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. Anna Gavrilova is first author on ‘ The role of kinesin-1 in neuronal dense core vesicle transport, locomotion and lifespan regulation in C. elegans’, published in JCS. Anna is a PhD student in the lab of Viki Allan at the University of Manchester, UK, investigating experimental studies, data analysis and mathematical modelling of intracellular transport.
Anna Gavrilova
How would you explain the main findings of your paper in lay terms?
Cells have a transport system that's crucial for their health, similar to how a city's transport network is essential for moving people and goods around efficiently. Inside cells, microtubules and actin filaments act like roadways, guiding motor proteins that transport important molecules and organelles to their destinations. Just like a city's transport network must adjust to changes and obstacles, the cellular transport system also adapts to the cell's needs and environment. Disruptions in this transport system can lead to problems, much like traffic jams can affect a city's function. Our research focused on understanding this transport process in neurons, one of the longest and most complex cell type. Using the nematode worm Caenorhabditis elegans, we used advanced imaging to watch tiny cell structures move in real time, which helped us see how different parts of the transport system work in neurons. We experimented with modified versions of the motor protein kinesin-1 to see how these changes affected the movement of organelles. Our study revealed that kinesin-1 is crucial for directing and regulating the speed of vesicle transport. We also discovered that different mutations in the kinesin-1 system affect not just transport but also the worm's longevity and ability to move. These findings could help us understand and potentially treat diseases in which cellular transport goes wrong.
Were there any specific challenges associated with this project? If so, how did you overcome them?
My main challenge with this project was transitioning from a theoretical and applied mathematics background to working in a lab setting. Initially, everything in the lab was new and unfamiliar to me given that I had no prior experience in experimental work before starting my PhD. This challenge was actually exciting because it pushed me to learn and adapt quickly. I had to get up to speed with various techniques, such as working with worms, crossing them, doing PCR, imaging and especially microinjection. Another significant challenge was integrating my mathematical skills with biological research. To address this, I carefully planned each experiment, including how to analyse and model the data. The support of my two advisors, Viki Allan in biology and Sergei Fedotov in mathematics, was invaluable in overcoming these challenges. Their guidance helped me adapt and effectively combine my mathematical expertise with the practical aspects of biological research.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
The most exciting moment in my research came when I reviewed the lifespan data and realized we had accidentally significantly extended the lifespan of some strains of mutant worms. This was an unexpected outcome, as our initial focus was solely on studying intracellular transport within neurons. Discovering that mutations in motor proteins could affect not only the transport of tiny organelles but also the overall lifespan and behavior of the entire animal was a revelation for me. It was thrilling to see how interconnected these biological processes are and how a single factor can influence multiple aspects of an organism's life.
ALA neuron structure and dense core vesicle distribution. (A) Spinning disk fluorescence images of an ida-1::gfp worm showing the dense core vesicles (DCVs) (inverted LUT). Scale bar: 100 μm. An enlarged section of the ALA neuron, a mechanosensory interneuron, is shown in the red box. (B,C) Spinning disk fluorescence images of an unc-116(rf);ida-1::gfp;ebp-2 worm showing (B) EBP-2::mScarlet, which labels microtubules, and (C) IDA-1::GFP, which labels DCVs (inverted LUT). In contrast to a straight morphology seen in the ALA neuron in non-mutant worms, the ALA neuron is branched in a 10-day unc-116(rf);ida-1::gfp;ebp-2 worm with a kinesin heavy chain (KHC) mutation. The neuronal morphology of a worm older than 10 days is significantly altered compared to small branches seen in day-1 adult worms. Scale bars: 10 μm.
ALA neuron structure and dense core vesicle distribution. (A) Spinning disk fluorescence images of an ida-1::gfp worm showing the dense core vesicles (DCVs) (inverted LUT). Scale bar: 100 μm. An enlarged section of the ALA neuron, a mechanosensory interneuron, is shown in the red box. (B,C) Spinning disk fluorescence images of an unc-116(rf);ida-1::gfp;ebp-2 worm showing (B) EBP-2::mScarlet, which labels microtubules, and (C) IDA-1::GFP, which labels DCVs (inverted LUT). In contrast to a straight morphology seen in the ALA neuron in non-mutant worms, the ALA neuron is branched in a 10-day unc-116(rf);ida-1::gfp;ebp-2 worm with a kinesin heavy chain (KHC) mutation. The neuronal morphology of a worm older than 10 days is significantly altered compared to small branches seen in day-1 adult worms. Scale bars: 10 μm.
Why did you choose Journal of Cell Science for your paper?
I chose to submit my paper to Journal of Cell Science because of a memorable experience at the JCS Journal Meeting on Imaging Cell Dynamics held in Lisbon in May 2023. During the conference, I had the opportunity to meet the journal Editors and was impressed by their enthusiasm and commitment to advancing the field. Their passion for the journal and its role in the scientific community convinced me it would be the perfect venue for my 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?
My motivation to pursue a career in science comes from growing up in a family with diverse interests: half are in medicine and biology and the other half are in mathematics and economics. From a young age, I was torn between my love for both biology and mathematics. I initially chose to focus on mathematics, but with support from the Wellcome Trust, I am currently pursuing a PhD in biology, where I can apply my strengths in combining mathematics, data science and biology. One of the most exciting moments in my journey has been seeing how this multidisciplinary approach can enhance research and uncover new insights. I genuinely believe that blending these fields will become increasingly valuable in the future, and it's exciting to be at the forefront of this integration.
What's next for you?
I'm focused on completing my PhD, and I'm currently in the process of looking for a postdoctoral position. So wish me luck as I embark on this next chapter of my scientific career!
Tell us something interesting about yourself that wouldn't be on your CV
I'm a big anime fan! During the stressful periods of writing my PhD thesis, watching anime episodes became my main form of relaxation. I'd often unwind by watching one episode during breaks and a few more before bed. Comedy and romantic animes in particular provided a great distraction and helped me de-stress. It's amazing how something as simple as a good anime can effectively balance the demands of intense academic work with a bit of fun and relaxation!
Anna Gavrilova’s contact details: School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, The Michael Smith Building, Rumford St, Manchester M13 9PT, UK.
E-mail: [email protected]
