"CLOCK-off Time" for inflammation and remodelling in chronic inflammatory diseases: Casein Kinase 1 delta inhibitor

Summary The group is investigating inflammation and fibrosis mechanisms using novel bioassays for target identification and drug discovery and characterisation. A range of system pharmacology-based analytical approaches are applied using transcriptomic and proteomic data from well-qualified clinical and experimental specimens. The lab has extensive links to Biomedical Engineering, Chemistry, Physics and several clinical centres and is the headquarters of the ARC-industry Transformation Training Centre in Personalised Therapeutic Technologies.

Project Details

The group is investigating inflammation and fibrosis mechanisms using novel bioassays for target identification and drug discovery and characterisation.  A range of system pharmacology-based analytical approaches are applied using transcriptomic and proteomic data from well-qualified clinical and experimental specimens.  The lab has extensive links to Biomedical Engineering, Chemistry, Physics and several clinical centres and is the headquarters of the ARC-industry Transformation Training Centre in Personalised Therapeutic Technologies.  

Chronic inflammatory diseases (including asthma and chronic obstructive pulmonary disease) exhibit a marked time of day variation in symptoms, airway inflammation and airway physiology. There is growing evidence supporting that the molecular clock is important in the pathogenesis of chronic inflammatory diseases. If time of day is important, then it follows that treatment of chronic inflammatory diseases should also be tailored to the most efficacious time of the day, known as "chronotherapy". Casein kinase 1 δ (CK1δ) has been implicated as a major regulator of the biochemical oscillator that determines circadian rhythm. Our laboratory has implicated CK1δ in signalling some of the fibrogenic and inflammatory actions of TGF-β, including the ability to switch off the anti-inflammatory effects of glucocorticoids. We hypothesize that CK1δ inhibitors reset the CLOCK to suppress inflammation. In this project, you will characterise the anti-inflammatory potential of CK1δ inhibitor class using primary human cells obtained from peripheral blood and/or from the airways. Methods to be used will include immunoassay, real-time quantitative PCR, cell culture and high content screening using plate-based confocal microscopy.