… a new level of confidence in the quality of our cell models.“
Dr. Jussi-Pekka Tolonen is a Marie Skłodowska-Curie Fellow in Professor Esther Becker’s lab at the Nuffield Department of Clinical Neurosciences, University of Oxford. He works on new models of genetic childhood-onset brain diseases. Prior to coming to Oxford, he trained as a child neurology registrar in Finland, having carried out his PhD training during medical school. We had the great opportunity to talk to him about his research
What motivated you to become a scientist and what drives you today?
During medical school, I was always interested in translational research but it became really relevant in child neurology. Child neurology is a very dynamic and fast-paced field when it comes to new developments like treatments or novel disease entities, but there are still so many paediatric patient groups who have few targeted treatment options available to them, if any. I really want to understand disease mechanisms in genetic disorders and to identify new treatment targets, for example, for drug development.
What is your main research interest?
I work with stem cells and stem cell-based disease models which we call organoids. It’s a relatively recent field where induced pluripotent stem cells – or iPSCs in short – are used to make three-dimensional models of potentially any tissue in the human body. In our case, we make brain organoids, specifically cerebellar organoids, to study how neurons in the brain function differently in disease. The Becker lab has developed robust methods to make these cerebellar brain organoids for disease modelling.
How do you make use of iPSC technology in your work?
The human brain is inaccessible to us, so it has been very difficult to study brain disorders on a cellular level. Induced pluripotent stem cells have really given us a new way to model the developing brain and therefore to study genetic diseases that manifest very early on. We can compare organoids that have been generated from “normal” iPSCs and iPSCs that carry the disease-causing mutation, while keeping the genetic background constant, and this has so far been possible only using mice which are a very different organism.
What are some of the challenges you face working with iPSCs?
Despite the promise that iPSCs carry for brain diseases, there are obviously some obstacles that we need to overcome. For example, generating isogenic iPSC clones can be inefficient, especially if studying missense disease variants where only a single nucleotide has changed. Similarly, brain organoids are still more of a developmental model, so a lot of the proteins that are involved in adult-onset disorders may not be highly expressed yet. Therefore, we need to be able to generate more mature brain organoids and neurons.
How did you know learn about iotaSciences?
We heard about iotaSciences by word-of-mouth, and it was a very exciting opportunity to try and speed up the process of generating genome-edited iPSC clones. We have produced mutant iPSC lines with more traditional flow-sorting approaches, but this is very tedious, with often poor cloning efficiency and uncertain with regards to clonality. iotaSciences’ knowledge-driven approach and their streamlined workflow, has allowed us to quickly obtain desired clones and move our project forward. The additional assurance of monoclonality through visual confirmation and documentation gives us a new level of confidence in the quality of our cell models.
Thank you very much for your time!