PFI-TT: Development of a C. elegans-based Technology to Enhance the Drug Discovery Process and to Predict Preclinical Efficiency

PFI项目更广泛的影响/商业潜力在于其加速和提高制药行业开发新治疗药物效率的潜力。这项技术不仅具有巨大的商业潜力，而且有助于解决美国公众尚未解决的健康挑战。考虑到开发新药所需的时间和资源，我们的技术有可能成为该行业的主要工具，同时刺激经济活动。反过来，这个项目可以间接地帮助推进对衰弱性疾病的治疗，从而改善美国人民的健康和福利。此外，该项目将为学生提供一个独特的机会，不仅可以获得超出正常研究活动的创新经验，还可以获得指导和培训，帮助他们在毕业后进入劳动力市场。因此，他们在追求这个领域的职业生涯时可能更具竞争力。拟议的项目旨在提高临床前药物发现过程的效率，这是制药行业尚未满足的主要需求。该项目的目的是验证一种利用秀丽隐杆线虫作为中间系统的技术，在药物发现过程的早期阶段降低化合物的风险。该技术将一种潜在的治疗药物暴露于蠕虫体内引发的应激反应中，并评估其缓解应激反应的能力，以此作为其治疗潜力的代表。我们将采用包括显微镜、遗传学和药理学在内的综合方法来充分开发这项技术。该项目包括3个里程碑。里程碑1的目标是通过在模拟工业环境的环境中进行测试来验证该技术。里程碑2的目标是开发完全自动化的技术。里程碑3的目标是建立测试化合物与其生物靶点之间的机制联系。如果成功，该项目可能会为药物发现提供重要的功效增强。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。

The Broader Impact/commercial potential of the PFI project resides in its potential to both expedite and increase the efficiency of developing new therapeutic drugs by the pharmaceutical industry. This technology not only holds immense commercial potential but also serves to help address unmet health challenges of the American public. Given the time and resources needed to develop new drugs, our technology has the potential to become a major tool for the industry while stimulating economic activity. In turn, this project can indirectly help advance the treatment for debilitating medical conditions and thus improve the health and welfare of the American people. In addition, this project will provide an unique opportunity for the students to not only gain innovation experience beyond their normal research activities but further, to receive guidance and training to help them enter the workforce upon graduation. Thus they may be more competitive in their pursuit of careers in this space.The proposed project is aimed at enhancing the efficiency of the preclinical drug discovery process which is a major unmet need of the pharmaceutical industry. The objective of this project is to validate a technology utilizing C. elegans worms as an intermediary system to de-risk compounds during the early phases of the drug discovery process. The technology exposes a potential therapeutic drug to stress responses that are elicited in the worm and evaluates its ability to mitigate them as a proxy of its therapeutic potential. We will use an integrated approach that includes microscopy, genetics, and pharmacology to fully develop the technology. The project encompasses 3 milestones. The goal of Milestone 1 is to validate the technology by testing it in an environment that mimics an industrial setting. The goal of milestone 2 is to develop the technology to become fully automated. The goal of Milestone 3 is to establish mechanistic links between the test compounds and their biological targets. If successful, this project may provide a major efficacy enhancement in drug discovery.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.