| cardiovascular research |
By Dr Leanne Grech
Research Engagement Officer at the British Heart Foundation
A CUT ABOVE THE REST There is enormous power in being able to cut out, replace or turn off bad genes whenever we want – especially if that power is used to heal. Take BHF-funded researcher Dr Emily Noël for example. She’s using the genetic scissors to find out why mutations (or faults) in genes can cause babies to be born with heart defects. At the University of Sheffield, Dr Noël and her team are looking at how congenital heart disease develops, in particular studying the role of the cytoskeleton. Like the bricks and walls of a building, the cytoskeleton is the ‘frame’ of the cell, providing support, keeping structures in place, and giving the cell a definite shape. If the cytoskeleton is not organised properly, for example from a faulty gene, heart cells and the heart itself will not form normally, leading to babies born with heart problems. Dr Noël and her team will use CRISPR to change or remove cytoskeleton genes in zebrafish – whose heart develops in a similar way to humans. In doing so, they will work out which heart cells require these genes, what they do in the cells, and what happens when the genes do not work normally – which will ultimately help us to understand more about why people with faults in their cytoskeleton genes can develop heart defects. A PhD student working with Dr Noël will also use CRISPR in zebrafish to study why faults in molecules called Dock6 and Eogt can cause heart problems in people with AdamsOliver syndrome (AOS). AOS is a rare inherited disorder characterised by defects of the scalp and abnormalities of the arms, fingers, legs or toes – with approximately 20% of babies born with the condition also having a heart defect.
| BIOSCIENCE TODAY |
IT’S CUTTING-EDGE TECHNOLOGY A bit further south, at the University of Keele, we have awarded funding to Dr Vinoj George who will use the power of CRISPR to study an inherited disease of the heart muscle called arrhythmogenic right ventricular cardiomyopathy (ARVC). In ARVC, faulty genes stop heart muscle cells (or cardiomyocytes) from sticking together correctly. As a result, the cells die and are replaced with fatty scar tissue, preventing the heart from pumping blood properly and causing abnormal heart rhythms. Combining CRISPR with a technology called optogenetics (which uses light to control cell behaviour), a PhD student working with Dr George will create 3D models of ARVC. First, they will introduce a mutation associated with severe ARVC into human stem cells, which have the potential to develop into any type of cell in the body. They will then allow the stem cells to grow into mature heart muscle cells on a 3D frame or scaffold. It might sound like science fiction, but new knowledge obtained from these models could help us to identify genetic differences linked to more severe forms of ARVC and reveal new ways to combat this disease.
A PAIR OF GENES Even further south, at the University of Birmingham, a PhD student working with Dr Neil Morgan is using CRISPR to study thrombocytopenia – a condition where someone has low levels of platelets in their blood. Platelets are cell fragments which can clump together to form a blood clot after an injury and so prevent excessive bleeding. People with thrombocytopenia can be prone to bruising, bleeding gums and nosebleeds as their blood is less able to clot. Dr Morgan and his team discovered that some people with this condition have faults in a gene called SLFN14. Using
It might sound like science fiction, but new knowledge obtained from these models could help us to identify genetic differences linked to more severe forms of ARVC and reveal new ways to combat this disease. 22