Ersi Christodoulou on understanding the formation of bile ducts in the embryo

She talks about the bile ducts, tubular structures that carry bile (a fluid involved in digestion) from the liver to the intestine, and how science usually leads where it wants to go, regardless of the original hypothesis, and how she transported a plate of bile duct organoids on a train from Edinburgh to Dundee.

Ersi studied Natural Sciences for her bachelor's degree at the University of Cambridge, where she specialised in genetics in her final year. Her thesis and many of her internships focused on developmental biology, a topic she also chose for her doctoral dissertation.

She is a first-year doctoral student in Luke Boulter's lab, beginning a project on how the interplay of molecular players and tissue mechanics contributes to the formation of bile ducts in the liver. These tube-like structures are important for transporting bile from the liver to our digestive system. To study this, she uses a range of mouse models and in vitro systems, as well as various techniques including microscopy, molecular biology, and proteomics.

Could you briefly summarise your work?

My main interest is developmental biology and how structures form in the body during embryonic development. The system I focus on is the liver and in particular the bile ducts. These are tubular structures that transport bile (a fluid involved in digestion) from the liver to the intestine. To understand how bile ducts form in the embryo, I focus on the interplay between molecular players and tissue mechanics and how this gives rise to 3D structures.

Why is your research important? How is it relevant to people's lives?

Much of the biological and medical research focuses on diseases and their causes. This helps in disease prevention and drug development. However, to understand what is going wrong, we need to know what "right" looks like. This is where development comes in. If we understand the fundamental processes that help create structures that lead to functional systems in the body, then we can understand how these processes are deregulated during disease. Bile duct diseases, also known as cholangiopathies, include cholangiocarcinomas, biliary atresia, and biliary fibrosis amongst others. Evidence suggests that many of the pathways involved in these conditions are actually pathways that were previously necessary for the development and formation of the biliary tubes. Hence, understanding these pathways is of particular medical importance.

What are the major challenges in your field?

Developmental biology is a particularly challenging and complex field. Within 21 days, a fertilised mouse egg transforms into a newborn mouse. Thus, within 21 days, a fully functional organism has emerged from a cell. To achieve this, many events must be coordinated spatiotemporally, with a large number of pathways and players feeding into each other, influencing and regulating each other. This makes development particularly complex, mostly allowing us to make associations between genetic players and processes, but rarely alllowing us to form concrete causative links. This means that we can know that bile ducts don't form when we deregulate X, but we don't know how exactly X does this, since X is a complicated protein that communicates with many other molecular players and has more than one role.

What inspired you to be a scientist?

Unfortunately, my response to this is not particularly exciting or inspiring. For as long as I can remember, I was always terribly bored by everything I was taught, except for science. That was the only time during my school years that I can remember being engaged and mentally present. Over the years, I became fascinated with the idea that there is much more to science than what the eye could see, and how all of these complex and fascinating organisms, processes, and systems simply boil down to a handful of molecules.

What do you like best about your job? What do you like the least?

It's a very flexible job, both in terms of the hours you work and the direction you want to take. Usually the science takes you where it wants to go, regardless of your original hypothesis (as anyone who has done a PhD knows), and that is quite fun. On the other hand, the uncooperative nature of science is not fun when you come to work at 9 a.m. and find that your experiment has failed yet again. It's often hard to pick your battles and know when to insist, but also when to move on.

If you could have tea with another scientist (alive or dead), who would it be? What would you talk about?

With no doubt it has to be Lewis Wolpert, a developmental biologist mostly known for his French flag model in morphogenesis. This model provides an explanation as to how cells know where they are in the tissue and what kind of role they need to play to aid in forming an organ correctly. I remember reading his book “How We Live And Why We Die: The Secret Lives of Cells” as a teenager thinking how can someone communicate such complex biological concepts in such a simple and elegant way, while also making the occasional joke. He simply sounded like someone you want to have a coffee with.

While I also decided to follow developmental biology, I would rather pick his brain about various topics that he has often touched upon in his interviews, particularly the ethics of science. Are there questions we shouldn’t ask, is it a scientist’s responsibility to judge what is ethically correct to study and should research be stopped when it comes to knowledge that could be weaponised or used inappropriately?

As Wolpert has said: “What you do with it (scientific knowledge) is another matter. I always say that you don’t need science to do terrible things. It’s what you do with your knowledge that matters and I claim that science is ethics- and value-free. It’s the way the world is.”

What is the most unusual thing you have done as a scientist?

I have not been a scientist long, so maybe in a few years I'll have a better story, but for now I'd say I carried a plate of bile duct organoids on a train from Edinburgh to Dundee. I had to use a special microscope that is only available at the Dundee Imaging Facility, and there was no way to ship our organoids there, so I casually took my train ticket, my phone, and a plate of organoids on a field trip. Good thing no one asked any questions.

If you weren’t a scientist, what would you be doing?

I would have channelled my inner Mary Fiore (Wedding Planner, 2001- great movie) and become a wedding planner. There is no better feeling than ticking things off a long list. And what better tasks to have than flowers, cakes, catering and wedding dresses. Probably better than qPCRs, stainings, dissections and tissue culture.

Do you have any advice for people who want to go into this field of research or start a career as a scientist?

I would say that you should realise how unpredictable and uncooperative biology is. Unfortunately, we are not told in school and university how hard research is. There are constant disappointments and it takes a lot of perseverance to do the same thing every day until it works out. On the other hand, it also gives you a lot more satisfaction when something is successful. Just remember that it's not always our fault, it's mostly biology's fault (at least that's what I tell myself).

What do you think are the major challenges facing humanity? How can science help?

From poverty to war, climate change, fresh water shortages, disease, human rights, and aging populations, the list is unfortunately very long. These problems have plagued humanity for as long as we can remember, and history tends to repeat itself. The only way to break the cycle is for us to know more and act better than we did before. Science is expanding our knowledge and understanding of things on a daily basis, and we can apply that knowledge to many of the challenges mentioned above. However, science alone is not enough. Knowing the truth is not enough. It is how you apply that knowledge that matters, and unfortunately, that is not in the hands of scientists, but in the hands of governments. So can science help? Yes. But can it tackle humanitarian crises alone? No.