An investigation into the involvement of angiopoietins in the development of colorectal cancer
1. Malignant Hyperthermia We continue to make progress with the identification and functional characterisation of further mutations in the RYR1 gene associated with malignant hyperthermia. These findings are being translated into patient benefit through introduction of further mutations into the diagnostic panel. This year we have conclusively demonstrated that a significant minority of UK MH cases are not associated with RYR1 mutations and other potential candidate genes are being studied.
Collaborators: Drs Shaw, Iles and Steele in Faculty of Biological Sciences and Prof PD Allen, Harvard Medical School
Funding: Department of Health, Big Lottery Fund
2. Sepsis Following on from successful projects investigating molecular mechanisms of effects of anaesthetics on the heart, we have been investigating direct effects of inflammatory mediators on the heart. A clinical project to identify genetic determinants of susceptibility to severe inflammatory response to cardiopulmonary bypass is also in progress
Collaborators: Drs Harrison and Steele in Faculty of Biological Sciences. Prof CS Reilly, Drs Ross and Brookes, University of Sheffield
Funding: British Heart Foundation, British Journal of Anaesthesia/Royal College of Anaesthetists
Figure 1. Time sequence of caffeine-induced calcium release from the sarcoplasmic reticulum in transduced transgenic differentiated “dyspedic” myotubes carrying a mutation in RYR1. Imaging was carried out using a confocal fluorescence microscope.
Robinson RL, Carpenter D, Shaw M-A, Halsall PJ, Hopkins PM. Mutations in RYR1 in malignant hyperthermia and central core disease. Human Mutation 2006; 27: 977-989.
Graham MD, Hopkins PM, Harrison SM. Antagonistic actions of halothane and sevoflurane on spontaneous Ca2+ release in rat ventricular myocytes. Anesthesiology 2006; 105: 58-64
Duke AM, Hopkins PM, Halsall PJ, Steele DS. Mg2+-dependence of Ca2+ release from the sarcoplasmic reticulum induced by sevoflurane or halothane in skeletal muscle from humans susceptible to malignant hyperthermia. British Journal of Anaesthesia 2006 ; 97: 320