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. Tina Angelika Schrader and Ruth Carmichael are co-first authors on ‘ PEX11β and FIS1 cooperate in peroxisome division independently of mitochondrial fission factor’, published in JCS. Tina Angelika is a senior research technician in the lab of Prof. Michael Schrader at the College of Life and Environmental Sciences, Biosciences, University of Exeter, UK, where her area of expertise is culturing and manipulating mammalian cells, as well as implementing new scientific ideas and directions. Ruth is a Postdoctoral Research Fellow in the same lab, who is interested in the fundamental physiological mechanisms and regulation of organelle dynamics (e.g. their shape/morphology, number and interorganelle interactions) in mammalian cells, and the impact of this on health and disease.

Tina Angelika Schrader (left) and Ruth Carmichael (right)

How would you explain the main findings of your paper in lay terms?

T.A.S. and R.C.: Peroxisomes are small, usually spherical compartments within our cells that are essential for human health, playing important roles, including making and breaking down specific fat molecules. When the cell needs to make more peroxisomes, it typically does this by stretching out the existing peroxisomes, then ‘pinching off’ new spherical peroxisomes from this elongated structure, like making sausages. It was previously thought that a protein called MFF was essential for this ‘pinching off’ – indeed, patients that do not have the MFF protein have very long, spaghetti-like peroxisomes, as their peroxisomes can still elongate but can't be divided. However, using cells from these MFF-deficient patients, we discovered that we could get these very long peroxisomes to divide, in the absence of MFF, by increasing the amount of another protein called PEX11β. This suggests that there is a second, novel route for dividing peroxisomes that doesn't use MFF but instead needs PEX11β (and, we found, another protein called FIS1). This discovery could be therapeutically beneficial, allowing us to bypass a compromised pathway in certain patients to restore healthy peroxisome division.

Were there any specific challenges associated with this project? If so, how did you overcome them?

R.C.: Much of the work in this project was performed in primary patient fibroblasts, which we used as models for loss-of-function of our proteins of interest; however, they can be tricky to culture and especially to transfect. Luckily, Tina is an expert in mammalian cell culture and microporation, so by joining forces we managed to make it work!

T.A.S.: I agree that establishing the techniques to investigate the two different division pathways was the biggest challenge. On a personal level, I had to face the uncertainty of still being employed to drive and complete the work I started. Fortunately, by achieving grant funding to bring Ruth onto the team, we were able to shape and push this project forward.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

T.A.S.: I still remember the first peroxisomal staining I performed in the MFF-deficient patient fibroblasts 7 years ago. Our PI and I were sitting at the fluorescence microscope looking at the longest peroxisomes we have seen so far. This was the moment we realized that this is the perfect cell model to study the division process of peroxisomes.

R.C.: For me, having joined the lab once Tina had already generated this interesting and promising preliminary data, it was more a series of small ‘eurekas’ as we set out to characterize what regions of PEX11β were important for this MFF-independent peroxisome division. For each PEX11β mutant we expressed, it was exciting to find out (either way!) if we had disrupted peroxisome division, to gradually piece together a mechanistic picture of this process. It definitely threw up some unexpected surprises as well, for example finding out the N-terminus of PEX11β (thought to promote elongation and enhance DRP1's GTPase activity) was dispensable for this form of peroxisome fission.

Why did you choose Journal of Cell Science for your paper?

T.A.S. and R.C.: As a project investigating fundamental cell biological processes and mechanisms, we felt like this paper fitted in very well with the scope of Journal of Cell Science. JCS has an excellent reputation for publishing exciting, cutting-edge and robust cell biology. You always expect, when reading a JCS paper, that it will be high-quality and interesting science that has been peer-reviewed by world-leading experts. Many influential and paradigm-shifting papers in the peroxisome field have been published in JCS, so it is encouraging to sit alongside them!

Immunofluorescence of a peroxisomal marker protein showing the highly elongated, spaghetti-like peroxisomes in MFF-deficient patient fibroblasts (left) that can divide into numerous spherical peroxisomes upon overexpression of PEX11β (right).

