The role of environmental organohalogenated contaminants on lipid metabolism and biological action

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We are continuously exposed to environmental contaminants from their presence in our diet and environment. These contaminants are known to manipulate fundamental biological pathways regulated by genes and proteins. However, complete understanding of contaminant fate is lacking because of uncertainty regarding their interaction with lipid signaling molecules. Signaling lipids have long been recognized as vital to an organism's biological processes. My proposed research aims to elucidate the relationship between a class of emerging contaminants, the fluorinated substances, and signaling lipids, to fully appreciate how basic and higher-order cell functions respond and adapt to this exposure. Results gained will enable us to better predict biological outcome after environmental contaminant exposure. Research by myself and others has shown that fluorinated substances induce enzymes, modify proteins, and bind to receptors. I hypothesize these processes to be linked to signaling lipid activity. Using cell and animal models routinely used to study protein signaling and patterns of gene regulation, we can measure and place signaling lipids in context with these traditionally studied pathways. We will employ genetic (validation of genes), biochemical (characterizing proteins), and chemical (substances that activate specific targets) approaches to delineate how lipids are affected after contaminant exposure in numerous processes. We will identify specific lipids formed in response to fluorinated substance exposure and enzyme induction. Then, we will examine basic cell stress and defense pathways employed after proteins are modified by fluorinated substances. This program will also explore how receptor binding induces angiogenesis, a fundamental process involved in wound healing and development, which depends on the action of several signaling lipids. The bioanalytical methods used to analyze these lipids are unique to a small number of laboratories worldwide. These methods will be instrumental to my program, and novel to the Canadian scientific community. This program addresses critical areas of uncertainty in fields of environmental chemistry and biology. The research will advance knowledge of biological processes affected by environmental contaminants by understanding the ways that signaling lipids act in concert with other pathways to combat cellular insult and maintain function. The program will result in the training of students in fields of environmental chemistry, biochemistry, and molecular biology. Students will develop critical thinking and scientific expertise, complemented by strong communication and leadership skills. Results will be documented in specialized open access journals of bioactive chemicals and lipid biochemistry, as well as broad interest journals of environmental chemistry and biology.