Diet and the epigenome: Investigating the impact of the environment on cell biology

点击翻译按钮获取中文摘要

Human cell functioning is determined by the genetic code as well as non-genetic factors called epigenetics that include enzymes found in the human body. Human DNA, a molecule that stores genetic information, undergoes specific epigenetic modifications. Epigenetics influences cellular functions without changing the underlying genetic code. The epigenetic modifications are dynamic and susceptible to changes upon various internal and external factors (e.g., malnutrition, aging, sedentary lifestyle, hormonal imbalance, toxins, pollutions, excessive alcohol and sun exposure). Aberrant epigenetic patterns have been extensively studied in different disorders with focus on prevention, detection and treatment. For instance, a number of studies, including our work, provide evidence that dietary bioactive compounds can act to reverse aberrant epigenetic patterns and modulate the disease state and disease risk. However, most epigenetic studies have largely ignored the role of the environment (e.g., dietary bioactives) on normal cell biology. Importantly, our recent work argues that the environment plays a role in regulation of cell biology through epigenetics. The long-term vision of my Discovery research program is to study how the environment (e.g., diet) impacts cell biology through epigenetic mechanisms. In the next five years, my short-term goals will focus on the functional roles of epigenetic enzymes and chromatin-modifying proteins in effects on cell biology exerted by two dietary polyphenols from phytoestrogens, that have distinct chemical structures. Studying phytoestrogens' impact on cell biology is especially important from a toxicology point of view. Namely, numerous environmental contaminants, including bisphenol, nonylphenols, parabens, and phthalates, have estrogen-like effects and are potent endocrine disruptors, which impact human, animal and plant life. Findings generated through the proposed NSERC Discovery research program will propose mechanisms that could well be involved in the action of other environmental estrogens. Significance: Studies described in the proposed NSERC Discovery research program will explore how epigenetic mechanisms mediate the impact of the environment on cell biology. This will further our understanding of the connection between epigenetic regulation of gene transcription and the phenotype in response to environmental cues (e.g., diet). Taking into account that nearly all biological processes have an epigenetically regulated component, our findings will broadly impact numerous disciplines in natural sciences, including chemistry and biology. Lastly, the proposed program will enable highly qualified personnel in my laboratory to develop new high-level skills in genomics, epigenomics, gene editing, and computational analyses which will make them highly competitive in future employment.