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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.
The European Meeting on Complement in Human Disease, Bern, 2022, organized by Robert Rieben and his team was the first complement meeting in person after the Corona crisis and a lot of CORVOS housekeeping issues were discussed in person, including an official CORVOS Supervisory Board Meeting, organised by the CORVOS & HOROS administrator Silke Huber. A new CORVOS flyer was presented.
In addition, another teaching lecture was held on how to create a good poster and a CORVOS group photo was shot afterwards.
Virtually all CORVOS students were present as well as their supervisors. Excellent presentations were given at the conference, namely two oral presentations and 14 talks (see list). The networking highlight was the boat trip on Lake Lugano.
HOROS students working on complement (Verena Harpf und Sara Kellnerova) discussed future collaborations with their CORVOS peers.
CORVOS & HOROS speaker finds „his“ shop“
CORVOS flyer
CORVOS teaching lecture on how to create a good poster
CORVOS group picture
List of CORVOS contributions
Conference Dinner 1
Conference Dinner 2
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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.
We are delighted to congratulate Max on successfully completing his PhD! His thesis provided valuable insights into the role of the complement system in the innate immune response, focusing on the pathogens SARS-CoV-2 and Aspergillus fumigatus.
Max's research comprised three significant studies:
(1) Max developed a sensitive MASP-2 ELISA to investigate its association with COVID-19. He found that MASP-2 concentrations were significantly increased in COVID-19 patients compared to healthy controls and correlated with age, female sex, and higher mortality. Additionally, MASP-2 levels were linked with terminal complement complex (TCC), ficolin-2, ficolin-3, and C-reactive protein (CRP), suggesting MASP-2 as a potential biomarker for COVID-19.
(2) By exploring the binding kinetics of pattern recognition molecules (PRMs) of the complement system on pathogen surfaces, Max discovered that C1q and MBL rapidly bound and then detached from pathogen surfaces within minutes in plasma, a process associated with complement cascade activation. C1q detachment was linked to the activation of the C1 complex, while MBL dissociation relied on overall complement activation and solubilization via C3b.
(3) Max investigated the innate immune responses to A. fumigatus in whole blood, finding that it triggered complement and leukocyte activation, similar to E. coli. Although A. fumigatus induced a less extensive cytokine response compared to E. coli, complement inhibition significantly altered the release of six key cytokines, indicating the complement system's role in cytokine release. The expression of most cytokines depended on the monocyte fraction in whole blood.
Collectively, these studies demonstrate the significant role of the complement system in infections with SARS-CoV-2 and A. fumigatus. Max's work highlights the potential connections between cytokine release, pathogen opsonization, and the detachment of C1q and MBL from microorganisms, though further research is needed to fully understand these mechanisms.
We wish Max the best of luck for his future academic career.
We are thrilled to announce that Beatrice has successfully graduated with her PhD! Her thesis explored the human innate immune system using the lepirudin whole blood model. This model, introduced in 2002, uses the anticoagulant lepirudin to maintain complement system function while preventing blood coagulation. Beatrice's work involved collecting blood in lepirudin-treated tubes, exposing it to various activators, and analyzing cell activation markers, complement activation, and inflammatory mediators.
Beatrice's thesis consisted of three significant papers:
Paper I: Beatrice developed a novel model by selectively removing individual cell populations, revealing the specific roles of monocytes and granulocytes in cytokine release. This study was published in the Journal of Leukocyte Biology.
Paper II: She investigated the inflammatory response to Aspergillus fumigatus conidia compared to Escherichia coli, identifying CD14+ monocytes as key contributors to cytokine release. This paper was published in the Journal of Innate Immunity.
Paper III: Beatrice adapted the model to study patients with acute myelogenic leukemia (AML) undergoing hematopoietic stem cell transplant (HSCT). The study showed that AML patients maintain a functional complement system throughout the transplantation period. This paper is under revision for publication in Frontiers in Immunology.
Collectively, these papers enhance our understanding of innate immune responses and pave the way for new targeted therapeutic strategies.
We are incredibly proud of Beatrice's achievements and wish her all the best in her scientific career.
On the 11th June 2024 two CORVOS ESRs Hang Zhong (IT-1) and Mikel Rezola Artero (FI-2) participated in the 16th International Conference on Complement Therapeutics. They showcased their research through oral presentations and flash poster talk sessions which stimulated scientific discussion and provided invaluable feedback on both projects.
This meeting in Loutraki, Greece, provided an opportunity to bring together complement experts from both academia and industry. Participants shared new data and discussed the latest developments in therapeutic design, clinical trials, and new aspects of complement-driven pathophysiology.
Following an intense, one week program on a wide variety of topics ranging from complement-driven haematological/ocular/kidney/neurological disorders to complement in infectious diseases, the conference finished with a farewell dinner where all the participants enjoyed live music and had the opportunity to learn some local dances. Finally, the evening culminated in the announcement of the awards, where both of the ESRs received trainee awards due to their commendable contributions to the conference.
We are delighted to announce that Mariam has successfully completed her PhD! Her research focused on the complement system, specifically the component C7, which is crucial for the assembly of the membrane attack complex (MAC). While the structure and function of C7 in MAC assembly are well documented, Mariam's work aimed to uncover the non-canonical roles of C7, which are less understood. Mariam's thesis explored several key areas: (1) Extrahepatic Synthesis of C7: Unlike most complement proteins, C7 is primarily synthesized outside the liver, allowing it to regulate local MAC assembly. This unique synthesis pathway suggests that C7 could play distinct roles in different tissues. (2) Association with Disease Pathogenesis: Emerging studies have linked C7 with various diseases, highlighting the need for further investigation into its non-canonical functions. (3) Development of Monoclonal Antibodies (mAbs) and Immunoassays: A major aim of Mariam's research was to create reliable tools for characterizing C7. She developed monoclonal antibodies that specifically bind to native C7, which were then used to establish an enzyme-linked immunosorbent assay (ELISA) for measuring C7 in different matrices. This novel ELISA demonstrated high specificity and no cross-reactivity with similar proteins. (4) Interaction with Clusterin (CLU): Mariam's investigation into the regulatory role of C7 revealed a significant association with the complement inhibitor clusterin (CLU). Her work indicated the presence of a C7-CLU complex in circulation, suggesting that C7 has multifunctional roles beyond its traditional functions in MAC assembly.
Mariam's innovative research has provided new insights into the complex roles of C7 and developed valuable tools for future studies. We are incredibly proud of her accomplishments and wish her all the best in her scientific career.
