Junior Research Fellow Reports on Recent Research

Dr Rebecca Anne Capel is a Campion Hall Junior Research Fellow in the Universitys Department of Pharmacology, where she is engaged in a joint research project funded by the Wellcome Trust and the Royal Society. She writes of her recent research and conference activities:

 

Earlier this year it was my great pleasure to give one of Campion Hall’s Work in Progress presenta- tions, in which I presented our idea that lysosomes, a structure within cells that has traditionally been considered as a waste processing unit, actually take part in acute signalling within the heart.

Every time a heart cell beats, electrical activation of the cell (which is generated spontaneously by a specialised area of the heart) causes a big increase in the amount of calcium within the cell. This calcium, far from being the natural component of bones and teeth, is dissolved in the fluid around and within cells and is essential for both causing contraction and controlling many processes happening within the cell.

Calcium hard at work

We now know that cells are capable of storing large concentrations of calcium within lysosomes. Work during my DPhil studies confirmed that this calcium can be released in response to specific sig- nals, particularly related to stressful situations, and help to increase the strength of the heart’s contraction. The latest developments in our research, which I presented at my Work in Progress, were recently published in Scientific Reports titled “High resolution structural evidence suggests that Sarcoplasmic Reticulum forms microdomains with Acidic Stores (lysosomes) in the heart”. This publication, using a range of microscopy techniques, shows that lysosomes, and therefore the sites from which calcium can be released, are not randomly positioned within heart cells but are placed just 3.3 nano-metres (a human hair is around 75,000 nanometres thick) from the most important known contributor to cellular calcium signalling.

We also found that lysosomes are just 6.2 nm from mitochondria, where cells make most of their ener- gy in the form of ATP. This means calcium com- ing out of the lysosome is immediately positioned to affect essential ‘traditional’ signalling areas. In the future it will be vital to see if these spatial rela- tionships are changed in diseases like atrial fibrilla- tion, as this may help us to understand the reasons why calcium signals are perturbed in these patients and provide a potential therapeutic target.

Controversial but exciting

In February I took our work, together with some data showing the functional effects of abolishing lysosomal calcium signalling within heart tissue, to the Gordon Research Conference on Cardiac Arrhythmia Mechanisms, held in Ventura, California.

Gordon conferences are specialised conferences to which you must make application and be selected in order to attend, and this was therefore a fantastic opportunity for me to show our work to the top scientists in the arrhythmia field. I was able to speak to some of my personal heroes, and I was given advice on experiments I might like to perform in the future. For me the highlight of the Conference was having our work labelled “controversial but exciting”, and my being awarded, to my delight, the prize for the best post-doctoral poster presentation.

Having a heart

Members and friends of Campion Hall who would like to find out more about our work were invited last month to visit the exhibition “Science Museum Lates” in the South Kensington Science Museum in London , in which the Burton Group, for which I work, was taking part. During the event the Science Museum was open after hours for adults only, and a number of talks and exhibits were on offer, together with a bar and silent disco.

We also took a machine to show people the electrical activity in their own hearts and link this to the work we do recording electrical events in cells and tissue. We also took different models of hearts and some fixed tissue from the butchers, so that inter- ested punters could literally poke around and get to know this awesome organ. We hoped in this way to give people an idea of how electricity drives their heart and how researchers can use these events to study disease.

 

--Text courtesy the Editor, Campion News. Find a link to our current issue on the top of the News page