Calcium-permeable channels and their associated mechanisms and therapeutic potential

The work aims to understand the roles and therapeutic potential of a family of signalling proteins in cardiovascular physiology, cardiovascular disease and cancer.

It involves both novel research and translational research – research which seeks to progress novel understanding towards new or improved therapies. The signalling proteins enable detection of physiological and adverse stimuli and transduce these stimuli into permeation of calcium ions and other ions across cell membranes. The permeation signals to cells to change, for example to enable restructuring of a blood vessel as an adaptive process with beneficial or adverse implications (physiology or disease); adverse restructuring underlies aneurysms, for example, for which there is no current medical treatment.

In the research these restructuring processes are studied in mice as a model of humans and their disease. The roles of proteins are determined using genetic modifications and chemicals designed, usually by us, to specifically modulate the proteins. The research uses carefully designed experimental protocols with professional statistical planning and analysis to maximise the benefit from the experiments and minimise the numbers of animals required. It uses new preclinical imaging methodologies to enable non-invasive analysis, akin to how imaging methods are used in hospitals to detect and quantify disease progression.

Extensive in vitro cell-based experiments are performed in advance to inform decision-making about which research should progress to animal studies. The in vitro studies include studies of cells and tissues from patients so that we can know if findings are likely to be relevant to patients in the long-term, before any animal studies are performed. Our track-record shows that we can use such approaches very effectively to reveal important new understanding and use it to establish new drug discovery projects.

We are now taking the next important steps, with increased emphasis on translation. Our research direction has been approved by anonymous independent international peer-review and the world’s best research funding agencies. It is of the utmost priority to us that the very best possible animal care and welfare is achieved at all times.

Non-technical summary 

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