Immunofluorescence of a peroxisomal marker protein showing the highly elongated, spaghetti-like peroxisomes in MFF-deficient patient fibroblasts (left) that can divide into numerous spherical peroxisomes upon overexpression of PEX11β (right).

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

T.A.S.: I am very grateful that Prof. Michael Schrader has invested so much time to guide me not just technically but also on a personal level. By challenging me in various aspects of being a research technician, he gives me a boost of confidence and belief in myself every single day.

R.C.: I definitely agree – Prof. Michael Schrader has been, and continues to be, an excellent mentor. Not only is his passion for peroxisomes infectious, but he is incredibly supportive and nurturing to all of his team, and has given me many opportunities to develop myself and take on responsibility that I would not get elsewhere. Additionally, my PhD supervisor Prof. Jeremy Henley (University of Bristol), really helped build my confidence when I was starting out, as did my mentor for my first post-doc position, Dr Tim Craig (University of the West of England), by trusting me and encouraging my independence.

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?

R.C.: I was always curious about how the world worked as a child, and I remember being fascinated by the Royal Institution Christmas Lectures that are shown on TV in the UK every year. Aged 16, I was lucky enough to spend a few days in a molecular biology lab as work experience, and I was hooked! I went on to do a biochemistry degree, during which I did short research projects on yeast and plants, but it was my final undergraduate project that really inspired my passion for mammalian cell biology, with its direct applications to human health and disease.

T.A.S.: I was always very interested in biology and chemistry in high school. Even though I never saw myself as an academic, I was always keen to learn more about the practical side of science. Thus, I started vocational training as research technician at the University of Heidelberg and have worked in higher education ever since.

“All these women have proved to me that anything is possible with enough commitment and determination, and that you can have a successful career without sacrificing a healthy work–life balance.”

Who are your role models in science? Why?

R.C.: I was fortunate to have plenty of inspirational female role models during my undergraduate degree, from Directors of Studies running world-leading research labs, to kind and friendly post-docs supervising my project work. As a post-doc myself at the University of the West of England, I particularly admired Prof. Myra Conway, who juggled running a successful research lab, managing a large team, delivering excellent teaching and raising a family whilst still being down to earth. All these women have proved to me that anything is possible with enough commitment and determination, and that you can have a successful career without sacrificing a healthy work–life balance.

T.A.S.: My role models in science are all the amazing technicians, post-docs and PIs I met in my career of 25 years so far. Their enthusiasm, curiosity, kindness and the ability to take time out of their busy and demanding schedule to mentor, to teach, to do the research they are so passionate about really inspired me. They all have one particular feature in common – they all managed being successful but stay grounded at the same time and having a fulfilled life outside the laboratory.

What's next for you?

T.A.S. and R.C.: In the short term, we were successful in securing a grant to support us both to continue fundamental research in the Schrader lab, investigating the communication between peroxisomes and other organelles, which is very exciting. We are looking forward to continuing our successful research partnership together.

R.C.: Ultimately, I would like to have my own research group, combining my current interests with my previous experience from my PhD in molecular neuroscience, to investigate how organelle dynamics are important to maintain cell health in the brain.

T.A.S.: I would like to stay in academia because I love being a research technician. One of the best things working in academia is meeting so many amazing people and having a huge diversity of techniques and responsibilities.

Who knows, maybe I will work as a research technician in Ruth's own research group one day?

Tell us something interesting about yourself that wouldn't be on your CV

R.C.: I have been dancing since I was 4 years old, and still take classes in commercial/street dance. It makes a refreshing break from science!

T.A.S.: I love spending time with my two daughters (19 and 16 years) because they teach me to see the world through their eyes. My oldest daughter recently sparked my interest in star signs, horoscopes and tarot card reading.

Tina Angelika Schrader's and Ruth Carmichael's contact details: College of Life and Environmental Sciences, Biosciences, University of Exeter, EX4 4QD, Exeter, UK

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