Manchester Centre in Biological Timing in Disease
It is well known that circadian clock dysfunction contributes to the incidence and severity of many diseases, including inflammation and metabolic syndrome.
We know that the circadian clock is an underlying cause of fluctuations in disease activity, driving cycles in local joint inflammation and cell infiltration. However, until now there are few translational research programmes out there that focus on clock biology.
The newly launched Manchester Centre in Biological Timing in Disease is focused around four research themes and is supported by £500,000 of funding from The University of Manchester, as well as individual research grants totally £24 million, from a range of funders including the Biotechnology and Biological Sciences Research Council, Medical Research Council and Arthritis Research UK.
Working in collaboration with the NIHR Manchester Musculoskeletal Biomedical Research Unit, the centre will deliver cutting edge translational research latest research in shedding light on the role it plays in diseases and general health. The focus of the collaboration with the BRU is Professor Ray’s study into understanding how biological clocks are affected by rheumatoid arthritis, and if this offers a way to improve treatment response, by altering the timing of treatment.
The centre sees the largest research grouping in biological timing in Europe. The University of Manchester researchers have expertise in ultradian rhythms, timing control systems in development, seasonal or infradian rhythms and circadian rhythms. The access to the latest e-health resources and patient base and the NIHR / Wellcome Trust Central Manchester Clinical Research Facility which is co-situated on the Central Manchester University Hospitals NHS Foundation Trust site, means the centre has the ability it delivery phase 1-3 clinical trials.
The centre will embed circadian logic into clinical trials, and clinical care delivery in inflammatory and cardiometabolic diseases through the four themes below.
As mentioned above, the BRU is funding initiative 4A within the centre, led by Professor Ray. The study explores chronotherapeutic targeting of p38 protein in rheumatoid arthritis. Through this research the team hopes to find the expression, basal activity, and response to stimulation of the MAP kinases, including p38, are under circadian control. This will affect the expression of chronic inflammatory diseases, and also the response to therapeutic intervention.
Theme 1: Discovery and Development – Chemical biology approaches to target circadian clock control of chronic inflammation.
Initiative 1A: Chemical biology approaches; target identification, validation, proof-of-principle studies, and drug development
Initiative 1B: Targeting reverb in lung inflammation
Initiative 1C: Targeting CRY in CIA model of RA
Theme 2: Clinical enabling studies – Building clinical research infrastructure to investigate circadian factors in human inflammatory and cardiometabolic diseases.
Initiative 2A: Accessing the UK Biobank
Initiative 2B: Nested Studies in Rheumatoid Arthritis
Initiative 2C: Nested Studies in Asthma
Initiative 2D: CMFT-funded observational study in T2DM
Theme 3. Revealing the clock as a key determinant of inflammation-related metabolic disturbance.
Initiative 3A. Defining the metabolic and circadian signature of inflamed versus safe fat. Determining how lipid storage reciprocally affects the adipose tissue clock, and macrophage function
Theme 4. Proving the principle – Circadian based intervention to improve inflammatory and metabolic disease.
Initiative 4A. Chronotherapeutic targeting of signalling kinases in RA (initial focus on p38 SAPK)
Initiative 4B. REstoring FavouRablE Sleep to HElp patients with Diabetes (REFRESHED)
Initiative 4C. Maximising circadian amplitude and stability to minimise metabolic disturbance in RA 5