Martin Loose studied chemistry at the University of Heidelberg, Germany. He then joined Petra Schwille's group at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, where he obtained his PhD degree in 2010 for work on self-organization and pattern formation in the bacterial Min protein system. He then moved to Tim Mitchison's lab at Harvard Medical School, Boston, USA for his postdoc, funded by Human Frontier Science Program (HSFP) and European Molecular Biology Organization (EMBO) long-term fellowships; there, he discovered that the bacterial cell division proteins FtsA and FtsZ self-organize into dynamic cytoskeletal patterns. Martin established his independent research group at the Institute of Science and Technology (IST) Austria in 2015, supported by an European Research Council (ERC) starting grant and HFSP Young Investigator Grant. His lab studies the self-organization of bacterial cell division and small GTPase networks.
What inspired you to become a scientist?
I've always been interested in science, and was also encouraged by my parents. My mother used to be a technician at a Max Planck Institute close to Munich, working with Konrad Lorenz, who won the Nobel Prize at the time. She loved to tell stories about the scientific community and working in the lab, and she also taught me to be curious. We had lots of scientific books and magazines that I liked to look at, even before I could read them. Also, I was about 12 when the movie Jurassic Park came out, and I thought the idea to clone a dinosaur was just amazing. Later, I started reading textbooks, which were probably still too high-level for me, to learn about things like molecular biology. But then during high school, I got interested in chemistry, which is what I studied for my undergrad.
So, how did you then get back to biology?
I actually wanted to do biochemistry, but there were not many universities offering this as a subject and the one I applied to didn't take me. While studying chemistry in Heidelberg, I did take extra biology classes on the side and became interested in mechanisms in living systems. But I actually also really enjoyed my chemistry studies; there was a strong focus on designing catalysts to control chemical reactions and it was fascinating to learn how you can really tune molecules so that you get only one product and nothing else. Then, towards the end of my studies I heard a talk from François Nédélec about the self-organization of mitotic spindles, and I just loved the topic so I asked if I could do my Master's thesis with him.
And you've been working on self-organization ever since. Could you tell us about the main questions your group is trying to answer just now?
One of the main interests of the lab is trying to understand bacterial cell division by using in vitro reconstitution approaches – and we now know the 12 essential proteins that have to come together to form a dynamic complex and divide the cell, so we are now increasing the complexity of the reconstituted system to include more proteins, also in different membrane geometries. During my postdoc, I saw that filaments of FtsZ – the bacterial homologue of tubulin – treadmill, and since then it became clear that this behavior is important for cell wall synthesis. So, we are trying to rebuild the system to understand the coupling between treadmilling filaments and peptidoglycan synthesis. Since I arrived here at the Institute of Science and Technology (IST), the other main topic we've been working on is regulatory networks of small GTPases. Here, the idea is to understand how nonlinear interactions between GTPases and their regulators on a membrane surface establish the biochemical identity of organelles in eukaryotic cells. I think by having reconstituted the activation network that controls Rab5, we have a good starting point to increase the complexity in this minimal system and reconstitute Rab GTPase conversion and cascades, as well as understand where spatial-temporal order comes from, because this eventually gives rise to compartmentalization of a living cell.
Looking a bit into the future, what kind of biological systems will we be able to reconstitute in say 5 years’ time?
In reconstitution approaches, you always start with identifying the minimum number of components that you need for a specific function, which we like to describe as modules. Of course, if you want to reconstitute something complex like cell division, you need many different modules interacting in a super-module with each other. But with each added component, the complexity increases exponentially. So, I think what you eventually need is a multi-lab collaboration where each group focuses on an individual module and then in the end they put it all together. There are many great labs reconstituting different aspects of cell division, cell polarization, cell motility and chromosome organization, so I wonder if it would makes sense to at some point put it all together and have full control over a minimal cell, although I doubt that 5 years would be enough for this. But what I'd emphasize here is that even if you define long-term aims such as reconstituting cell division, when you start step-by-step there are already so many interesting things you learn along the way.
“[…]even if you define long-term aims such as reconstituting cell division, when you start step-by-step there are already so many interesting things you learn along the way.”
Are there any novel technologies you are particularly excited about?
I'm really excited about what's possible with cryo-EM! Here at IST, we have great facilities and colleagues like Florian Schur, Carrie Bernecky and Leo Sazanov, and there's a lot of knowledge on campus. We have some projects where we're hoping to make use of cryo-EM to better understand the molecular mechanisms underlying the mesoscopic behavior we see in our fluorescence microscopy experiments.
