The principle unit of the circadian timing system is the cell. In mammals, nearly all cells have functional clocks that form a tightly controlled network of clocks. The suprachiasmatic nuclei (SCN) of the hypothalamus function receive environmental light input but also interact with other (peripheral) tissue clocks. While the SCN play a central role in the coordination of the circadian timing system, peripheral clocks have been shown to be essential for various tissue specific functions.
The work in my laboratory is focused on three topics:
Physiological clocks. Here, we mainly focus on central pacemaker. The SCN have a number of interesting network properties that we will address using novel in vivo microscopy techniques. Moreover, we are interested to further elucidate how do cellular clocks in different tissues interact with each other to generate the circadian timing system, which orchestrates physiology.
Pathological clocks and clock pathologies. What is the impact of disease on the clock, on the cellular and on the whole body level? Specifically, we are investigating the effect of cancerous transformation on the clock in cancer cells and the impact of chronic diseases like cancer on the function of the circadian timing system. Ultimately, this programme of work should also generate further evidence on the adaptive value of the circadian clock mechanism.
Chronotherapy. As part of the Warwick Chronotherapy Group (link to group webpage), we help to establish novel treatment schedules for cancer pharmacotherapy. Previously, it has been shown that timed dosing of cancer chemotherapy is beneficial for patients if their circadian timing system has been taken into account. Together with mathematical modelling of the underlying pharmacokinetic processes, we will address this issue for various standard chemotherapeutic drugs using in vitro and in vivo experimental models.
- Smith et al. 2022. Cell-type specific circadian bioluminescence rhythms recorded from Dbp reporter mice reveal circadian oscillator misalignment Journal of Biological Rhythms, DOI: 10.1177/07487304211069452Link opens in a new window.
- Jagannath et al. 2021. Adenosine integrates light and sleep signalling for the regulation of circadian timing in mice. Nature Communications DOI: 10.1038/s41467-021-22179-zLink opens in a new window.
- Okyar A, et al. 2019. Sex-, feeding-, and circadian time-dependency of P-glycoprotein expression and activity-implications for mechanistic pharmacokinetics modeling. Scientific Reports. DOI: 10.1038/s41598-019-46977-0Link opens in a new window.
- Schmitt, K., et al. 2018. Circadian control of DRP1 activity regulates mitochondrial dynamics and bioenergetics. Cell Metabolism. DOI: 10.1016/j.cmet.2018.01.011Link opens in a new window.