First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Hannah Black and Rachel Livingstone are co-first authors on ‘ Knockout of syntaxin-4 in 3T3-L1 adipocytes reveals new insight into GLUT4 trafficking and adiponectin secretion’, published in JCS. Hannah conducted the research described in this article while a PhD student in Professor Nia Bryant and Professor Gwyn Gould's lab at the Henry Wellcome Laboratory for Cell Biology, University of Glasgow, UK. She is now a postdoc in the lab of Professor Nia Bryant at the Department of Biology, University of York, UK, investigating membrane trafficking of the glucose transporter protein GLUT4. Rachel is a PhD student in the lab of Professor Gwyn Gould at the Henry Wellcome Laboratory for Cell Biology, University of Glasgow, UK, where she is also investigating membrane trafficking of GLUT4.
How would you explain the main findings of your paper in lay terms?
H.B. and R.L.: Fat cells, known as adipocytes, play an important role in controlling blood glucose levels. When blood glucose levels are high, insulin is released from the pancreas, and as a result glucose is taken up by the adipocytes via a specialised protein called GLUT4 and, therefore, blood glucose levels fall back to normal. Dysregulation of blood glucose levels can lead to insulin resistance and type II diabetes. Syntaxin-4 is a protein that has been proposed to play a role in insulin-stimulated glucose uptake in adipocytes.
By generating cells lacking the syntaxin-4 protein, we were able to demonstrate that these cells had a 50% reduction in glucose uptake in response to insulin compared to that of cells containing syntaxin-4. In addition, adipocytes release small proteins called adipocytokines, which communicate between cells and are involved in metabolism. Cells lacking syntaxin-4 also showed a 50% reduction in release of the adipocytokine adiponectin, suggesting that syntaxin-4 has an important function in many aspects of adipocyte biology as well as glucose transport.
Were there any specific challenges associated with this project? If so, how did you overcome them?
H.B.: Working jointly on this project across two institutions, York and Glasgow, posed a logistical challenge at times. Even pre-pandemic we were used to setting up regular video meetings to make sure that we were all on the same page and the work could progress most efficiently.
R.L.: Coming from a clinical background meant that working in a laboratory was a new environment for me. Initially this felt very intimidating, but I was lucky to have an incredibly supportive lab group and supervisor who helped me every step of the way. I spent a lot of time practicing and trying to familiarise myself with the techniques, as well as understanding the underlying scientific basis. Once I started seeing results come together it was very satisfying, and this motivated me to continue.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
H.B.: This was my first time using the CRISPR-Cas9 method of gene editing. I was excited to gain some experience of this relatively new and versatile methodology and so, after some optimisation, the moment when I confirmed that I had made successful knockout cell lines was very rewarding. I have taken what I learned from this project and applied it when using CRISPR-Cas9 editing in subsequent work.
R.L.: The most exciting finding for me was the reduction in adiponectin secretion, as this was not necessarily something I was expecting to find. This, along with the corresponding increase in intracellular levels of adiponectin, suggests that syntaxin-4 plays a wider role in adipocyte biology. It was at this point that I finally believed in my abilities to plan and execute experiments in the lab, and this helped build a broader understanding of the role of syntaxin-4.
Why did you choose Journal of Cell Science for your paper?
H.B. and R.L.: Journal of Cell Science publishes high quality papers and is renowned in the field of cell biology. We felt that our paper would be a very good fit for the scope and readers of this journal, and we are delighted that it has been published.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
H.B.: I count many of the talented researchers that I've met over the years as mentors. The best inspiration often comes unexpectedly, and I've had countless influential conversations in hallways, in meetings and over coffee with many of my colleagues.
R.L.: I could not have asked for a more supportive supervisor than Professor Gould. He understood the challenges I faced throughout coming from a non-scientific background and was always there to encourage me, giving me the confidence to keep going when I encountered difficulties. He was understanding about the balance of continuing to work as a clinician on night shifts as well as running a clinical study, and he was always willing to feed my cells if needed! Finally, he shares my love of running and provided much needed motivation during periods of injury and marathon training!
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?
H.B.: At school, I found science interesting, challenging and constantly changing in a way that other subjects weren't. I've been lucky to work with some great supervisors in my career so far, which has meant I have always found it enjoyable and rewarding – even when experiments haven't been going so well!
R.L.: After starting my undergraduate degree in medicine, I completed an intercalated BSc degree in Pharmacology, where I undertook a lab-based project. This was my first taste of science, and I really enjoyed the satisfaction of performing experiments and seeing results come together. Once I started my specialist training in Diabetes and Endocrinology, I knew I wanted to pursue further research. This was the perfect opportunity for me and is one that I am extremely grateful to have had.
What's next for you?
H.B.: I'm currently enjoying some time with my 5-month-old daughter on maternity leave and I'll be looking for a new position in the new year. I'm excited to explore any interesting opportunities, either in research or outside of academia, where I can continue to use the analytical and problem-solving skills I've built over the years.
R.L.: Following my research post, I have returned to being a full-time clinician. I continue to have a specific interest in type II diabetes, including the underlying pathophysiology of glucose transport, and I look forward to seeing where this field takes us. Following my research, I have developed many transferrable skills that are helpful in my day-to-day clinical work. I am still interested in academia and may come back to it, but for now my focus is on completing my clinical training.
Tell us something interesting about yourself that wouldn't be on your CV
H.B.: I love to cook (and eat!). Since giving up meat a couple of years ago, my partner and I are constantly on the lookout for new and exciting recipes to try. Despite cutting out a food group, our diets are more interesting and varied than ever!
R.L.: Having grown up in the countryside, I love to be outdoors and find that the fresh air always helps to clear my mind. I am a keen runner and have run two marathons so far. The first was the Loch Ness marathon, and the second was the London marathon, which I ran while expecting twin boys. I am hoping to find time to get back to running longer distances soon, but for now running around after two toddlers is more than enough!
Hannah Black's contact details: Department of Biology, University of York, York YO10 5DD, UK.
Rachel Livingstone's contact details: Henry Wellcome Laboratory for Cell Biology, Institute for Molecular, Cellular and Systems Biology, College of Medical Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.