Mechanisms of coping with a lifetime of environmental challenges: Integrating growth, metabolism and stress physiology across multiple generations

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Aquatic environments are constantly challenged by temperature shifts, pharmaceuticals and pesticides. We are just starting to understand how these stressors impact animal physiology over short and long-term. Most studies to date focus on either early life stage exposure to the stressors or on acute exposure of adults. Few focus on lifecycle exposure and how it impacts physiology and even fewer explore whether the effects are transmitted across multiple generations. The long-term vision of my research program is to understand how integrated responses at the growth, metabolism and stress axes, predict how aquatic organisms respond to complex challenges over their lifetime. I will explore how challenges impact mitochondria functioning and energy utilization, and whether these effects are multi- or transgenerational. A first short-term goals of my work will focus on exploring how these systems are impacted by the pharmaceutical metformin (Met) and the pesticide niclosamide (Nic) following a lifetime of exposure, from fertilization to adulthood, since both impair mitochondrial function and energy metabolism. A second goal will focus on exploring whether the exposures have multigenerational effects, via the maternal or paternal lines, using zebrafish as model organisms. To this end, animals will be exposed to Met and Nic from fertilization to adult stages. Tissues will be collected and solid-phase extraction protocols will be developed to measure the chemicals in fish tissues using liquid chromatography-time-of-flight-mass spectrometry. HQP will conduct tissue processing for endpoint and kinetic assays to measure tissue metabolic capacity, energy reserves and will perform mitochondria isolations to determine how life-cycle exposure impacts function at various developmental stages. These endpoints will be explored in the context of male vs female effects, to investigate sex-specific differences in responses. To investigate the effects of Nic and Met on the animals, from genes to whole organism, we will perform real-time quantitative PCR, ELISAs, steroid hormone measurements and oxygen consumption assays in fish. Next, these parameters will be measured in subsequent generations, by doing paired crosses with exposed and non-exposed parental lineages. This program will provide HQP with an integrative, interdisciplinary and hands-on experience, working on an environmentally relevant project. HQP will gain molecular and analytical chemistry skills, will be able to conduct biochemical assays and organelle isolation techniques, all of which are relevant to the fields of environmental physiology, pharmacology and toxicology. This work will improve our understanding of how fish respond to a lifetime of stress and will allow us to better predict population-level effects. HQP will be trained in transferable skills, such as bias awareness, multiple ways of knowing, gender bias in sciences and will be introduced to environmental research in Canada.