ABSTRACT
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. Anthony Dornan is first author on ‘ Compromised junctional integrity phenocopies age-dependent renal dysfunction in Drosophila Snakeskin mutants’, published in JCS. Anthony conducted the research described in this article while at Prof. Julian Dow's lab at School of Molecular Biosciences, University of Glasgow, UK, where he currently works as a Lab Manager/Research Technician. Anthony's research focuses on applying molecular genetic techniques, predominantly using the model organism Drosophila and in particular the fly's Malpighian (renal) tubules, to address fundamental questions in the physiology of cell signalling, transport and stress responses.
Anthony Dornan
How would you explain the main findings of your paper in lay terms?
Our group studies the kidney of Drosophila melanogaster (the common fruit fly), which essentially performs the same function(s) as the human kidney. Because the fruit fly has been studied for over a 100 years, we have a vast range of powerful genetic tools we can employ in our investigations. In our studies we were able to show that, as the fly ages, there is a natural decrease in kidney function. Coincident with this we showed that the kidney's cell junctions, analogous to ‘tight’ cell junctions in mammals, which join cells together creating a responsive protective barrier, also start to fail. This failure in the cell barriers means the kidney can no longer work effectively, while also allowing the possibility of infection. We were able to replicate this failure of kidney function by impairing expression of a particular gene called Snakeskin, which is involved in cell junction formation in the kidney. We hope that these studies will provide insight into the processes that underly age-associated tissue degeneration, and how this might then contribute to overall health.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Our investigations employed an intersectional stratagem to restrict the knockdown of the smooth septate junctional component Snakeskin to sub-populations of cells in the Malpighian (renal) tubules in the adult fly. This exquisite temporal-spatial specificity was only possible due to the power of molecular genetics techniques and reagents available for the model organism Drosophila melanogaster, the not-so-humble fruit fly.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
I originally started these investigations following on from work applying fluorescently conjugated dextrans to map water flux to the stellate cells in Drosophila and other invertebrates. I then set out to try and make a ‘leaky’ kidney and was astounded by the catastrophic effects that occurred when I impaired septate junction formation in sub-populations of cells in the fly's renal tubules. These effects are not just cell specific but affect tissue and whole animal viability.
Why did you choose Journal of Cell Science for your paper?
JCS has a history of promoting high-quality Drosophila research to a wider audience of cell biologists; specifically it has published works on Drosophila septate junctional components from the Furuse lab and other groups that our investigations complement.
A fluorescence image of a fly's kidney. A confocal image of a renal (Malpighian) tubule with nuclei (DAPI, blue), principal cells (mGFP, green), stellate cells (anti-Chloride Channel-a, magenta) and septate junctions (anti-Discs large, grey).
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
During the summer break before my final year as a Molecular Biology graduate, I was lucky enough to get an internship in the Dept. of Genetics in the lab of Kim Kaiser and was literally bewitched by Drosophila and the power of the molecular genetic techniques available you could apply to these tiny insects. From this moment working with Drosophila, I have never looked back. During this time I was mentored by Steve Russell, who put up with me while he completed work for his PhD and has remained a friend who encouraged me throughout my subsequent career, and became fast friends with Stephen Goodwin, who would later hire me to become his research technician when he started his own group, and then go on to supervise my PhD work.
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?
I have been interested in the sciences since I was in school, particularly the molecular biosciences. The opportunity to understand the genetic underpinnings that direct life appeared to me to be the most astounding endeavour anyone could pursue. Again, I would say I am incredibly lucky to have been allowed throughout my career to focus on Drosophila as a model organism and to have been part of the constantly exciting research community that drives molecular genetic studies in the fly.
Who are your role models in science? Why?
I have been lucky to have been exposed to a myriad of scientists throughout my career, whose enthusiasm and scientific rigour has inspired me, and whose generosity with their time and intellect have served to provide me with a template for my own behaviour. One such is my current PI, Prof. Julian Dow, who was my under-graduate project supervisor and provided a lab and safe haven at the University of Glasgow when my previous lab moved to Oxford. But without a doubt the person I owe the most with respect to my scientific career, who has inspired, supported and driven me as a scientist while also remaining a true friend, is Stephen Goodwin.
What's next for you?
I'm currently dividing my time between a BBSRC-funded research project in the lab applying single-cell and -nuclei sequencing in invertebrate kidneys, and pursuing my interests in supporting bioimaging at the University of Glasgow.
Tell us something interesting about yourself that wouldn't be on your CV
Despite having been born in Scotland and living the majority of my adult life here, my formative years were spent growing up in Toronto, to the extent that when I start to talk my accent makes people ask ‘where are you from?’ and my inevitable reply is Canada.
Anthony Dornan's contact details: School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, UK.
E-mail: [email protected]
