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Immunopathology of Virus Infections

A systematic survey of P2Y receptors

Line’s PhD research is now published in EMBO! In this study, we systematically investigated the responses of human macrophages to extracellular nucleotides and revealed that adenine- and uridine-based nucleotides induce a specific and transient cytokine response through activating MAPK signaling pathway. We further categorized the nucleotide sensing P2Ys into two subgroups: P2Y1/2/6/11 that govern inflammatory responses via cytokine induction, and P2Y4/11/12/13/14 that directly induce antiviral responses.

Congratulations to Line, Yiqi, Chris, Lila, and all the collaborators involved in this study!

Read more in the EMBO paper:
Systematic P2Y receptor survey identifies P2Y11 as modulator of immune responses and virus replication in macrophages

Text by Yiqi, illustration by Line.

Goodbye Vince!

In early September, we waved goodbye to another dear member of the Innate Lab – Vince is moving back to Marseille for his new position at Beckman Coulter Diagnostics. We had another farewell party filled with lots of French wine and delicacies, lots of laughter and tears, plus one big French dance!

Dear Vince, thank you for being such an inspiration to the lab. You have been instrumental to our research in SARS-CoV-2 and beyond. Your energy and humour, and your extensive knowledge in virology, have a profound influence on all of us! We hope you’ll enjoy the sun and beach, as well as your new job in Marseille. Come back any time when you miss mountains and beer!

Here’s a selection of Vince’s work with us:

Text by Yiqi, photos by Anqi, Jyoti and Yiqi.

Identification of MDM2 as a regulator for SARS-CoV-2 uptake

We are excited to present our latest research publication! Building on our previous work (Stukalov et al., 2020, Nature), we investigated the impact of the genetic depletion of 21 host proteins on five different viruses. Our findings showed an increased SARS-CoV-2 replication in MDM2 knockout cells, which was virus-specific. This phenomenon can be attributed to the notable elevation of ACE2 levels in the absence of MDM2, thereby triggering an augmented SARS-CoV-2 uptake. Furthermore, our study highlights the crucial role of the MDM2 ubiquitination site Lysine 788 in stabilizing ACE2 and its significance in the context of SARS-CoV-2 particle uptake.

Congratulations to all the authors involved in this exciting research!

Read more here: MDM2 Influences ACE2 Stability and SARS-CoV-2 Uptake

Text and illustration by Quirin.

FOIL-VIII at Raitenhaslach

Amidst the heat of high summer, exactly a year after FOIL-VII, we went to Raitenhaslach again for the eighth FOIL- Future Of Innate Lab – retreat!

It is our great pleasure to have the 3-day retreat with the ArboSys lab, led by our dear alumnus Pietro. We learnt about each other’s projects during the flash talks and exchanged ideas in various aspects of our research. After mingling with the ArboSys colleagues, we all started to look at mosquitoes in amazement, just not the ones by Wöhrsee… As always, we made great plans for the future, some of which are already implemented since our return!  

We continued the fun tradition of Innate Olympics by Wöhrsee in the afternoon, where we performed our lab routines like cell transfer and sample labelling with some extra excitement. In the end, everyone won some prizes for the future, and we refreshed our group picture!

Three days passed swiftly, but the good memories will remain for a long time! We look forward to another exciting year of research at the Innate lab and are ready to combat virus infection together with the ArboSys lab!

Text by Yiqi, photos by Andreas, Anqi and Lila.

Congratulations and goodbye Dr Andersen!

On 24 July, Line successfully defended her thesis. Congratulations to Line – our Dr Andersen deserved her PhD not only in P2Y signalling but also in cake baking! It was a journey with lots of up and downs, but Line mastered the rollercoaster of P2Y with impressive diligence.

This Friday was Line’s last day in the lab. She organised a fantastic cocktail party for everyone and received a little surprise from us! Dear Line, we’re proud of your achievement and thankful for your contribution to the lab, especially in taming our qPCR Commander. You and your cakes will always occupy a sweet spot in our hearts (and adipose tissue). We wish you all the best in your new position in Copenhagen!

Text by Yiqi, photos by Melissa, cakes by Line.

TRR353: Death Decisions funded!

We are excited that our collaborative research center Transregio “Cell death decisions” (TRR353) has been approved for funding. TRR353 focuses on innovative and groundbreaking research related to the regulation of cell death decisions. Together with our colleagues at the University of Konstanz and the Albert Ludwig University of Freiburg, we will study how, why and when cells decide to die and how this can be exploited for therapeutic purposes. This funding will allow us to study the regulatory mechanisms of oxeiptosis, and the relationship of oxpeiptosis to other cell death pathways.

We are hiring PhD students for this project soon, so keep your eyes open!

Text by Lara.

Targeting host 2’O-methyltransferases to suppress Influenza virus

We are proud to be part of the massive effort, spearheaded by Hiroki Kato and his team from Bonn, that revealed the critical role of the host RNA 2’O-methyltransferase MTr1 in influenza A/B cap-snatching! The activity of MTr1 is pivotal for Influenza A and B but not for other cap-snatching viruses and can be inhibited by a host-directed small molecule to achieve an antiviral effect through a novel mechanism.

Congratulations to Hiroki Kato in Bonn and collaborators for the fabulous manuscript published in Science!

Read more here: Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication

Text by Valter and illustration by Andreas.

Bringing our research around the world!

