Untargeted Identification of Priority Environmental Chemicals and Their Physical Protein Targets

在过去几十年中，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全世界某些疾病发病率增加之间的联系的关注。然而，由于环境基质是数千种已知和未知化学品的极其复杂的混合物，因此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。事实上，目前常规监测的化学品只是以一种公正的方式进行解释，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学研究方面的专家来支持我们的追求。具体而言，将开发非靶向化学分析方法，以对环境混合物中的化学物质进行无偏鉴定；然后，这些已确定的化学品将根据其持久性、生物蓄积性和毒性进行优先处理；同时，将建立一个化学蛋白质组学平台，用于蛋白质组范围内的蛋白质靶点鉴定和优先化学物质的毒性机制。

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.