Focus on research: Prof David Henshall, FutureNeuro
Prof David Henshall is centre director at FutureNeuro, the Research Ireland centre dedicated to diagnostics, therapeutics, and e-health for patients with neurological, psychiatric, and neurodevelopmental disorders. Here he discusses the plans for the centre after a successful six years and his new book Fine-Tuning Life.
FutureNeuro just passed a significant milestone. How has it scaled to far?
The centre began in 2017. We ran for six years and then we went through a competitive international peer review. To assess the quality of the science that we were doing and other aspects of what the centre works on and we passed with flying colours and Science Foundation, and SFI gave us then a further six years of funding to continue the research, and also to move in some new and exciting directions.
The centre started with a team 13 or 14 scientists and a small operations group of about three or four members that supported the centre. We now have 30 science teams and in terms of research projects, we’ve probably got 3x since we since we began. We’re in eight universities, and Institutes of Technology. So, it’s sort of a fully national research centre.
You’re reaching a lot of patients. Has that experience changed the way the centre operates?
How patients with complex brain diseases are managed has changed very dramatically and become more multi-disciplinary. The management of a patient with a complex brain disease might include genetic testing, genetic counselling, there may be brain imaging involved, brain recordings, psychology, psychiatry. It might lead through to neurosurgery and pathology. Tackling complex brain diseases is a big team sport.
In the ‘olden days’ you might have a team of neuroscientists working on a problem or you might have a team of geneticists. What we can do with FutureNeuro is bring together everyone we think is needed for a particular problem.
For example, if it’s something around diagnosis we can have genetics people, we can have neuroscientists and people who can study and understand electrical signals within the brain, all the way through to chemists and people that work with materials to develop test kits. You could never do that without a centralised mechanism where everyone concentrated on little jobs in their parts of the world.
The centre means that everyone can work together on difficult problems.
We’re all still learning how to talk to each other. We’ve got some people who are basically computer scientists and mathematicians who come from a very different school of communication than the biologists, then people who come from the social science and humanities area. Bringing them together is sometimes difficult. You have to appreciate each other’s style of working and understanding.
For example EEG (electroencephalogram) recordings are to some degree an engineering problem. It’s about electrical signals – converting them, studying them, understanding them – but the kind of the people that know how to understand electrical signals come from a different background and training to the people who want to apply that knowledge. A doctor might react: “Well, you’re telling me all of this signal stuff. What does that? How does that affect how I look after my patient?”
Another example would be a computer scientist who might come in and say, “well just give me all the data. Give me all the data and I’ll kind of crunch through. I’ll use my AI, my machine learning, and I’ll give you the answer.” A clinician might tell them they just can’t have that.
The stuff that works comes from a back and forth developed over time.
You’ve just had a book released, Fine-Tuning Life. Tell us a little about it.
I’ve always been interested in how we can cure epilepsy because the treatments that we have at the moment are not very effective. The approach my lab have taken for years has been to see what is different in the part of the brain that causes a seizure, and if we can understand that, we may learn what is causing epilepsy.
If we know what causes something, we have a chance to design a new type of drug.
What we learned early on was that the activity of many, many genes – hundreds in fact – in those brain regions that trigger seizures was altered. There was never going to be a sort of Magic Bullet that that could change that gene activity back to how it should be.
I started looking for new ideas for how to change the activity of many genes at once. And if you could kind of find a sort of ‘master controller’ or ‘master regulator’ of genes, then you had an opportunity to correct a lot of genes all at once.
I was on the lookout for that master controller. Around the time that that search process began this discovery came out that there was, in fact, a new type of gene in the human genome, which had previously been invisible. It had been largely ignored or at least wasn’t understood. And that gene was called a micro-RNA. As we learned more about this type of gene, it turned out these microRNAs are our master regulators. That led to the research that we’ve been doing ever since, which is to find out if we can we drug these new types of genes – either through gene therapy or some other approach – to target that type of gene and hopefully treat or cure epilepsy?
It’s kind of the end point of what the centre is interested.
Essentially. There are three parts of the research in the centre: diagnosis, therapeutics and e-health.
Therapeutics – drug discovery and drug development – is my passion. Our tagline is basically ‘to produce the next generation of disease-modifying therapies’.
What our research has been showing over the last few years is that targeting this type of gene is a way to achieve that that goal. And so, the book came from our research and then me kind of taking a bit of a step back and getting very excited about these genes.
So as I tried to learn more and more about it: How they were discovered? Why they evolved in the first place? Why do we have this sort of separate gene system in our genome? What do they do in the body as we develop? What do they do in the brain? In later parts of the book I look at how the science of this gene has led to applications as medicines and diagnostic tools.
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