“I appreciate having a deeper understanding of how the body works.”
Olivia Sveidahl Johansen is a Danish PhD student in the Gerhart-Hines group at CBMR. She joined the group as a student assistant in 2015 and was recently first author on a paper in Cell describing how the receptor GPR3 on the surface of brown fat cells drives calorie-burning without the need for an external signaling molecule. Having explored GPR3’s functional role for her master’s thesis, Olivia is now pursuing a PhD to determine the transcriptional machinery responsible for GPR3 regulation.
Why is the discovery of GPR3 so significant?
"It opens new doors for treating obesity. To combat obesity, you can do one of two things, roughly speaking. You can increase your calorie burning or you can decrease your caloric intake. One promising approach would be to boost calorie-burning along with food intake reduction in order to create an even greater negative energy balance. Available treatment strategies suppress caloric intake by modulating appetite, but to this day we haven’t safely managed to activate calorie-burning in humans. Here, the brown fat tissue holds exciting potential because of its energy-expending capacity and GPR3 poses a potential new strategy because it opens the door for gene therapeutic approaches, which would be very different from classical pharmaceuticals."
Where did your interest in science come from?
"As a kid, I always had different projects going on and I’m very curious. For me, most answers just raise more questions. Once I learn something, I want to know more. I’m not the type of person who knows a little bit about everything. I'm the type of person who enjoys knowing everything about a more specialized topic."
What did you study at university and why?
"At first, I was interested in medicine and considered becoming a doctor because I wanted to improve people’s quality of life and to do something meaningful. But I’m much more driven by long-term projects where you have something you want to understand and keep asking questions. That’s more fulfilling to me. So, I ended up studying Molecular Biomedicine at University of Copenhagen. It’s a degree for people who are interested in medicine from a research perspective – rather than medical practice. Here, I am ultimately still able to help people while continuously asking targeted questions into the underpinnings of health and disease."
Eventually, you specialized in metabolism. Why?
"What makes it so fascinating is that it's a field that everyone can relate to. More and more people are diagnosed with metabolic diseases, and I had all these questions. Like, what’s going on? It cannot be simple. There must be more to it than telling people to eat carrots and go for a jog. It’s more complex. I enjoy the fact that metabolism is a very dynamic phenomenon. If you do something to one component, it’s going to affect another – the entire organism is at play here. More specifically, I work with brown fat, and I am driven by the overarching goal to unlock the therapeutic potential of an organ that we know has such high calorie-burning capacity. I like the fact that the brown fat field is relatively young. It creates a very vibrant atmosphere, where there's a lot to be discovered."
Olivia Sveidahl Johansen discusses the discovery of GPR3 in the video, above.
What are you hoping to discover through your research?
"Within cell surface receptor research, most focus has been on the more traditional means of receptor activation, where an external molecule — or ligand — binds to the cell surface receptor in order to promote signaling within the cell. Less understood is the role and regulation of the so-called constitutively active receptors, like GPR3, which signal independently of an external ligand. One could ask why constitutively active receptors like GPR3 evolved at all. Why do these two types of receptors exist — the ones that require a ligand to signal and the ones that don’t — and how do they interact? I am inspired by these curiosities in my PhD project, where I am investigating the molecular machinery within the cells that regulate the levels of GPR3."
How did you come to be at CBMR?
"I took courses on metabolism as part of my undergraduate degree and had all these questions accumulating in my head. I decided to send an application for a job as a student assistant at CBMR. In fact, I sent it to Torben Klein [CBMR’s former director] because I thought he must know a lot about metabolism. Fortunately, he sent my application to all of the research leaders in the center and Zach [Gerhart-Hines] had an open position. We had a very fruitful collaboration, which turned into a master’s project and now a PhD."
What’s it like working at CBMR?
"The collaborative nature of the center is very strong. Here are so many different people doing different types of research that overlap because we all have this shared interest in metabolism. We have frequent presentations and meetings across the groups and very often a presentation will seed new collaborations because you become aware of some interesting research that another group is doing. In fact, Zach presented the work I’d been doing on GPR3 at one of these meetings at a very early state of the project and Group Leader Brice Emanuelli, who works on the floor above, immediately recognized that his lab was experienced in a special method that would be interesting to test with our target. A new project was born. Had Zach not done that presentation, had Brice not reached out after the meeting, I would never have realized how much potential his method had to help me answer questions relevant to my project."
Has your research influenced how you live your own life?
"It would be a lie if I said it took five years of studying metabolism to know that the mind and body are completely intertwined and that it's good to have an active lifestyle and a balanced diet. I think my body communicated that message clearly before I even opened a book. But I appreciate having a deeper understanding of how the body works."
Finally, where do you see your research career going?
"Right now, I enjoy working in academia. What I appreciate about it is the very short distance from idea to execution. We often have fruitful meetings discussing data and developing hypotheses, and the fact that I can go straight into a lab and test these ideas afterwards is very stimulating to me. In that sense, I think that academia is the ideal place for a person like me who’s driven by the treasure hunt of science. I have a long career ahead of me and want to do research abroad one day, but right now I’ll focus on my PhD project and stay open-minded."
Interview by James Clasper. Edited for clarity and concision.