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On June 19th, 2023 Lisa was the first of our excellent CORVOS students to defend her thesis. In the past three years, she developed immunoassays for the measurement of C1s/C1-INH complex and MASP-1/C1-INH complex in human serum and plasma. Finally, these assays were characterized and validated in cohorts of COVID-19 and sepsis patients. Both complexes were proven to be specific biomarkers for early classical and early lectin pathway activation. Lisa was supervised by Prof. Zoltán Prohászka, MD, PhD from the Doctoral School of Theoretical and Translational Medicine Semmelweis University, Budapest, Hungary and Prof. Reinhard Würzner, MD, PhD from the Institute of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria. In addition to her main studies in Budapest, Lisa spend 6 months at the Medical University of Innsbruck (Austria), did 1 month clinical training at the University Hospital in Helsinki (Finland), did 1 month of industrial entrepreneurship and 6 months industrial secondment at Hycult Biotech (The Netherlands). Congratulations, welcome to the Alumni club and all the best for your future.
Doctoral training prepares doctoral candidates for their future careers in a constantly changing society. In this context, MUI is a member of the Organisation for PhD Education in Biomedicine and Health Sciences in the European System, or ORPHEUS, which aims to safeguard the PhD as a research degree by supporting graduate schools, faculties and departments, research students and their supervisors, through quality assurance mechanisms, advocation of best practices, professional development and training.
At this year’s ORPHEUS conference, which took place from the 13th to the 15th of April in Leuven (Belgium), alongside international keynote speakers and presenters selected from submitted abstracts, CORVOS Speaker Prof. Dr. Reinhard Würzner and CORVOS ESR Dr. Pedro Medeiros showcased how CORVOS has been successfully implemented in several European countries. At the annual meeting, opportunities and challenges associated with these contemporary elements of doctoral training and research activities were also discussed. There were namely workshops, panel discussions, presentations and poster sessions, meeting new colleagues and several networking possibilities.
On February the 27th 2023, four CORVOS ESRs began their industrial entrepreneurship secondment at SSI DIAGNOSTICA and AJvaccines. The ESRs (Alejandro, Frerich, Maximilian, and Michal), started at SSI Diagnostica in companionship with Professor Karen Angeliki Krogfelt. On the first day, they were introduced to a wide variety of basic knowledge of Legionella & Pneumococcus bacteria, their epidemiology and serotyping, associated diseases, and diagnostics led by Pernille L. Elverdal. Later that day, the Ph.D. candidates were introduced to the development of lateral flow tests by Ian C. Skovsted, one of the main business branches of SSI Diagnostica.
The next day, the ESRs applied the theory and developed and assembled their very own lateral flow assays. In the afternoon, they learned about Pneumococcal antigens and how SSI Diagnostica conducts research and diagnostics on Pneumococcus. Later that day, the students were introduced to the different bacterial identification methods and the new products that the company is developing for testing resistant bacteria, phenotyping, and serotyping them.
After an exciting day producing a range of their new products and learning about some specific pathogenic bacteria, the ESRs went to dinner with many of the SSI DIAGNOSTICA employees as well as the host, Professor Krogfelt. The students shared some common outlooks and perspectives regarding what to do after obtaining the Ph.D., and they got a lot of helpful feedback, as well as some input from people that have been in the industry for a long time. Another successful network opportunity within the scope of CORVOS.
On the last day at the company, the Ph.D. students visited the laboratories again and were introduced to the different working areas regarding Salmonella and E. coli, their epidemiology and serotyping, as well as the production line for some specific products for diagnosis of bacterial identification. Later that day, the students met the head of R&D, Karen Korsholm, to talk about new developments on their Luminex. Finally, the ESRs were introduced to the new legislation regarding IVDR, how much this impacts the product pipelines and what is needed to make a CE-certified kit. After those information-packed and engaging days at the company, the students decided to join Prof. Krogfelt at the Louisiana museum of modern arts for a get-together and some informal conversation about future perspectives in industry or academia.
The next day, the students visited another company, AJvaccines, where they met Sylvester Larsen and received an introduction to the production of the polio vaccine. AJvaccines being one of the last manufacturers of this crucial vaccine. They also got to know about the production of the BCG vaccine, the BCG culture for cancer treatment and the production of their tetanus vaccine. After this session, the students took a guided tour of the polio vaccine production facility. With this, the students said their goodbyes to the fantastic host Professor Krogfelt who made it possible to experience this opportunity and gain all of these new insights into the industrial processes.
As last year, our retreat to the beautiful Obergurgl could be held from 07th to 9th of January 2023 - this time without restrictions. Once again members of two PhD programmes of excellence, HOROS (Host response in opportunistic infections) and CORVOS (Complement regulation and variations in opportunistic infections) as well as local PhD candidates from the IIT (Infection, Immunology, and Transplantation, Innsbruck, Austria) program came together to enjoy scientific discussions and do networking to push their research projects forward. Renowned scientists from across Europe, including Jörg Köhl (Lübeck, Germany), Seppo Meri (Helsinki, Finland), Tom Eirik Mollnes (Oslo, Norway), Peter Garred (Copenhagen, Denmark), Zoltán Prohászka (Budapest, Hungary) Mohamend R. Daha (Leiden, Netherlands) representing CORVOS as well as Christian Karsten (Lübeck, Germany) and Mikkel-Ole Skjødt, both member of the HOROS advisory board, participated and inspired with their talks. Especially for our PhD candidates it was a perfect environment to prove their scientific and presentational skills in front of experts in the field of opportunistic infections and immunology in a relaxed and private atmosphere. Additionally, representatives of the CORVOS industrial partner Hycult Biotechnology (Uden, Netherlands), namely Loek Willems, Eirik Toonen, and the CEO & Owner Ronald de Niet as well as of the company Novartis (Schaftenau, Austria), Marco Grasse (former CORVOS Administrator) were present.
