Frederic Gachon

Specific role of the circadian clocks in the different liver cell types and how they interact

The goal of this project is to define the specific role of the circadian clock in the different cell types of the liver (hepatocytes, stellate cells, endothelial cells...) and how the perturbation of these cell-specific circadian clock is involved in liver pathologies. This project will involve genetically modified animal models, RNA-sequencing, protein analysis and evaluation of metabolic parameters.

Regulation of liver protein secretion and its regulation by circadian and feeding rhythms

While most of blood proteins are secreted by the liver, how they are secreted is still not clear, as well as the regulation of this secretion. Our previous experiments showed that liver protein secretion is rhythmic and regulated by feeding rhythms in both mouse and human. Using newly generated animal model and experiments in cultured cells, this project will decipher the mechanisms involved and the consequences of the perturbation of this rhythmic secretion on animal physiology.

Improving the recovery of ICU patients through the preservation of their circadian physiology

The ICU of the Future project is a TPCH Critical Care Research Group project, employing a collaborative multi-disciplinary and intersectoral approach, putting patients at the centre of ICU design. The purpose is to fundamentally redesign the ICU environment to not only achieve survival, but provide a superior recovery experience, optimised outcomes of care and quality of life beyond, incorporating the patient’s needs and wishes into an improved ICU design. The project team is working with ICUs across Metro North, but also partnering with other ICUs across the state and nationally. The project team, comprising clinicians and researchers (including nursing, allied health, psychology, psychiatry and intensive care specialists), have worked closely with patients and world leading industry partners such as Philips, Getinge, Ascom and Lendlease, to reconceptualise intensive care, co-designing an ultra-modern recovery focussed ICU bedspace. Using advanced technology and evidence-based design, the proposed new bedspace tailors the care environment to patient’s shifting clinical needs and personal preferences.

The adverse impact of critical illness and an ICU admission on patients’ circadian rhythms are well known. The sleep deprivation experienced by patients spending prolonged periods in an ICU and the loss of their normal circadian rhythms have been documented in multiple studies. However, there is scant information about the impact of the physical and sensory environment on patients circadian rhythms, and we are not aware of any studies investigating how a modified / improved ICU bedspace environment impacts on patients circadian rhythms. Similarly, there is limited information available about the longer term impact this loss of circadian rhythm has on patients, and whether it impacts on their ability to recover physically, cognitively and/or psychologically.

This PhD project is a part of the larger ICU of the Future project. It is a collaborative project with the UQ IMB, aiming to analyse how the ICU environment impacts on patients’ circadian rhythms and how an improved environment impacts the circadian rhythms of patients during their ICU admission, and how this affects the recovery of their physical, cognitive and mental health.

Circadian regulation of protein glycosylation

Protein glycosylation plays an important role in protein maturation, trafficking and secretion. Our recent evidences suggest that glycosylation and synthesis of gangliosides could be a rhythmic process regulated by the circadian clock. The goal of this project is to characterize this never described circadian process as well as the involved mechanisms.