Grant: Discovery Grants Program - Individual

Oxygen radicals, also known as reactive oxygen species (ROS), are unfortunate by-products that arise both internally from regular cell metabolism and externally from our environment. As one ages, there is a cumulative damage to cells, proteins (resulting in protein unfolding), and DNA due to these reactive oxygen species. Evolution has given rise to cellular pathways designed to mitigate the damage from ROS and unfolded proteins. These pathways act by expressing enzymes that neutralize them, thus limiting the long-term damage to the organism. As my research program addresses questions in basic cell biology, it does not encompass Indigenous communities, societies, or individuals. As a result, it does not meet the criteria for Indigenous research as defined by NSERC. We aim to examine these protective pathways genetically, using C. elegans as our model organism that regulates the production of antioxidant proteins. This worm has been invaluable in genetic research due to its ease of cultivation, its size which allows for the characterization of every individual cell in the organism (with approximately 1000 total cells), and our ability to manipulate its genes either by insertion of modified genes or by creating specific mutations. Many genes in humans, especially those pivotal in biological processes like protection against ROS, also exist in C. elegans. In our prior research where we did a genetic suppression screen with C. elegans, we identified the potential significance of three candidate proteins in the oxidative stress response: NHR-37, NHR-14, and ZTF-22. These proteins might act as crucial gene regulators in the context of oxidative stress within cells. This proposal focuses on using C. elegans to delve deeper into the roles these proteins play in regulating the oxidative stress response. We'll do this by studying genetic mutants that suppress the production of these proteins. We aim to determine if NHR-37, NHR-14, and ZTF-22 play a beneficial role in producing antioxidant proteins and in reducing the damage caused by oxygen radicals when required. Furthermore, we seek to uncover the exact mechanisms by which these proteins function in the oxidative stress response. Another stress response pathway we're keen to explore is the unfolded protein response. We hypothesize that a protein we previously studied, BRAP-2, has a regulatory role in this stress response. Our investigations will extend to understanding the interplay between the oxidative stress response and the unfolded protein response. Ultimately, the programmatic goal of my research is to enhance our understanding of how animal cells manage the damage inflicted by harmful entities like oxygen radicals.