Generating GABAergic interneurons: a PhD Interview with Andreas Bruzelius
Andreas Bruzelius, a Ph.D. student at Lund University, defended his PhD thesis on Friday, 20 October 2023. Andreas' research focuses on generating brain cells, specifically interneurons, in the lab, which has significant implications for the study of neurodegenerative and neuropsychiatric disorders. Combining cell biology and electrophysiology, his work has the potential to create personalized disease models for future research.
In this interview, Andreas discusses his research journey, his aspirations for the future, and his experience as a Ph.D. student.
What have your Ph.D. studies focused on?
"During my time as a Ph.D. student, my research has focused on GABAergic interneurons. Interneurons are a specific type of neuron. Interneurons are the central nodes of neural circuits, enabling communication between sensory or motor neurons and the central nervous system. They also contribute to higher brain functions like learning, memory, cognition, and planning. Several neurodegenerative and neuropsychiatric disorders including autism, schizophrenia, and epilepsy, may be caused by damage to interneurons.
I've worked specifically with generating interneurons in the lab, using reprogramming and differentiation strategies. The focus has been on GABAergic interneurons and making them from different starting cells.
One way we did this was by converting adult fibroblasts, or skin cells, into interneurons. In this case, the purpose was disease modeling of late-onset neurodegenerative diseases. Using this type of direct conversion approach rather than making them from induced pluripotent stem cells, where they revert into a naïve state, helps to retain the epigenetic age of the patient in the generated interneurons. So, if you have a late-onset neurodegenerative disease that you are studying, you can model this more easily using direct conversion.
I've also worked with differentiation from embryonic stem cells into interneurons. Here, we created a robust protocol that can be used later on for disease modeling of developmental or more early-onset brain disorders," explains Andreas Bruzelius.
Can you tell us about the cover of your thesis?
"The cover of my thesis represents my four years and the cells I grew during this time. It symbolizes how the cells grew, as I grew as a PhD student.
I had this plan of making an orchard of neurons, where they grow as trees in the end, and I wanted something that also symbolize the flow of time as well. So, I spoke to a friend who is an artist and he helped put it together, I just conceptualized it. He didn't know what a neuron was, for example, so there was some explaining about them and showing pictures, etc. In the end, he put everything together perfectly" reflects Andreas Bruzelius.
How did you end up doing a Ph.D. at Lund Stem Cell Center?
“I'm from the east coast of Skåne, from a town called Kristianstad. I grew up a little outside the town and spent a lot of time in the forest around there. I've always been interested in science, my grandmother used to show me a lot of animals in the forest, we looked at snails laying eggs, tadpoles becoming frogs, and those sorts of things.
So, I've always been very curious about things and got more into the molecular side of science later. I started with what we call here in Sweden, green biology, which focuses on plants and fauna, for example. I came to Lund in 2011 to study languages and then I ended up doing a double bachelor's in molecular and green biology here as well. After that, I continued with the master's program in molecular biology here at Lund University.
Before I started studying in Lund, I didn't know that research was a job that people had. I didn't know a PhD was even something that existed. When I started my bachelor's, I realized that this was something I could pursue, and it was during this time that I realized that research is something that I like to do and something I wanted to pursue in the future.
Then as I was doing my master's, I realized that I wanted to be in neuroscience and that I wanted to stay in Lund, which is quite a competitive thing. Then through different strokes of luck, Daniella Ottosson had a position open. I applied and was able to join her research group as a PhD student. That's how I ended up here at BMC.
Daniella has been the perfect supervisor for me, and I think I have been a good first Ph.D. student for her. So, it has worked out great” notes Andreas Bruzelius.
What have you found the most enjoyable during your Ph.D. studies?
“I think the PhD has gone how I expected it. It’s been a very nice experience, I had amazing supervisors and great collaborators. It has been more of a marathon than a sprint. Maybe, I wasn't totally read up on how to pace myself, but you get so much help from your friends in this, which made it was more than fine. I think that it’s the people around you that really make the PhD what it is. They don't necessarily need to be in your lab, it’s the other PhD students that you interact with and become friends with that really are the glue that holds you together.
The science has also been incredible. I like doing research here in Lund, we have a very open and collaborative environment. I also like to figure out how things work and to watch something start very small and follow it for a long time. I think that's why I enjoy the neuro field so much, it's like laying a puzzle where the pieces are not known yet. I especially like cell culture, the type of cell culture I do is often over a long period of time so, I can see how the cells grow, how they develop, and how they change. This is what I love about the in vitro work that I do.
During my PhD, I also learned about patch-clamp electrophysiology and I’ve loved it. When you patch a cell, you get instant results, and know immediately if you have a neuron or not based on the function of it. Neurons are the only cells in our body that fire in that sense. Cardiomyocytes can also fire action potentials, but it looks completely different and it's such an absolute that no one can really argue against it. If I say it's a neuron, it's a neuron.
I’ve really enjoyed being a bridge between electrophysiology and cell biology. I could comprehend both methods and incorporate them into my PhD and used them efficiently. This also opened the door for a lot of collaborations, because it's not always that electrophysiologists are cell biologists, and vice versa. So just being a bridge between this, I could see how to improve the culturing methods to get a better readout in the electrophysiology, which has been very rewarding during my PhD.
But in many ways, I think the most enjoyable aspect has been the people that I have met. Those I’ve met along the way have really shaped the kind of scientist I am and how I approach my own research questions,” highlights Andreas Bruzelius.
What has been the most challenging aspect?
“I think the most challenging is to avoid getting tunnel vision. Sometimes you need to know when to let go of something, and I think my supervisor has been great there. She has really helped me realize when we should move to the next step, because I can easily snowball into something and then dig into the finest details and keep going. So, knowing or realizing when it’s time to step back, has been one of the harder aspects.
Then also seeing people leave, that can sometimes be hard, it's a bittersweet thing because you see people leave and you’re happy for them, and new people come. It’s just part of the environment,” says Andreas Buzelius.
What are your plans following your Ph.D. defense?
“Following the PhD defense, I am contracted until December in the Ottosson Lab. So, I will stay until December and then I’ll look for a postdoctoral position. I would prefer to stay here at the BMC and in Lund if possible, so hopefully I can manage to find a position here that is also in the neuro world. That would be amazing.
Any tips or advice for future Ph.D. students?
“First of all, make sure you want to do this. Make sure you want to do a PhD; it will cost you time. Make sure you have a good support system in place, you will need it, the PhD life goes up and down. Also, don't just judge an experiment because it goes bad. Take time. Think about why it went bad and try to improve.
Lastly, I want to end with one piece of advice I received when starting that I found very valuable - think about every experiment as a figure in your paper. It will help you visualize why you do the experiment and think to yourself, what is the question I want to answer with this?” concludes Andreas Bruzelius.
Email: andreas [dot] bruzelius [at] med [dot] lu [dot] se (Andreas[dot]Bruzelius[at]med[dot]lu[dot]se)
Associate Senior Lecturer
Wallenberg Academy Fellow
Email: daniella [dot] ottosson [at] med [dot] lu [dot] se (Daniella[dot]Ottosson[at]med[dot]lu[dot]se)
Ph.D. Defense Details:
Andreas Bruzelius defended his Ph.D. thesis “Generating GABAergic interneurons through reprogramming and differentiation strategies” on Friday, October 20th at 9:00 in Segerfalksalen, BMC A10.
- The opponent is Dr Lynette Lim, Leuven
- The chairman of the dissertation is Professor Merab Kokaia
To find out more about the event and save the date please visit our calendar.
Read the full Ph.D. thesis in the Lund University Research Portal.