In the third of our series, we explore a ‘day in the life’ of Professor Cathy Abbott, a geneticist and leading researcher in the pre-clinical research team at the Muir Maxwell Epilepsy Centre.
I am a genetics researcher by training and based at the Western General Hospital at the Institute of Genetics and Molecular Medicine. I have become very interested in epilepsy over recent years because the gene I have been working on for a very long time has been found to be one that can cause epilepsy. So I have become an active member of the pre-clinical research team of the centre ever since!
During term time at the University I spend a lot of my day working in my office and attending meetings! I am the Director of Postgraduate teaching in the School of Molecular Genetic and Population Health Sciences so have a lot happening around this role. I also spend a lot of time writing either for journal papers or grant proposals. At present I am heavily involved in writing a grant proposal for the Athena SWAN initiative which initially supported women in science, engineering and technology, mathematics and medicine in higher education and research but has now been expanded to other minorities in all subject areas.
Throughout my day I also regularly have my PhD students popping in to my office to discuss their results. This is definitely my favourite part of the day! Sadly I don’t have the time to do lab work much myself these days, so it is great to have the opportunity to sit and chat about some piece of raw data and think together about what it could mean.
I do look forward to the summer break when I can actually spend time thinking more about science, writing research papers, and applying for research grants!
The biggest contribution to the work of the centre is that the gene I have been working on, the eEF1A2 gene, has shown to be mutated (or changed) in children with previously unexplained epilepsy - this has only been found in the last three years! This connection has finally been found because the capability to sequence people’s genomes (or work out how their DNA is structured) has become much easier over recent years, meaning that more people have had their genome sequenced, allowing more people with this particular gene to be identified. So it is really satisfying to know how my research can go on to help understanding epilepsy.
Most cases where this gene is mutated have been found in children with severe and devastating epilepsy, but as the sequencing has gone on and more information has been gathered different types of epilepsy with differing severities have been found. This is really interesting as it means that this gene has the potential to tell us a lot about different subtypes of epilepsy.
One of the things I have found most satisfying with my research is that I set up a website about this research for the families who have children with this gene mutation. The website contains a host of information about the research we are doing and our progress, but it also, very importantly, it connects families with others in similar situations. The website also has a comment function so it allows anyone to ask me questions about genetics and the biology of what is happening, making it easier for them to understand.
It is also a really great resource for other scientists and clinicians to see what work we are doing here on the gene mutation. If you are interested in reading more, see here (https://eef1a2epilepsy.wordpress.com/).
I really appreciate being able to meet other colleagues from around the Centre and hear about the research they are doing regarding childhood epilepsy as it inspires me and gives me the opportunity to be part of something bigger.
Yes, we have been greatly helped by Mike Cousin in exploring cell work and we will be collaborating with Iris Oren. I also seek clinical guidance from Dr Richard Chin on the clinical genetics side of things which is really useful. He is helping me write up case studies about particular children affected with this gene mutation to improve awareness of the mutation.
The short term aim is to find an answer to the question: what is happening in each case, when a single amino acid has changed, and why do we see different severities depending on the amino acid that has changed? Amino acids are arranged together to form proteins. Proteins have a range of functions from tissue to ion-transport channels and beyond. So we need to know whether the gene mutation is making the protein in the cell do something toxic (or preventing other proteins from doing their jobs) or whether the change just stops the protein in the cell from working properly.
This is a really important question because it can help tell us what type of drug could work with this type of epilepsy. For example, we need to find out if we have to increase the protein because the mutation means not enough of the protein is being produced, or if we have to decrease the protein because the mutation is causing the protein to turn toxic. If we get it wrong we could end up making the situation much worse.
We have some preliminary results that suggest that this mutation could be causing the protein to be toxic, so we definitely don’t want to try and increase the protein level in the cell in this case! Instead we need to try and suppress it.
A long term aim is then to hopefully find a drug that would work in this situation. A step towards this is by doing genome engineering in cells and animals, which has been extremely powerful and could lead to us an answer. However altering the human genome is hugely controversial and is not on the cards for anything that affects the brain.
Well I’ve just found out from one of my students that they have been able to engineer this mutation in neural cells completely cleanly – it is basically having the cells exactly as they would appear in a child with the mutation but in a way that we can manipulate and change. It is not easy to do and it is fantastic that it has been achieved! So now we can look at what goes wrong in these cells and how it could be affecting other aspects of the cells (e.g. synapses, ion-channels). I am very much looking forward to seeing where this takes us!
Having some time off and spending it with my family!