Besides a tight schedule, there was still time for networking and team building with PhD students and principal investigators. The majority of participants enjoyed skiing at the lovely nearby slopes or assisted one another in learning how to ski while some went hiking or sledding. Another highlight was ice-skating were we played the popular Hungarian “catch on ice” game. No matter the favorite sport, they were all ideal for interacting with other scientists.
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The European Meeting on Complement in Human Disease, Lübeck, 2024, organized by Jörg Köhl and his team was the official international farewell event for CORVOS with a concluding meeting meeting.
The final report had been accepted well before and the speaker, Reinhard Würzner, was proud to announce that all projects were successfully accomplished (due to the Corona crisis some had to be changed, though, but most actually to the better and a lot of CoCo papers (for Complement & Corona) were published by the CORVOS consortium). After the meeting the consortium met at the Schiffergesellschaft where the Speaker delivered some final words and the CORVOS aprons in the courtyard. The dinner was afterwards in the very picturesque halls.
Time to say goodbye to some members of the consortium, but others were looking forward to another Obergurgl retreat in early January 2025. Thus, CORVOS is still flying....
Together, these three studies form a cohesive body of work that significantly advances our understanding of the complement system in various clinical contexts. The novel antibody targeting C5aR1 offers a promising therapeutic tool, while the stem cell transplantation study challenges our understanding of immune dynamics during transplantation. Finally, the exploration of complement modulation in whole blood emphasizes the potential of complement-targeted therapies in infectious diseases.
The successful defense marks the culmination of years of rigorous research and sets the stage for further advancements in the field. As the research moves forward, it holds promise for better therapeutic strategies for autoimmune diseases, transplantation, and infectious diseases.
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We are happy to share that Julia successfully defended her PhD in Paris on December 18th, 2024. Her doctoral dissertation focussed on acquired abnormalities in complement-mediated glomerulonephritis, and highlighted three studies :
Study I: Functional characterization of anti-C3bBb autoantibodies and C3 Glomerulopathy phenotype. Julia has developed new biochemical assays to identify IgG autoantibodies targeting the C3BbB convertase, and found association of autoantibodies function with the complement alternative pathway overactivation and the disease severity of C3 Glomerulopathy.
Study 2: Spectrum of anti-factor B associated glomerular diseases in adults. Julia highlighted that anti-Factor B was strongly associated with infection-associated glomerulonephritis. The functional characterization of these autoantibodies highlighted the proconvertase C3bB formation and the C3bBb stabilization as two important mechanisms of alternative pathway dysregulation.
Overall this work provides new pieces in our understanding of the pathophysiology of complement-mediated glomerulopathies but also paves the way for the use of new diagnostic assays for C3bBb convertase targeting autoantibodies and complement-targeted therapies to improve patient outcomes.
On a cold December day in Helsinki, the 13th December 2024, Mikel Rezola Artero defended his PhD successfully to gain a PhD from University of Helsinki and University Sorbonne in Paris. In his thesis, entitled “Mechanisms of complement subversion in Infection and cancer” he compared the evasion strategies pathogens and tumour cells employ to evade the complement system.
On the pathogen side, he explored how P. falciparum sporozoites resist complement attack through hijacking of the complement regulator C4b binding protein (C4bp).
On the tumour side, he investigated the mechanism behind the pro-tumoural role of intracellular factor H (FH) by a combination of transcriptomics in patient tumours, cellular and biochemical assays that demonstrated that intracellular FH acts as a multitasking tumour-promoting effector by regulating cell cycle progression and by maintaining cytoskeleton organization.
Thus both pathogens and tumour cells employ different, but on the other hand, similar mechanisms.
Ruben Pio Oses, Navarra, Spain, who was also a referee of the thesis earlier, acted as opponent. The other referee, and speaker of CORVOS, Reinhard Würzner, Innsbruck, Austria, was also in the evaluation committee on site. The two supervisors, Seppo Meri, Helsinki, Finland and Loubka Roumenina, Sorbonne, Paris, France were also present. The evening before, the candidate and the invited guests met at a typical Karelian restaurant and after the defence in the prestigious and picturesque Villa Aikala with a Lebanese buffet.
Congratulations to Mikel for his remarkable accomplishment!
We are pleased to announce that Michal successfully defended his PhD thesis on October 25, 2024. His work focused on the complement evasion mechanisms developed by human pathogens, mainly Acinetobacter baumannii, Klebsiella pneumoniae, and Streptococcus pyogenes.
Papers I and II were dedicated to A. baumannii, a worrisome complement and antibiotic-resistant pathogen. In these papers, Michal screened many isolates from the genus Acinetobacter and aimed to characterize their MAC evasion strategy. He found two potential mechanisms worthy of further investigation.
In paper III, the focus switched to K. pneumoniae, another serious human pathogen. This study highlighted a surprising connection between complement and colistin resistance in isolates obtained from patients. This study delivered results worth considering in the epidemiology of Klebsiella infections.
Paper IV aimed to provide a treatment option that counteracts the complement evasion mechanism in S. pyogenes. This bacterium acquires the complement inhibitor factor H from serum to evade opsonization. Replacing the serum-bound inhibitor with the FH6-7/hFc fusion protein increased complement activation and resulted in better animal survival in the mouse model. This protein highlighted the possibility of using bacterial evasion mechanisms against the bacteria themselves.
Taken together, Michal's findings gave us a better overview of bacterial infections and their complement evasion mechanisms. As antibiotic resistance among human pathogens becomes more serious, novel treatment options are needed.
We wish Michal all the best for his future career and research projects.
