First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Harry Scott is first author on ‘ The human discs large protein 1 interacts with and maintains connexin 43 at the plasma membrane in keratinocytes’, published in JCS. Harry is a PhD student in the labs of Professor Sheila Graham and Patricia Martin at University of Glasgow and Glasgow Caledonian University, UK, where he studies the role of Cx43 and Dlg1 in human papillomavirus-associated cancer and wound healing.
How would you explain the main findings of your paper in lay terms?
Communication between cells is vital for the survival of any organism. We investigated a protein called connexin 43 (Cx43), which is crucial for communication between neighbouring cells because it allows the sharing of chemical messengers. The amount of Cx43 on the cell surface has been previously shown to be altered in chronic wounds (wounds which do not heal over a period of 30 days). In this study, we showed that a scaffolding protein, discs large homologue 1 (Dlg1), interacts with and maintains Cx43 on the surface of human skin cells. Depleting Dlg1 resulted in Cx43 being trapped within the cell, which impaired cell–cell communication. As Cx43 has previously been shown to play a major role in wound healing, further research in this area could lead to the development of new therapies to help treat chronic wounds by altering the interaction between Cx43 and Dlg1.
Were there any specific challenges associated with this project? If so, how did you overcome them?
An important aspect of our research was to perform immunofluorescence staining of Cx43 and Dlg1 in human skin tissue. Our previously established system for collection of tissue was heavily disrupted by COVID-19, meaning there were large delays in tissue samples being taken and delivered to us. Through communication with the biorepository team at the hospital and Glasgow Caledonian University (GCU), I arranged to pick up the samples personally and helped reestablish the previous partnership, which should now mean other researchers will have easier access to samples from the GCU skin research tissue bank going forward.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
Cx43 is normally expressed on the plasma membrane, but this is reduced in cells with Dlg1 knockdown. It was important to figure out exactly where the remainder of the Cx43 was located in this scenario. After discussion, we decided to look at both the Golgi and the lysosomes by immunofluorescence and found an increased proportion of Cx43 in both of these organelles when Dlg1 was knocked down. Visually seeing the increase in colocalisation between Cx43 and the Golgi in this experiment was a really nice moment that confirmed we had the right idea.
Why did you choose Journal of Cell Science for your paper?
Journal of Cell Science is known for publishing cutting-edge research (including in the connexin field), so it felt like the right fit for our study.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I have been very lucky during my PhD to be part of an incredible lab group, which has supported and encouraged me to produce the best quality research. This especially applies to my supervisor at the Centre for Virus Research, Sheila Graham, who has taught me an amazing amount over the course of my PhD. I am also thankful for my supervisor at Glasgow Caledonian University, Patricia Martin, who can always be relied on for helpful advice. Finally, I am grateful for the funding I have received from the British Skin Foundation, which has allowed me to carry out this research.
What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?
In high school biology, I remember being really interested in the debate of whether viruses could truly be considered alive. Their uniqueness was definitely a driving factor in me going on to study biology further.
What's next for you?
Writing my thesis!
Tell us something interesting about yourself that wouldn't be on your CV
I'm a massive fan of live music and currently have two festivals I plan to attend this summer, that I'm going to have to fit in around writing somehow!
Harry Scott’s contact details: MacRobert Building, 464 Bearsden Rd, Bearsden, Glasgow G61 1QH, UK.