计the theTagnostic工具。其次，使用合成生物学，研究小组将探索有关IBD关键生物标志物的信息，以构建工程细菌和感知IBD相关的炎症标记，并推动抗炎作用的表达。该目标的成功完成将导致热工程细菌，并针对炎症反应执行宿主校正的动作。第三，使用添加剂制造，研究团队将开发3D打印的智能药丸，以安全，安全地将theTagnotagnotic细菌送达给GI区的目标区域。该目标的成功完成将导致3D打印的智能药丸能够将工程细菌牢固地提供给GI块。最后，将评估数据科学，合成生物学和添加剂制造的协同整合，以确保IBD的TheTagnostic工具的成功设计。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛影响的审查标准来通过评估来获得支持的。