Let's go back to the time when you started your lab. What were the things you found the most challenging as a new PI?
There is the ‘loneliness of the PI’ that people talk about and you indeed are quite on your own; this is also a challenge because you have to make a lot of decisions and often there isn't anyone to directly talk to. In contrast to your postdoc, where you mostly focus on one main thing that you are an expert at, there are suddenly a million other things you have to do that you aren't experienced in, and these include managing people, resolving conflicts and encouraging people when they feel frustrated. Luckily, IST is a growing institution and there are several new PIs every year, so I had a pretty good peer group with five other assistant professors who started around the same time as me. I would recommend to anyone who is starting a lab to reach out to people who are in a similar situation, because the problems you face are often the same and it really helps to just talk about them.
How have your previous mentors influenced you in the way that you run your lab?
Both my PhD mentor [Petra Schwille] and postdoc mentor [Tim Mitchison] really enabled people to follow their own interests and develop their own scientific identity, all while providing an environment where you could just play around with things. There was never really pressure and it was all about finding something exciting, working hard for it, but also having fun. I think this playful approach to science is good and I've tried to establish that in my lab too, so that people really come in and enjoy doing the experiments.
“I think this playful approach to science is good and I've tried to establish that in my lab too, so that people really come in and enjoy doing the experiments.”
Is there any piece of scientific advice that has stuck with you?
I really like Uri Alon's TED talk on the ‘cloud’, which is the phase when you get stuck in your project, and I encourage all my students to watch it. You have to appreciate the state of being lost and trying to find a way out with exploration. You'll always find something interesting, even if it is different to what you were expecting to see – that's just how science works. Realizing this can make people feel more optimistic and confident that things will be okay. Especially at the beginning of my PhD, I got extremely worried when things were not working out and if I didn't know what to do as a next step; looking back, that worrying was unnecessary. You have to stay positive, otherwise you can't really enjoy the process.
You were an organizer of a session at the Cell Bio Virtual 2021 meeting. How did you experience the meeting and what formats do you think conferences will have in the future?
An important part of the annual Cell Bio conference is meeting up with everyone you've gotten to know during your scientific career, so it's a bit sad that we weren't able to do this – Tim [Mitchison] actually always organizes alumni dinners at this conference, which of course didn't happen this year. You can still have good scientific discussions at online conferences, but the social part and random encounters that are important in science are gone, so I really hope the next ASCB will happen in person. Going forward, I think there will still be some purely online conferences, some in-person-only meetings, and also some hybrid meetings. I will actually be putting in an application for organizing an EMBO Workshop with Ana-Maria Lennon Duménil and we'll probably go with some form of hybrid meeting; it's important to be able to reduce travel and make the conference more accessible to those who wouldn't be able to attend in person. But how to go about online participation and how to provide some kind of confidential environment for discussing unpublished data are things we've been thinking about quite a bit. I'm looking forward to seeing what kind of solutions other people come up with in this regard.
And what are you looking forward to in 2022?
I would just like some form of normality again. My daughter is starting school and I really hope she won't have to start with home-schooling. 2021 was strange because we were all waiting for the pandemic to end and life to go back to normal, but that of course didn't happen. Other than that, I'm really excited to get some new people in the lab, and I'm really itching to start some new projects and see what we can reconstitute.
How do you juggle being a good scientist and a good parent?
You always try to be the best possible boss, scientist and parent, but it's hard to be the best at everything at the same time. It helps that as a PI I am quite flexible with my schedule – I can pick up my children from kindergarten at 4pm and then continue working late after bringing them to bed. This would be more difficult to do in many jobs outside of academia that have fixed working hours. I also benefit from the infrastructure at IST because they have their own kindergarten on campus.
Finally, could you tell us an interesting fact about yourself that we wouldn't find on your CV?
Probably not many people know that I used to be a local hip hop celebrity in the little town I grew up in [smiles]. During high school I was a rapper in a hip hop band and I think we were pretty good. We had lots of concerts on the weekends and took part in a national competition, where we were invited to go to Berlin; ‘Smudo’ from the band ‘Die Fantastischen Vier’ was in the jury and we had a chance to talk with him, so that was fun. I still listen to hip hop, especially if I need the energy to power through to meet a grant deadline.
Martin Loose's contact details: Institute of Science and Technology Austria (IST Austria), Lab Building East, Am Campus 1, 3400 Klosterneuburg, Austria.
Martin Loose was interviewed by Máté Pálfy, Features & Reviews Editor at Journal of Cell Science. This piece has been edited and condensed with approval from the interviewee.