“Decoding pathogen evolution”

Interview with new research group leader Felix M. Key

February 24, 2021

Felix M. Key joined the MPIIB in September 2020 to start his research group Evolutionary Pathogenomics. In his research projects, the computational biologist investigates the evolution of pathogens. He aims to answer questions about the adaptation and development of pathogens over vastly different time periods: What makes pathogens successful over centuries to millennia and how can they conquer new niches in patients within days? In this interview, Felix talks to us about his research projects, his move during the COVID-19 pandemic and the best place to find old bacterial DNA.

You moved to Berlin from the USA in July ‘20. How does a transatlantic move go in the middle of a pandemic?

My wife, our three children and I spent two years in Boston, where I worked as a postdoc at MIT. The pandemic hit Boston just as it hit Berlin. But unlike other states in the USA, Massachusetts is pursuing a strategy similar to Germany: Politicians are trying to protect the population and are relying on reason and science—accordingly, we had a “soft” lockdown. And just during this time we had to organize our long-planned move. The two months of July and August were probably the most exhausting of my life: We had hardly any childcare, two full-time jobs and on top of that we had to either liquidate or pack up our entire household and ship it from the USA to Germany. Fortunately, the dust is slowly settling. We are finally back to something that feels like everyday life.

Now you're here and you can start your research group in Berlin – what are your first steps?

For me, it's now all about establishing my group. I have to set up my laboratory and prepare my projects. At the same time, I have to finish my research project at MIT—dragging old projects to your new job is a classic—, but the end is in sight.

I'm also trying to build my team. Fortunately, I already hired a lab manager who has worked in the Molecular Biology department up to now. She is a huge help in getting the lab up and running. In addition, I made an offer to two very promising PhD students who will start their projects soon. We recently had our first virtual lab meeting and it was awesome. I am excited about what the future will bring.                                                                   

Your research group is called "Evolutionary Pathogenomics"what exactly are you working on?

I am interested in where pathogens come from and how they adapted to the human host. My research is focused on two completely different temporal dimensions: On the one hand, how pathogens evolved through thousands of years of human history and on the other hand, how bacteria of our own microbiome can evolve rapidly within days and make us sick.

So you are looking at very old pathogens?

The research field of "old pathogens" is very young. Only in recent years we have been able to follow the development of pathogens up to several millennia into the past by reconstructing their genomes. These molecular relics from prehistoric times allow us for example to uncover previously unknown epidemics. Nobody knew of their existence because there are no written records from that time.

I find it extremely exciting to look into the past and to investigate pathogens. Not only when they originated, but also where they came from. Many pathogens were first transmitted from animals to humans. I am particularly interested in the adaptive genetic changes that have contributed to the success of these pathogens. After all, some pathogens such as plague, tuberculosis and salmonella have been with us for thousands of years. They are extremely successful.

Our research is very interdisciplinary and we’re in contact with archaeologists and paleopathologists who examine archaeological material for diseases. We investigate our results also from a historical perspective: Are the pathogens we discovered in graves or settlements of a certain cultural period related to changes that were already described by archaeologists? Which new technologies emerged at that time, were there migratory movements, what kind of domesticated animals did they keep? This interdisciplinary view on biological data is a really exciting aspect of my work.

What is behind your research about rapid evolution?

For that area of research I am investigating how bacteria use their evolutionary potential to access new niches in the human microbiome. This potential is enormous! Trillions of bacteria are living in and on us, generating over one billion mutations. Every day!

We analyse samples from patients suffering from so-called hospital-associated infections. If a patient with a certain disease is admitted to hospital, he or she may also develop an infection. Up to now, it has been assumed that these patients are infected with bacteria that are found in large numbers at the hospital.

But there is a second way of infection: a patient may have brought the bacteria with him or her. When a patient’s immune system is weakened during his or her hospital stay, these bacteria take the opportunity to infect the patient. We want to take a closer look at exactly this process in our research.

How are these two fields related?

Both research fields are very similar in their fundamental questions: How do bacteria adapt to make us sick. We address this question by decoding DNA. In a nutshell, we generate large amounts of DNA sequencing data in high-throughput experiments, and perform extensive bioinformatic analyses to find patterns that teach us about the adaptation of bacteria. Ultimately, the biggest difference are the time periods, either we look at thousands of years or merely weeks.

Of course, data acquisition is very different. Either we cultivate bacteria from clinical samples or we drill into ancient archaeological specimen. Actually, teeth are the best choice for very old samples: Teeth are supplied with blood so they can contain pathogens that were present in the blood at the time of death. After the death of an individual, the teeth act as a safe and protect the pathogens from being washed out. With a bit of luck, we can find DNA snippets of the pathogen in the sample even after centuries and learn something about the disease.

Tell us a bit about your career so farhow did you end up in the field of evolutionary pathogenomics?

I actually thought that I would become an immunologist after my undergrad. But I was also interested in bioinformatics. Back then my girlfriend was pregnant and studied in Leipzig when I finished my undergrad in Greifswald—that's why I moved to Leipzig first. I was very open-minded about the topic at that time, but when I got to know Aida Andrés' research group at the Max Planck Institute for Evolutionary Anthropology, I was immediately hooked. It was a fantastic opportunity to learn about bioinformatics, population genetics and evolution. My PhD was about how humans have adapted to the different environmental conditions on our planet.

After my PhD, I was looking for new challenges. In 2015, researchers showed that bacteria can be reconstructed from millennia-old DNA. The scientists were able to prove that Yersinia pestis, the bacterium that caused the plague, is much older than expected. They extracted a plague species that no longer exists today out of 5000-year-old samples from the Bronze Age. The possibility to discover prehistoric epidemics from ancient DNA felt extremely captivating. Just in time, the Max Planck Institute for the Science of Human History opened in Jena. In the department of Johannes Krause, I got the chance to investigate old bacterial DNA methodically and analytically.

After two years as a postdoc, I wanted to extend my knowledge in clinical bacterial genetics. So I joined Tami Liebermann's group at MIT where we analysed bacteria of the skin flora of neurodermatitis patients. With my own group, I want to combine the acquired knowledge to better understand the origin and adaptation of pathogens.

You returned to a Max Planck Institute. Are you happy to be back?

The Max Planck universe is a fantastic environment to do research in Germany. I am very happy to be back and I am looking forward to getting to know my third Max Planck Institute. First as a PhD, then as a postdoc and now actually as a group leader. I would never have dreamed of this in the first place.

What fascinates you about research?

The unknown! As a computational biologist, I find nothing more exciting than searching through a data set and discovering something new. The data sets we work with are far too large to be analysed with the naked eye. My task is to skilfully extract, combine and visualize data from these sets: You see a certain aspect of your data in a graph and suddenly you understand the biology behind it!

A brief episode on that: In Jena we developed a method to search through thousands of different data sets simultaneously for all kinds of pathogens. After a lot of programming you hit “enter” and in the next moment you see disease patterns of the last 10,000 years in front of you—since the Stone Age. It was a moment of awe!

Interview conducted by Christian Denkhaus

 

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