Untargeted Identification of Priority Environmental Chemicals and Their Physical Protein Targets

过去几十年来，环境科学取得了令人印象深刻的发展，这引起了人们对环境污染与加拿大和世界范围内某些疾病发病率不断上升之间的联系的关注。然而，对环境化学品的健康风险进行预防性评估仍有许多不足之处，因为环境矩阵是数千种已知和未知化学品的令人难以置信的复杂混合物。事实上，目前常规监测的化学品只是以不偏不倚的方式进行解释，然后利用这些知识来改善环境化学品管理。我们将通过成为非靶向化学分析和环境化学蛋白质组研究方面的专家来支持我们的追求。具体地说，将开发无针对性的化学分析方法，无偏见地识别环境混合物中的化学物质；然后根据持久性、生物累积性和毒性对这些已识别的化学物质进行优先排序；同时，将建立化学蛋白质组学平台，用于在蛋白质组范围内识别优先化学物质的蛋白质靶标和毒性机制。 值得注意的是，拟议的研究计划将提供一个前所未有的机会，以公正的方式评估环境化学品的健康风险。这将加强目前对环境污染与加拿大一些疾病发病率上升之间的联系的认识。除了社会效益和环境效益外，拟议研究产生的技术还将为环境科学和制药业带来直接经济效益。 重要的是，拟议的研究计划的成果不仅仅是公布的发现，它还将为学生提供高级培训机会。在接下来的五年里，我的团队预计将发展到大约7名研究生和2名博士后研究员。作为一名新的独立研究员，我已经开始培训三名学生和两名博士后研究员。我在招聘中的早期成功源于我们的创新研究计划，以及学生追求研究目标的热情，并学习对他们未来独立职业发展至关重要的技术技能(如质谱学、蛋白质组学)和更广泛的能力(如沟通、领导力)。

Impressive developments in environmental science over the past decades have raised the concern about the links between environmental pollution and increasing incidence of some diseases in Canada and worldwide. However, preventative assessment of the health risks of environmental chemicals leaves much to be desired since environmental matrices are incredibly complex mixtures of thousands of known and unknown chemicals. In fact, current routinely monitored chemicals only explain in an unbiased fashion, and then exploit this knowledge for improved environmental chemical management. We will support our pursuit by becoming experts in untargeted chemical analysis, and environmental chemical proteomics research. Specifically, untargeted chemical analysis methods will be developed for unbiased identification of chemicals in environmental mixtures; then these identified chemicals will be prioritized according to their persistence, bioaccumulation and toxicities; concurrently, a chemical proteomics platform will be established for proteome-wide identification of protein targets and toxic mechanisms of priority chemicals. Notably, the proposed research program will provide an unprecedented opportunity to assess the health risks of environmental chemicals in an unbiased fashion. This will strengthen current knowledge of links between environmental pollution and increasing incidence of some diseases in Canada. In addition to the societal and environmental benefits, the techniques generated from the proposed research will also lead to direct economic benefits to environmental science and the pharmaceutical industry. Importantly, the outcome of the proposed research program is more than published discoveries, it will also provide advanced training opportunities to students. Over the next five years, my group is expected to grow to approximately 7 graduate students and 2 postdoctoral fellows. Already as a new independent researcher, I have begun training of three students and two postdoctoral fellows. My early success in recruitment stems from our innovative research program, as well as students' enthusiasm to pursue their research goals, and learn technical skills (e.g. mass spectrometry, proteomics) and broader abilities (e.g. communication, leadership) that are critical to develop their future independent careers.