Comparative Physiology of Metabolism
I principally use two teleost research models, zebrafish (Danio rerio) and rainbow trout (Oncorhynchus mykiss) to comparatively study energy metabolism, using an integrated approach. This approach covers molecular, cellular and organismal aspects of energy metabolism, all of which integratively form the metabolic phenotype. A current research focus lies on the elucidation of epigenetic origins of metabolic phenotypes across ontogeny and generations, which in contrast to mammalian research models remains largely uncharacterized in lower vertebrates. In addition to providing comparative insight into epigenetic mechanisms governing the metabolic phenotype, the study of epigenetic mechanisms in fish models is especially applicable to three major areas addressed under this framework, which are outlined below.
In addition to being a valuable research model in the comparative physiology of metabolism, rainbow trout are the most important aquaculture species in Ontario. Following the recent sequencing of the rainbow trout genome, novel possibilities exist to address regulation and function of context-dependent epigenetic mechanisms in the metabolic phenotype. Focusing primarily on microRNAs, I am interested in how these molecular epigenetic mechanisms contribute to the metabolic phenotype in rainbow trout across ontogeny and at different levels of biological organization. In addition to providing insight into the evolution of microRNA mediated metabolic networks and function, the elucidation of these mechanisms will provide novel insight into the contribution of epigenetic mechanisms to rainbow trout specific phenotypes relevant to aquaculture. Examples include the implication of epigenetic mechanisms in mediating acute and sustained metabolic and growth effects of plant-based diets and the potential implication of epigenetic mechanisms in nutritional programming approaches.
Principally using the zebrafish model, Danio rerio, I am interested in the role of endocrine disrupting chemicals on the metabolic phenotype across ontogeny and generations either at baseline or in conjunction with environmental stressors experienced across ontogeny and generations. This represents an environmentally realistic scenario, as contaminants are subject to temporal variation due to regulation and continuing emergence of novel aquatic environments. A principal goal is to gain insight into germ-line dependent epigenetic mechanisms (principally DNA methylation) in the emergence of these phenotypes, and to develop epigenetic markers as improved prediction tools for EDC and aquatic contaminant exposure.
3) Teleost fish as models for metabolic disease
Zebrafish are increasingly used as model systems for disease including metabolic disease. Taking advantage of this model, a specific research interest lies in the elucidation of transgenerational interaction of non-exclusive biological hypothesis of metabolic disease. A principal aim is to gain understanding of the integration of the three major biological hypothesis across ontogeny and generations in the emergence of metabolic disease:
(1) The developmental origin of disease hypothesis ('Barker hypothesis')
(2) the contribution of environmental endocrine disrupting chemicals ('obesogen hypothesis')
(3) nutritional factors ('life-style hypothesis')
This approach is aimed to gain insight into novel epigenetic determinants and the identification of novel molecular drug targets for metabolic disease.