As the world gradually recovers from the pandemic, we are also gradually resuming our physical conference attendance! Since the beginning of 2023, we have visited Ulm, Sitges (Spain), Paris (France), Snowbird (US), Gdansk (Poland), Crete (Greece), Würzburg, and certainly many more! Here’s what Innates have to tell about their experience:

Becoming a scientist involves learning to conduct science and socializing within the scientific community. Talking about current research and discussing future projects shaping the landscape of our research interests is vital for scientific progress. Therefore, I was thrilled to participate in the GfV, which allowed me to get to know top-notch virologists and comprehend Germany’s research interests. Although studies on SARS-CoV-2 were getting justified attention, I nevertheless felt that I was in good hands with my niche topic due to the size of the conference. For the first time, I had the opportunity to connect with scientists within my specialized field, enabling me to discuss this on a deeper level and understand how others are approaching similar goals.

On the other hand, broader and more international conferences, such as the 18th International Conference on Innate Immunity, gathered scientists from excellent research societies worldwide. It was a pleasure to be part of this gathering, hear talks about the discovery of novel signaling pathways, and meet the scientists behind it. All in all, attending conferences is just a win for you and your colleagues at home, who can profit from your reports and impressions.

I gave a talk about protein turnover in flu-infected cells at both conferences. GfV was my first-ever conference, and I fully enjoyed it! The atmosphere was really friendly, and I got to know many researchers with their interesting projects. A large number of students at the conference made it particularly easy to build connections. The conference had a lot of content, and I wish I had 10x the time to go through and absorb everything! Last but not least, it was great to meet our old colleagues Teresa and Pietro!

The 18th International Conference on Innate Immunity in Crete has a more relaxed and intimate setup with a more international group of scientists. It was an eye-opening conference and an excellent opportunity to hear about current trends in innate immunity! I learned a lot about different topics in innate immunity that we rarely touch in our lab and received many feedbacks and inspiration for my own projects. Besides, the food was amazing 😉

Cell Symposium: Viruses in health and disease (March 19–21, 2023, Sitges, Spain) was amazingly organized by Cell Press regarding novel insights on virus-microbiota interactions, SARS-CoV-2 structural biology and antiviral treatments, and emerging viruses. There, I presented our latest work focusing on the essential role of IKKα in the SARS-CoV-2 entry mechanism.

Additionally, I was selected to give a talk on this project at the French Days of the virology society (April 17-18, 2023, Paris, France). With the aim of developing Franco-German collaboration, our team joined great discussions at Pasteur Institute.

Thanks to Hao Wu, Russell E. Vance, and Andrea Ablasser for organizing the amazing Keystone conference “Innate Immunity: From Innate Sensing to Adaptive Responses” and giving us the opportunity to present our research. The time in Snowbird was an amazing opportunity to exchange with other researchers from all around the world.

It was a great pleasure to attend the 8th European Congress of Virology, taking place in Gdańsk, Poland, and organized by Prof. Thomas Mettenleiter from the Friedrich Loeffler Research Institute and Prof. Krystyna Bieńkowska-Szewczyk from the University of Gdańsk, where I did my studies. Returning to my hometown and reconnecting with the members of the lab that initially sparked my interest in virology, including my previous supervisor, Dr. Andrea Lipińska, alongside numerous current and former students, made the experience even more special. The conference brought together experts from a variety of subfields of virology and allowed me to appreciate unusual topics that I usually am not exposed to, such as the unusual split genomes strategy of multipartite plant viruses or the therapeutic potential of defective viral genomes of the flaviviruses.

I was selected to present my work at the 18th Innate Immunity Conference in Crete, Greece. This was a suitable theme for the future direction of my work, where I am focusing to explore the Innate specific proteins that are targeted by different variants of SARS-Cov-2. The major focus of this conference was inflammasomes and related pathways. I learned a lot about recent progress and directions in the cell death field and the NLRP protein family. Some topics were extremely interesting to me, like the “discovery of Panoptosis” and “Interferon exhaustion”. I received some valuable input from the researchers participating in this conference. There were good opportunities to connect with fellow researchers during coffee time, lunch, and dinner. The conference team also arranged a city tour, which was a fantastic experience. It was a great opportunity to connect with researchers gathering from different parts of the world and exchange ideas.

I had the opportunity to attend the Else-Kröner-Symposium in Würzburg. It was very interesting to see how results from basic immunology research were applied in clinical settings. To see the growing prevalence of translational approaches is promising and encouraging as it shows that our research has the potential to contribute to improving patients’ health in the future.

Where will we take our science next? Keep an eye on our homepage for future exciting updates!

Text and photos by the respective section authors.

Excellence initiative CiViA is funded!

Our colleagues from Aarhus University and us got funding for our joint excellence initiative Center for Immunology of Viral infections (CiViA). The Danish National Research Foundation will sponsor this initiative for up to 10 years!

In CiViA, we aim to discover novel antiviral mechanisms and unravel the decisive factors between protective and pathological immune responses. Moreover, besides providing spectacular infrastructure, we will team up with philosophers to prepare for the next paradigm shifts. We look forward to exciting times ahead!

Read more here: https://biomed.au.dk/civia

Text by Andreas.

Congratulations Dr Bergant!

At the end of May, another doctor graduated from our lab – congratulations to Valter (aka Dr Bergant)! Valter has conducted fantastic research during his PhD and wrote his thesis on “Data-driven host-directed antiviral drug repurposing against emerging pathogens”. He gave a great presentation at his defence that his committee would like to add infinite “summa” in front of “cum laude”. A huge well done from all of us! We are looking forward to your future contribution to the scientific community!

Read his first author papers here:

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

Attenuation of SARS-CoV-2 replication and associated inflammation by concomitant targeting of viral and host cap 2′-O-ribose methyltransferases

mRNA 3’UTR lengthening by alternative polyadenylation attenuates inflammatory responses and correlates with virulence of Influenza A virus

Text by Yiqi. Photos by Eva Lucija Kozak.