Ralf Grutza
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Final year Ph.D. student Ralf Grutza on CMV and the immune system

Ralf Grutza sheds some light on what it’s like to be a final year Ph.D. student in the Institute of Virology at the University Hospital in Dusseldorf. Since October 2018, Ralf has been studying cytomegalovirus (CMV) seropositive individuals to figure out how the virus evades the immune system and changes the immune response to other viral infections.

What got you interested in science, and when did you decide you wanted to do a Ph.D.?

I’ve always been a curious person. I like planning experiments and discovering new things – it’s a lot of fun.

During my degree, I was lucky enough to work in a virology lab at the same university where I’m doing my Ph.D. As a result, I learned many different molecular biology techniques and had the chance to speak to other students, which helped me realize that I wanted to come back to do my own research.

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I’ve always been a curious person. I like planning experiments and discovering new things – it’s a lot of fun.

What do you find most interesting about your research?

CMV itself. We’ve known about the virus for a long time, but there are always new things to discover. It’s an expert at evading the immune system, so once you’re infected, you’re CMV positive for the rest of your life. It’s interesting to study the evolutionary race – the immune system reacts, the virus responds. It’s so impressive that something so tiny can continue to outsmart our complex immune system.

The clinical aspect is also fascinating. If you look globally, prevalence can reach up to >90% in some populations, depending on socioeconomic factors and age. Most people can live with CMV without any complications, but it can be life-threatening for immunocompromised patients, and there’s currently no cure. I hope that by studying the basic biology of CMV, we might be able to change that.

You’re also studying how CMV affects the immune response to other viruses; what have you learned so far?

Well, that’s really interesting. CMV has so many immune evasion mechanisms and can change the phenotype of our immune system over time. In my first publication, I could already show that CMV-associated NKG2C+ NK cells can kill HLA-E high expressing targets, which can lead to an inhibition of the CMV-specific CD8 T cell expansion.

I’ve also been comparing CMV positive and negative patients and seeing how they respond to other viral infections or vaccinations. One study I’m working on at the moment is looking at how CMV-positive patients respond to the influenza vaccine. In a second study, I´ll be comparing the immune response after a SARS-CoV-2 vaccination. The collection of samples from this cohort was initiated by Lisa Müller, Dr. Marcel Andrée, Professor Heiner Schaal and Professor Ortwin Adams. I will do a retrospective analysis of it.

That’s fascinating and very topical; what are the results of the vaccination studies so far?

We’ve already started collecting blood samples from SARS-CoV-2 and influenza vaccinated patients and measuring their humoral response and CMV status. There’s a lot of discussion in the literature about the impact of CMV serostatus on the humoral response to vaccination, so I hope we can contribute to that with our two cohorts.

The advantage of our study is that we’re comparing two cohorts with different vaccines, and there’s a high number of elderly people enrolled in Müller and Dr. Andrée’s cohort. Some publications have shown that CMV is connected with accelerated immune aging, and age is already connected with a weaker immune response after SARS-CoV-2 vaccination1. We are now summarizing the data and hope to publish it soon.

What was it like working during the pandemic?

It was an interesting and sometimes frustrating time to be working in research. I couldn’t collect all the samples I need for my influenza study, and we had to plan differently as a group. Like many other research labs, we couldn’t be in the lab at the same time, we had a lot of delivery problems, and we ran out of pipette tips. Some colleagues also switched completely to coronavirus research, so it was fascinating to discuss and see firsthand how this new, important research was progressing.

Have you published your work, and how was that?

Yes, in April 2020, I published my first first-author paper in the Journal of Immunology2. I was really proud of that. It was a new process for me, so I was grateful to have the support of my colleagues. Without them, it would have been much harder. It was a relief to publish in the first few years of my Ph.D. as it means less pressure in my final year. It’s also really cool to be able to search your name on the internet and see your research pop up.

We’d like to follow up with you in the next few months; what do you have planned?

