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On the 16th of September 2022 researchers from the Medical University of Innsbruck met at the 8th CIIT Science Day with CORVOS & HOROS, which had been organized with great commitment by Thomas Sonnweber, Doris Wilfingseder and Wilfried Posch. In the seminar rooms of the MZA, allocated researchers and PhD students presented almost 50 current research projects in demanding poster sessions. Additionally, Univ.-Prof. Dr. Andreas Bergthaler from the Institute of Hygiene and Applied Immunology (Medical University of Vienna) was invited to the event and delivered an exceptional keynote lecture. The lively scientific exchange followed by a light buffet with drinks made this year’s Science Day a resounding success. We want to thank all people involved in the organization and the participants for this interesting and stimulating meeting.
On September 19th, 2022, members of the CORVOS and HOROS programmes visited the Meinhardinum in Stams, a high school located in the heart of Tyrol, Austria, to bring pupils closer to research and scientific work. After an introduction about the CORVOS and HOROS programmes by Prof. Würzner, the speaker of CORVOS and HOROS, in front of three final-year classes, PhD students individually presented their cultural background and their motivation to achieve a PhD. This was done in smaller groups, i.e. in three class rooms. Since all PhD students were female, pupils got the view that everybody, independent of gender, can find a place in science. In addition, the role of females in science was particularly discussed. Furthermore, students talked about their experiences and acquisition of subject-specific and soft skills during their studies. Finally, pupils had the chance to ask any questions regarding their potential scientific future. We hope that our enthusiasm for research inspired some of the pupils to strive for a career in science and to aim for a doctoral degree. Overall, it was a very nice experience for both sides, pupils and PhD students.
In the beginning of January, three ESR students, Julia, Hang, and Carmen participated in our industrial secondment at MSD Finland. Due to the corona restrictions, the programme was mainly held remotely. During the secondment month, we got the opportunity to meet the MSD team based in Helsinki and obtained an overview of how the global pharma business operates, communicates with the clients and the public, and develops client relationships, through meetings with the Managing Director of Finland, Quality Assurance specialists, Therapy Area Manager, communication specialists, marketing, strategic account, and territory area leads and so on. Furthermore, we learned the important role of the policy lead for reviewing and drafting policy instruments. We were also introduced to pharmacovigilance and medical director who are responsible for the assessment of product safety, prevention of adverse effects of medical products, and communication with doctors and experts.
Moreover, we were invited to a guided tour in MSD Finland with Michael Pasternack, where we were interviewed about our experience of the industrial secondment with MSD under CORVOS. Since the beginning of the industrial secondment, one buddy had been assigned to each of us for preparing their talk for the collaborative webinar ABC of infections and immunity, to be held towards the end of the industrial secondment. We three ESRs chaired, and organized the webinar: ABC of infections and immunity. Together with the invited speakers, who are scientists from the University of Helsinki - Prof. Seppo Meri, Prof. Mikael Skurnik, and Dr. Karita Haapasalo they presented their research field followed by discussion sections with the audience.
A big thanks to Dr. Marjut Puputti-Laurila, Dr. Annette Gylling, and Dr. Riku Korhonen for accompanying and helping us ESRs students to prepare our presentation for the webinar. Finally, we would like to show our deepest gratitude to Michael Pasternack and Tuomas Peltonen from MSD, and Prof. Seppo Meri and Liisa Penttila, for organizing our secondment, which has given us an insightful experience.
In the early months of 2022, CORVOS ESRs Beatrice Fageräng, Leon Cyranka and Pedro Medeiros had their entrepreneurship training at SVAR, a Swedish company focused on inventing, developing, and applying assay technology for drug development and clinical diagnostics.
During this period, the organization and facilities of the company were shown, as well as new ideas of synergies for the CORVOS' projects together with SVAR's complement portfolio were discussed.
While Beatrice and Pedro had their time dedicated to the development of a commercial C3bc ELISA based on mAb bH6, Leon tested C5aR1 antibodies via the iLite® system.
Special thanks to Anna Prahmed and Katarina Håkansson Frendéus for welcoming our entrepreneurship training and the whole team of SVAR Life Sciences.
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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.
