Tim Lämmermann studied molecular medicine at the Friedrich-Alexander-University, Erlangen-Nuremberg, Germany and the Lund University, Sweden. He then joined the lab of Michael Sixt at the Max Planck Institute of Biochemistry in Martinsried, where he earned his PhD in 2009 for studying the role of integrins and cytoskeletal forces in immune cell migration. Tim then moved to the National Institute of Allergy and Infectious Diseases in Bethesda, USA for his postdoc with Ron Germain. There, he worked on the mechanisms of neutrophil swarming during infection, and received the Robert-Koch Postdoctoral Award in 2014. Since 2015, Tim has been a Group Leader at the Max Planck Institute of Immunobiology and Epigenetics in Freiburg, where his lab investigates the single-cell and population dynamics of immune cells. He was awarded an ERC Starting Grant in 2016.
What inspired you to become a scientist?
As a kid I liked watching a lot of TV about wildlife and nature – you know, when David Attenborough suddenly shows up behind a cliff and says “Look at this little seashell” with his distinctive voice, that's really captivating. I think my interest in immunology started later as a teenager. I often had tonsillitis with abscesses and got super frustrated when the doctor told me that I couldn't do sports until the white stuff was gone. I of course became curious about that white stuff in my throat – was it bacteria the doctor was talking about, or were those the immune cells? And why did I have to take antibiotics even after the white stuff was gone? So, I think that's where it started, but then the real decision to work on immune cells came during my Master's, where for 6 months I was staring through a microscope and looking at spleen sections, which is a very boring task per se. But for me, it felt like entering a new little universe with so many questions. And I really started to devour the literature on immune cells, which included getting copies of some papers from the 70s from the library; maybe you could call it ‘binge reading’, as it just didn't feel like an effort. Now, in my lab, we're making movies of immune cells, which is fascinating – so I might sometimes suddenly step behind a microscope to tell a student “Look at this neutrophil!” (but not quite with a David Attenborough voice).
Could you tell us a bit more about the questions your lab is trying to answer?
We are studying the single-cell and population dynamics of immune cells, mainly focussing on the adaptive immune system. On the one hand, we are looking at very fast migrating neutrophils to try to understand the principles of their self-organization and swarming behaviour. On the other hand, we have also started to look into tissue-resident immune cells, which stand on the other side of the migration spectrum and are rather slow. Here, we are addressing the role of cell adhesion and cytoskeleton coordination in the formation of tissue-resident networks, focussing on macrophages and mast cells. And what we have also started to do, in collaboration with the research group of my wife, Angelika Rambold, is assess how organelle dynamics and metabolism in these two cell types influence these networks. We have a very exciting hybrid project on how different immune cell populations communicate with each other – this started with an observation using intravital microscopy where we saw unexpected and unconventional crosstalk between mast cells and neutrophils.
How did you get into imaging cells with intravital microscopy? And has this method been key for understanding the migration and dynamics of immune cells in your work?
During my PhD, I worked with collagen gels and discovered that immune cells use completely different modes of migration in a 3D environment compared to when they are in a regular cell culture dish. After submitting this work, all three reviewers commented that it's nice that we show this in collagen gels, but is this how it really works in the tissue? At the time, intravital two-photon microscopy was still a pretty new technique, so we teamed up with Reinhold Förster in Hannover; I was really sweating that our findings in collagen gels remain true in vivo, otherwise the whole story would fall apart. Afterwards, upon joining Ron Germain's lab for my postdoc – which was also a personal decision as my partner had a position lined up at the NIH – I had the chance to do research the other way around and first look into the tissue with intravital microscopy and then dissect any interesting observations. So this is when I first saw neutrophil swarms under the microscope, and, since then, this technique has been absolutely key for me to observe and understand what's happening with immune cells in heterogeneous and complex tissues. What's fascinating about immune cells is that they're very plastic and can adapt their behaviour. For example, if they can't move through a narrow pore, they'll take the next one that's a bit wider; or if you interfere with cell protrusiveness, immune cells might just switch to another contractile mode and migrate. And thinking about the immune response, there are even more compensation mechanisms that come into play, such as the recruitment of neutrophils if a macrophage can't get the job done. All of these things can't be captured in reductionist in vitro systems.
“What's fascinating about immune cells is that they're very plastic and can adapt their behaviour.”
Tim with his daughter: directed movement or random motility?
It does seem like a big challenge to understand this complexity…
When I applied for my current position and talked to the directors and group leaders about my plans to study this level of complexity of immune cells in tissues, one of them actually said “But this will kill you!”.
What challenges did you face when starting your own lab that you didn't expect?
I did my PhD in Germany, then went to the US for my postdoc, and when I came back I kind of had a reverse culture shock. In a way, I was looking forward to the typical German cliché that everything is much more organized here. But what I did not expect is how much bureaucracy I have to deal with as an independent group leader. In the beginning, this was a real challenge that I wasn't trained for. From justifications for work contracts and lab equipment to lab safety documentation for bacteria and gene-modified organisms, just to name a few. There are more and more forms coming my way, so I spend a substantial amount of time dealing with these things, which slows me down and takes time from supervising the actual science.
What is the most important advice you would give to someone about to start their own lab?
Stay true to yourself and believe in yourself – and also don't compare yourself with others! When you are a new group leader, you will get advice from many people, which is often helpful, but it's important to remember that everybody had their own path and story. So you should not panic if your path goes slightly differently. There will always be a PI who had their first senior author paper earlier than you, or someone who managed to get their first big funding faster than you.
“Stay true to yourself and believe in yourself - and also don't compare yourself with others!”
And what was the best piece of scientific advice you've ever received?
This was when an NIH Director told me to think big at the beginning of the project. And the rationale behind this is that small papers are almost as much work as the big ones – certainly when it comes to manuscript preparation. As a junior group leader, I would maybe amend that and say think big, but also be realistic about what your students can achieve.
You mentioned that your wife is also a group leader. How do you achieve work–life balance when you're trying to establish yourself as an independent investigator?
The ‘life’ part starts when we pick up our daughter from kindergarten, and she completely immerses us into her life. Then when she goes to bed, work starts again – which is important if you want to be in a good situation for getting the next position, and both my wife and I currently have non-tenure-track positions. After midnight, when everyone's asleep, I sometimes listen to some electronic chill music and it's when I have my best ideas. I know this doesn't really sound like the number one recommendation you'd get from a work–life balance book, but again, other people will find different solutions and it doesn't make much sense to compare them.
Finally, could you tell us an interesting fact about yourself that people wouldn't know by looking at your CV?
I still try to play in a competitive men's tennis team, but I have to say it's more and more of a challenge to find enough time to keep fit and to keep up with my teammates. What also keeps me busy is our daughter, who just loves to replay all her favourite audiobooks. So I've become an expert in inventing crossover stories from Petronella Applewitch through PAW Patrol to PJ Masks – if you want to know more about these characters you can just call me (smiles).
Tim Lämmermann 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.