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Probing bacterial injection needles at nanoscale



Heidelberg, 16 May 2018 – Marek Basler, one of two recipients of the EMBO Gold Medal 2018, talks about his work on bacterial type VI secretion systems, his fascination with molecular machines and the joy of discovering something new.



What led you to working on bacterial secretion systems?


I’ve been interested in bacterial pathogenesis since I started research as a Master’s student. The sorts of questions I ask and how I answer them have changed, but the topic didn’t change that much.


I worked on my Master’s thesis in Peter Šebo’s lab [at the Institute of Microbiology, Prague, Czech Republic], where I also stayed for my PhD. That’s when I became interested in bacterial pathogenesis and the toxins bacteria produce to manipulate host cells.


I met my postdoctoral supervisor, John Mekalanos [Harvard Medical School, Boston, USA] at a conference. He gave a talk about bacterial type VI secretion systems. I was fascinated by this machine that had just been discovered, and wanted to know how it works. So that was how I chose his lab. It was a sort of progression of the research I had already done.


What is the focus of your research now?


My lab investigates how bacterial cells interact with their environment. We study how some bacteria use the type VI secretion system to deliver toxins across membranes of other cells to kill them or manipulate their behavior.


The type VI secretion system is a large, dynamic nanomachine that works like a speargun. We want to know how this machine is assembled, how the assembly is regulated and which factors it secretes. We also look at how the secretion system varies between bacteria.


And which techniques do you apply to these questions?


I really like to see how things work. During my postdoc we collaborated with Grant Jensen’s lab [at the California Institute of Technology, Pasadena, USA] to use cryo-electron tomography to visualize the secretion system inside bacteria. When we saw that it was a very large complex, we realized we could use fluorescence microscopy to study it.


We now know it’s possible to tag lots of the components and visualize their assembly in real time within cells. In my lab we do live-cell imaging to look at the dynamics, but I also have specialists in electron microscopy, who study structures of components of this machine. We then combine all this information.


In general, which scientific questions fascinate you?


I’m particularly interested in molecular machines: how they carry out orchestrated movement, what drives their assembly and their diverse functions, and how we can manipulate these machines into doing something new. I really like understanding the underlying mechanisms.


In the microbiology field, there is so much happening now with new technologies from imaging to sequencing. There seem to be endless new things to discover and understand. This might show new ways to treat bacterial infections or manipulate microbiomes to help people live better, which is a great long-term motivation.


Talking of goals, what motivates you to do your research?


It’s the problems and projects we work on in the lab. This can be discovering an unexpected phenotype or seeing something for the first time and thinking about what that could mean and how it can help us answer some long-term questions. I’m also excited when we see a certain structure for the first time. It’s a great source for new ideas and insights.


I get a lot of inspiration and joy from scientific meetings, collaborations and daily interactions with my colleagues and students. This makes my work exciting and fun.


What does receiving the EMBO Gold Medal mean to you?

It is an incredible honour to receive the EMBO Gold Medal. It is fantastic to know that there are people outside my research field who think that the work we do is exciting and important. I’m also happy about the recognition for the students and postdocs in my lab, without whom the work we do would not be possible.


This award is a great motivation for me to keep going with the work I do, to show people that microbiology is a fascinating research field and that one can uncover really interesting biology by studying bacteria.


You are an EMBO Young Investigator. How did this support your research?

I actually had an EMBO Long-Term Fellowship before I became a Young Investigator, so I have been part of the EMBO community for quite some time.


The Young Investigator Programme is great from a networking perspective: the diverse people from different research fields you get to meet and the chance to discuss the similar struggles you are experiencing. I also like the support you receive to go to meetings, for example. The more people you meet, the more you get invited and that helps to build your network. I’m very grateful for EMBO’s support.



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Tilmann KießlingTilmann Kießling
Head, Communications
T. + 49 160 9019 3839