My laboratory is interested in the neurological and endocrine systems that govern energy balance (food intake, metabolism, body weight and body composition). We have a particular interest in the role played by the circadian clock in strengthening homeostatic controls, and how clock disruption may contribute to the development and severity of metabolic disease (obesity, diabetes, cardiovascular disease).
Feeding behaviour (i.e., what, when, and how much we eat) is a complex process incorporating instinctual and homeostatic drives (which ensure adequate energy supply) and hedonistic and reward pathways (which reinforce pleasurable aspects of food intake), as well as higher cognitive mechanisms (which provide contextual and learned information). Nonetheless, for most people, body weight and body composition remain relatively static throughout adult life. This is because regulatory centres within the brain are generally very good at balancing food intake with energy need and/or expenditure. In its simplest form, this regulatory (homeostatic) control is dictated by the relative activity of orexigenic (promoting food intake) and anorexigenic (inhibiting food intake) neurons within an area of the brain called the hypothalamus. These cells respond to fluctuations in circulating nutrient (e.g., glucose, fatty acids, amino acids) and hormone (e.g., leptin, ghrelin, insulin) levels that reflect our energy status or needs, to elicit the appropriate responses (i.e. appetite, hunger, satiety). Unfortunately, in some circumstances homeostatic controls become profoundly overwhelmed resulting in chronic disruption of energy balance (e.g. obesity) and potentially severe eating and metabolic disorders (e.g. anorexia nervosa and cachexia).
Much of our physiology and behaviour is patterned across the 24hr day. Coordination of these patterns (circadian rhythms) is driven by an internal biological clock system that runs within the brain, as well as most tissues of the body. It is now clear that the circadian clock is also critical in our ability to maintain a normal energy balance. By modulating the activity of feeding centres in the hypothalamus, modulating reward pathways, and gating the production and release of energy-related signals and hormones, all influenced by time of day, the circadian clock has a profound influence over feeding behaviour and metabolism. It is also becoming clear that disruption of our bodies’ natural rhythms increases the incidence and severity of neurological and metabolic diseases.
Our research examines how and where the circadian system intersects with metabolic and feeding controls to exert this influence. For example, recent work within the lab has identified components of the molecular clock, which act as a critical modifier of food intake, influencing not only the timing of feeding but also amount and diet preference. It is our hope that such studies will identify novel avenues for therapeutic intervention for a range of neurological, metabolic and eating disorders. Our research is founded on an integrative approach, which spans from molecular biology to whole animal physiology. We employ innovative models and techniques including novel transgenics, comprehensive physiological monitoring and in vivo imaging to explore circadian and metabolic function.