metrology of bioactive molecule and target discovery

生物活性分子计量和靶标发现

• 批准号: CRC-2021-00160
• 负责人: Beaudry, Francis
• 金额: $ 14.57万
• 依托单位: Université de Montréal
• 依托单位国家: 加拿大
• 项目类别: Canada Research Chairs
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=746059
• 关键词: metrology; bioactive; molecule; target; discovery

There is a critical unmet medical need to treat human and animal patients suffering from chronic pain leading to functional impairment. Animal health, welfare and pain management is at the heart of our mission in veterinary medicine. Developing new therapeutics for pain management is a challenge because it requires the use of experimental animal models, where we induce pain. There are numerous limitations, including ethical considerations, technical challenges and cost. Therefore, it is imperative to develop new strategies leading to a paradigm shift in how we develop new therapeutics to alleviate pain. Molecular fingerprinting for precision therapies is the heart of precision medicine. This new paradigm is a departure from the "one-size-fits-all" traditional approach and prioritizes patient characteristics (i.e. molecular and phenotypic). Specifically, a comprehensive molecular profiling using proteomic technologies of characterized patients can be used to develop targeted and more specific pain therapies to improve clinical outcomes in veterinary patients and improve the translation of analgesic drugs to the clinic. This is a tremendous opportunity to make remarkable advancements in knowledge, since naturally occurring disease studies in animals have more translational value to other animal species and humans. The Canada research chair in metrology of bioactive molecule and target discovery mission will be to methodically characterize the molecular signature of veterinary patients suffering from chronic pain and identify new bioactive molecules and their targets to design innovative pain relief strategies to improve animal welfare and strengthen the translation of analgesic drugs to the clinic. The Research Chair will have three axes: 1) Perform comprehensive characterizations of the molecular signatures that underlie chronic and inflammatory pain; 2) Develop innovative mass spectrometry analytical strategies with increased detection sensitivity to precisely study protein target engagement and identify new bioactive molecules and new targets; 3) Develop and validate alternatives and high-throughput methods to evaluate the efficacy of drug candidates using Caenorhabditis elegans to meet ethical objectives and broaden the number of candidates tested. We strive to develop innovative solutions to resolve unmet needs in the drug treatment of chronic pain.

治疗患有导致功能障碍的慢性疼痛的人类和动物患者存在严重的未满足的医疗需求。动物健康、福利和疼痛管理是我们兽医使命的核心。开发用于疼痛管理的新疗法是一项挑战，因为它需要使用实验动物模型，在那里我们诱导疼痛。有许多限制，包括道德考虑、技术挑战和成本。因此，必须制定新的策略，从而在我们如何开发新的治疗方法来减轻疼痛方面实现范式转变。 精准治疗的分子指纹是精准医学的核心。这种新的模式是从“一刀切”的传统方法和患者的特点（即分子和表型）的优先顺序出发。具体而言，使用蛋白质组学技术对特征化患者进行全面的分子分析，可用于开发靶向和更特异性的疼痛疗法，以改善兽医患者的临床结局，并改善镇痛药物向临床的转化。这是一个巨大的机会，使知识的显着进步，因为在动物中自然发生的疾病研究有更多的转化价值，以其他动物物种和人类。加拿大生物活性分子计量学研究主席和目标发现使命将是系统地表征患有慢性疼痛的兽医患者的分子特征，并确定新的生物活性分子及其目标，以设计创新的疼痛缓解策略，以改善动物福利并加强镇痛药物的临床转化。 研究主席将有三个轴：1）进行慢性和炎症疼痛的分子特征的全面表征; 2）开发具有更高检测灵敏度的创新质谱分析策略，以精确研究蛋白质靶点接合并识别新的生物活性分子和新靶点; 3）开发和验证替代品和高通量方法，以评估使用秀丽隐杆线虫的候选药物的疗效，以满足伦理目标并扩大测试的候选药物数量。我们致力于开发创新的解决方案，以解决慢性疼痛药物治疗中未满足的需求。