The life of a zebrafish heart expert
Dr Jana Koth from the MRC Weatherall Institute at the University of Oxford, tells us about growing up in Berlin, falling in love with science, and how she joined the BHF’s fight to mend broken hearts.
Discovering science
I first studied physiology and biology in Berlin. I decided to study for a year in Vienna but returned to Berlin to finish my diploma, looking at the heartbeats of butterflies and other insects.
Alongside my studies, I worked as a Student Assistant to the Director of the Max Planck Institute for Infection Biology. I did that, working crazy hours, for four years.
But I didn’t care. I adored the science and had a thirst to learn more.
After my diploma, I decided I’d like to travel outside of Germany and direct my work towards muscle cells. I was offered a PhD in King’s College London, looking at the development and repair of skeletal muscle in zebrafish. That’s when zebrafish started to grab my attention.
During my PhD, the key question I was determined to answer was: from which population of cells in the embryo do muscle stem cells come from?
I always found skeletal muscle fascinating. It is a unique cell type, with a unique purpose, and it repairs incredibly well. It was known at the time that satellite cells can repair skeletal muscle after damage or training, but it wasn’t known where this population came from. I used time lapse imaging of zebrafish larvae, to watch the muscle cells migrate right through the tissue.
With fish, you can study the development of muscle without disturbing anything, as the embryo is transparent.
For me, working with fish is incredibly exciting. Fish are such a powerful model organism. One can ask all sorts of questions, and over long periods of time.
The move to Oxford
As my PhD was coming to an end, a lot of people in the States had also started working on zebrafish. I knew I was onto something. I wanted to continue working with fish, and that’s when I saw the post-doc opening at the University of Oxford.
The team in Oxford had seen my work, and wanted me to join them in their fight against heart disease. I couldn’t wait to get stuck in, especially as I had a personal link to heart disease…
When I was in my 20s, my best friend had a heart attack.
She had a heart attack aged just 28. When something that significant happens to your best friend, it’s really shocking. It was a big scare. It reminded me how fast life is and how it can be over so quickly. My uncle has had two heart attacks too. He’s alive and well, but it was another wake-up call that heart disease can strike anyone at any time. To be able to help people like my uncle or my best friend is what drives me. I knew I could use my skills in research to do some good.
Setting up a new lab
My aim at the beginning of my post-doc in Oxford was to simply establish zebrafish as a model system. When starting a new project from scratch, there’s no expertise to guide you.
I needed to take the lead.
So I travelled to Spain with my (heavily pregnant!) colleague (BHF-funded post-doc research fellow Filipa Simoes) to train in a lab there and learn how to carry out heart microsurgery. My next challenge was to investigate the equipment needed, expand the aquarium, and raise hundreds and hundreds of zebrafish. It was a long process, but an exciting one.
To look at specific cell types and how they move through the body over time, we developed transgenic fish, where fluorescently-labelled genes are inserted into the fish’s DNA. When the labelled gene is switched on, specific cells light up blue, red, green, yellow, or any colour of your choice! It’s the perfect way to see with the naked eye where particular cells are, and which genes are linked to the cell.
We then breed the transgenic fish, so when they lay eggs their offspring will also be transgenic and have the ability to light up specific colours if a gene is present and working.
We started to label lots of different cell types in a single zebrafish — the blood vessels, the lining of the heart, cells of the blood. This creates multi-coloured fish which are not only beautiful, but allow us to ask all sorts of exciting questions such as — how are fish able to repair their hearts? And what genes are involved?
Teamwork is everything
Now, there are two female students and three female senior post-docs (Filipa, Mathilda Mommersteeg and I) working with zebrafish here in Oxford. We call ourselves — the five fish girls!
We work as a team. We all stimulate each other’s minds and challenge each other to look at the bigger picture. Two big things we are looking at are epigenetics, where we’re looking at the effects of specific genes being switched on and off, and the cell cycle in heart muscle cells — the process by which they divide and reproduce, allowing the fish to regenerate.
Working alongside my colleague Filipa, we are breeding fish and looking at genes whose activities change during repair. We then look at the cell cycle in that fish and look at which cells are able to re-enter the cell cycle and which factors are needed to do so, with the hope of triggering these responses in non-regenerative hearts. This will be a long process, but we’re determined.
We’re also working with BHF Professor Paul Riley…
Paul’s lab looks at how mice repair their hearts. The cardiac repair process in mice happens only when the mice are new born, but fish can repair their hearts throughout their whole life. By comparing our models we can ask all sorts of questions: are the repair processes the same? Why do fish continue to repair their hearts throughout life and mice do not?
It’s a tremendous opportunity, working in Oxford. I’ve never found a place that offers this much support in research. There are so many brilliant people here. If you need something, within a few days you have it or you know how to do it. I love working here.
If you can’t do it here in Oxford — I don’t know where you could.
The drive to keep going
Working in cardiovascular research can be tedious at times and pressurised. But I find I don’t want to do anything else. My work is so rewarding. I believe zebrafish research is really close to producing some answers that could be applicable to real people.
Oxford has become my home, in part due to my work and my colleagues, but also due to my partner. I met Markus Toegel when I was studying in Vienna. We were long distance for ten years before we both moved to Oxford. He’s also a scientist here.
He works with flies, trying to find new ways of highlighting different genes to see where they are switched on, and what processes they are involved in.
Life outside the lab
I love my work, but it’s good to escape the lab now and again. When I studied in London, I lived behind the Tate Modern and used to go there all the time. London was hustling and bustling — it was infectious. But now I’m in Oxford, I love the space.
I found a lovely little English cottage with a garden. It’s 260 years old and I am completely in love with it. I love pottering around in my garden, seeing to my roses, and growing my own vegetables.
When it comes to my research, I love what I do. I hope one day my work can help improve the future of people affected by heart disease.
Until that day arrives, I’ll keep working hard.
Find out more about BHF-funded regenerative medicine research.
