Wolfson Institute for Biomedical Research


Scanning electron micrograph of the dendrites of a cerebellar Purkinje cell - Hausser Lab


Matthew Swire

Project info:

In the vertebrate brain and spinal cord, oligodendrocytes construct a fatty insulating layer around axons. This insulation, called myelin, greatly speeds up the electrical signals sent by neurons as well as providing energetic support to neurons and their axons. Recently it has been demonstrated that oligodendrocytes and the myelin that they make also help the brain to adapt to new experiences, contributing to learning and memory formation. How exactly myelin influences learning is still not well understood.

Our hypothesis is that oligodendrocytes can sense the neurons that are activated by specific behaviours, resulting in the formation or remodelling of myelin on those active neurons. We predict that this process will fine-tune electrical signals and alter the connectivity of the active neurons leading to the development of new neuronal circuits responsible for new behaviours.

In this project we will train mice to learn a new motor skill and observe how the myelin on activated neurons changes with learning. We will then use genetic manipulations to disrupt pathways that may enable oligodendrocytes to sense neuronal activity and determine if these mice maintain the ability to learn motor skills. We will also disrupt the formation and maintenance of new myelin that is formed during skill learning to ask how this process changes neuronal connectivity.

Our experiments will help illuminate the general mechanisms underpinning one of the fundamental functions of the brain - the ability to adapt - and may provide insights into how better to maintain cognitive ability during healthy aging, or to aid recovery of brain function following disease or injury.

Fellowship Experience

I was awarded an MRC Career Development Award to support the investigation of how oligodendrocytes alter neural circuits during learning. This is a personal fellowship award that supports postdocs seeking to transition to independence by providing research staff costs and expenses for up to 5 years.

My application took 6 months in total, starting with writing a research proposal that address a question within the MRC’s remit of preventing illness, developing therapies and improving human health. This 6 page document needed to include details of the importance of the research, experimental approaches and the research environment. It must be your own ideas and not significantly overlap with those of your current supervisor.

After submission, the MRC send my proposal to 5 expert reviewers who provided an assessment of myself as an applicant, the proposed research and the host institute environment. Based on the scores from these reviews I was invited to an interview. The interview consisted of a 5 minute presentation of my proposal followed by a 25 minute interview by the MRC Non-Clinical Training and Career Development Panel. The questions during the interview focused on the concerns raised by the reviewers, how I plan to establish myself as an independent researcher and the implications of the findings. The panel then scored the proposals and funding was awarded to a number of the highest scoring applicants.

Throughout the application process I was incredibly fortunate to receive advice and support from colleagues both within UCL and further afield including feedback on the research proposal itself and 4 mock interviews. I am incredibly grateful for the time and input I received which was absolutely integral to the success of the application.

I would highly recommend postdocs who wish to set up their own lab at UCL to apply for this scheme and am very happy to discuss my experience in more detail.