The next few months will be interesting for me as my contract ends soon. I’ll be primarily focusing on getting my data together and writing it up. It’s been a big hurdle for me to accept when to stop doing experiments. If something isn’t perfect, you want to go back and do it again, but at some point, you have to draw the line. I have a few more experiments to do with the samples we collected from the influenza vaccine cohort, and I have to make some plans with the MSc student I’m mentoring.

How has writing up your thesis been so far?

I knew from the start that my thesis would be on CMV, so I started writing some of the introduction quite early on. At the moment, I’m putting all my data together, and I recently had a meeting with my supervisor to discuss how we could tell the best story. At first, I didn’t think I had that much data, but now I’m putting it all together, I’m thinking, “wow, ok, which data do I choose? What fits the story?”

Do you know what you’d like to do after your Ph.D. ?

I really want to stay in the field of research and development. I now have experience in academia and industry, and both have their pros and cons. Continuing to work on my own research in academia would be interesting, but it’s challenging to get a “safe” job. Industry is more secure, and I would still be doing research, but there’s no guarantee that I’d always be working on projects that fit my interests. It’s hard to decide, but I would be open to both options if the project interests me.

How was your experience in industry, and how does it compare to academia?

Industry was fun and cool. I got to work in the Instrument and Detection Group at QIAGEN. I initially planned to do a six-month project as part of my MSc, but I felt that I needed more experience, so I ended up staying for 11 months.

The main difference between academia and industry is that the goal is different. In academia, it’s publishing papers, and in industry, it’s making a commercial product, but both come with their own challenges and pressures.

What advice would you give someone at the start of their Ph.D. ?

I would say do a lot of literature research. Take your time to understand the topic before planning experiments. Also, speak with other people in your group. Over time, they will help you and you will help them. Of course, experiments will fail, and you will have to keep trying, but there’s always someone else in the lab having a similar experience - drink a beer together and talk about it.

What advice would you give someone who’s thinking of doing a Ph.D. ?

You should know what frustration is. You need to be on fire for the topic. Don’t do it just to get letters in front of your name.

It’s also good to get experience; even a short internship is helpful. I wanted to see what industry research would be like, so the internship at QIAGEN really helped with that. The interview was hard, but it was worth it. It’s not very common for MSc students to do their research project in industry, but I would highly recommend it, especially if you’re considering working in industry in the future - experience is essential.

When you’re not busy in the lab or writing up your thesis, what do you enjoy doing?

I love music, and I’ve been playing guitar since I was 5 years old. When I was 17, I had to decide between a career in music or science. I chose science as it’s very diverse and there are more job opportunities.

I also cannot be without soccer. I started playing from an early age, and I would often go to the stadium with my friends and family to watch Bayer Leverkusen play.

In the first year of my Ph.D. I had more time for hobbies, but now I’m in my final year and writing up; that’s where I focus most of my time.

Selected Papers
  1. Lisa Müller, Marcel Andrée, Wiebke Moskorz, Ingo Drexler, Lara Walotka, Ramona Grothmann, Johannes Ptok, Jonas Hillebrandt, Anastasia Ritchie, Denise Rabl, Philipp Niklas Ostermann, Rebekka Robitzsch, Sandra Hauka, Andreas Walker, Christopher Menne, Ralf Grutza, Jörg Timm, Ortwin Adams and Heiner Schaal. Age-dependent immune response to the Biontech/Pfizer BNT162b2 COVID-19 vaccination. Clin Infect Dis. 2021. https://doi: 10.1093/cid/ciab381
  2. Ralf Grutza, Wiebke Moskorz, Tina Senff, Eugen Bäcker, Monika Lindemann, Albert Zimmermann, Markus Uhrberg, Philipp A. Lang, Jörg Timm and Christine Cosmovici. NKG2Cpos NK Cells Regulate the Expansion of Cytomegalovirus-Specific CD8 T Cells. J Immunol, 2020 DOI: https://doi.org/10.4049/jimmunol.1901281
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