Professor Benjamin Blencowe is a new Professor at the Centre for Developmental Neurobiology at the IoPPN. He is also a Professor and Banbury Chair in Medical Research at the University of Toronto, and the Director of the University of Toronto’s Donnelly Sequencing Centre.
Please tell us about your new role in King’s
It started with a discussion with Professor Jernej Ule, a close colleague and collaborator of many years, about a project which involves the discovery and applications of what we refer to as RNA sensor-gating systems. We wanted to explore the application of RNA sensors to drive the expression of transgenes in a very context-specific manner to address the challenges of treating brain disorders.
We discussed the idea of working together at King’s, where I was already aware of a group of talented researchers in the broader neuroscience sphere, and it seemed like a wonderful potential opportunity. I approached Professor Oscar Marin here at the CDN and discussed the possibility of a part-time position. After visiting the CDN to learn more their work and meeting with the other group leaders, Oscar very generously offered me a position.
Together with Professor Jernej Ule and Dr Laura Andreae as co-principal investigators, we successfully obtained the Wellcome Discovery Award to advance this project to explore potential gene therapies for autism spectrum disorder and Alzheimer’s disease.
What do you think will be the biggest challenge to this project?
In terms of the science, it is ambitious. The major problem in treating brain disorders is you have subsets of neurons that are affected in individuals, and often these changes can happen before symptoms arise. The goal is to have a system where you can switch on a transgene that rescues the loss of function in only the affected neurons. So, it’s really a common problem despite the fact that disorders can be very different in their presentations.
There’s a lot we don’t understand in terms of how processes involving RNA biology are dysregulated in these disorders. To design sensor-gating systems, we need to identify the strongest and most robust RNA signatures that we can harness. Discovery is therefore a major part of the initial stages of this project. We need to find the best and most efficacious RNA signatures by comparing data from the human brain and disease models where genes known to be deficient in the brain disorder have been perturbed.
Previously in my Toronto group, we discovered an RNA signature that is commonly dysregulated in autism and this involves very short coding segments, called microexons, that look to be a promising signature that we can harness.
The technologies we will be developing with Professor Jernej Ule and our collaborator Professor Pietro Fratta (UCL) have been applied to Amyotrophic Lateral Sclerosis in their recent pioneering work, and can be extended to a range of brain disorders. This approach has tremendous promise to advance the discovery of new systems of rescue in the contexts of autism and Alzheimer’s.
This project is complex, so we will be drawing on expertise within and beyond King’s as well as using some findings from my Toronto group. I believe we have the right expertise to drive this project, especially with the amazing talent pool in London itself. It will be a valuable training opportunity for new lab recruits and I hope to arrange some exchanges for our researchers.
What are you most looking forward to?
I’m looking forward to establishing a thriving collaborative group in London where we’re contributing important research towards the goals of our Wellcome Trust grant. It is a truly exciting time in this field in terms of progress and we believe our project has tremendous potential.
I am also looking forward to the lively cultural scene in London, not to mention the weather. It is often too cold or too hot in Toronto, whereas here it’s somewhere in the middle, which I actually prefer!
How do you plan to divide your time between the UK and Canada?
I will still hold my position at the University of Toronto and will make multiple visits during the year to the UK to ensure I have a physical presence and to help facilitate a unified effort on our Wellcome Trust project.
I have wanted to return to the UK as I was born here and have spent many years, on and off, in this country. It is exciting being here at King’s with its vibrant campuses and activities.