Hjelt grant holder 2015, University of Geneva
The molecular mechanisms of the circadian clockwork and their roles in metabolism regulation and the etiology of diseases such as diabetes and cancer
New insights into the circadian clock and type 2 diabetes. Charna Dibner is the head of a recently established research group in the Division of Endocrinology, Diabetes, Hypertension and Nutrition, Geneva University Hospital and recipient of a grant of CHF 50,000 from the Hjelt Foundation. Charna Dibner undertook her PhD in the field of neurological development, and her postdoc in the field of mammalian circadian clocks. The circadian clockwork is a biochemical mechanism that oscillates with a period of exactly 24 hours when it receives daily corrective signals from the environment, primarily daylight and darkness.
“I came across papers on the circadian clock by Professor Ueli Schibler, my postdoctoral supervisor, and found the subject captivating. It’s quite amazing how universal this mechanism is. It has become increasingly clear that the circadian clock is functional in nearly every cell, and impacts critically on most aspects of physiology and behaviour,” she says.
The role in metabolism
Charna Dibner’s laboratory investigates the molecular mechanisms of the circadian clockwork and their roles in metabolism regulation and the etiology of diseases such as diabetes and cancer. This is a recent subject not even a decade old. What is quite intuitive in the discovery of the connection between the clock and metabolism is that certain bodily tasks should not occur at the same time. During catabolic and anabolic processes, such as eating, for example, we need to digest food and then store any unused energy within the body; this should not happen simultaneously. One of the obvious functions of the clock is temporarily segregating opposite metabolic processes to make our body more economical.
“Our long-term goal is to clarify the relationship between the circadian clock and metabolism and its effect on physiological conditions, and on obesity and type 2 diabetes. We are also focusing on the relationship between the circadian clock and cancer progression,” Charna Dibner says.
Most, if not all, metabolic processes are subject to diurnal oscillations and, conversely, daily feeding-fasting rhythms are the dominant timing cues in the synchronisation of circadian clocks in peripheral organs. The disruption of circadian physiology imposed by social constraints on many human subjects, such as the chronic ‘social jetlag’ phenomenon, can have severe consequences on their health conditions. Concomitant with increasing sleep deficit and irregular mealtimes, there is a worldwide rise in the incidence of metabolic disorders and type 2 diabetes, and both biological and epidemiological studies suggest a direct link between lifestyle and these metabolic disorders.
However, the genetic and biochemical connections between circadian clocks and metabolic disorders are still poorly understood in humans. It is therefore of utmost scientific and clinical importance to provide further insights into the emerging connection between the circadian oscillator function and the etiology of obesity and type 2 diabetes. If we succeed in establishing a molecular link between the circadian clock and these metabolic disorders, modulating the oscillator could be considered to be a new potential therapeutic avenue.