Single and double inhibition of complement and CD14 in opportunistic conditions

The group of professor Mollnes has worked with a combined inhibition of complement (at the level of C3 and C5), and the Toll like receptors (TLRs) targeting CD14, a key co-receptor for TLR4, TLR2 and others, based on an hypothesis to attenuating the upstream innate immune activation when it is over- or dys-activated. This occurs in conditions like sepsis, trauma and ischemia reperfusion injury. The effect of this combined inhibition has been shown both in vitro (human whole blood model) and in vivo (mice and pigs) with impressive effect on the detrimental inflammatory reaction, including activation of complement, cytokines, hemostasis and leukocytes induced by bacteria. Gram-negative E. coli and N. meningitides, as well as several Gram-positive Staphylococci species have been investigated with principally the same beneficial effects have been investigated. In this program we will investigate this therapeutic approach on opportunistic species including the fungi Candida and Aspergillus, which never has been studied in these models before. It will be a major scientific step forward to show whether fungi behave similar or different with respect to bacteria. Furthermore, inhibitors of the terminal pathway (C7) will be added in the program (produced by prof Würzner, Innsbruck).

The second part of this project will be to develop a commercial assay for detection of C3 activation. We have, for many years used an in-house assay based on the antibody bH6, characterized by professor Garred (Copenhagen). This antibody is unique in the sense that it detects a neoepitope which is exposed on the C3 molecule immediately after activation, but not on native C3. The epitope is exposed on C3b, iC3b and C3c, thus detection of the total amount of these fragments present in a sample. In collaboration with the company SVAR life science (Malmö, Sweden), this assay will be developed.

General description of your individual PhD-schedule:
• Your main university will be University of Oslo (Norway) with Prof. Mollnes as supervisor.
• You will have a 6-months research secondment at Medical University of Innsbruck (Austria) with Prof. Würzner as supervisor, where you continue to scientifically work on your thesis project.
• You will have a further 6-months research secondment at SVAR LifeSciences (Malmö, Sweden) where you will develop a new complement activation assay, based on the mab bH6, detecting a neoepitope exposed on C3 fragments.
• You will have a 1-month clinical training at Research Center Borstel Hospital (Borstel, Germany).
• You will have a 1-month entrepreneur training at SVAR LifeSciences.
• You will finally receive a PhD issued by University of Oslo and Medical University of Innsbruck if you fulfil the respective requirements.

Application
Please visit www.corvos.eu for application and more information on the PhD program. You have to submit: Application Form (see www.corvos.eu), CV, Master/MD/Diploma document, Abstract of Master/MD/Diploma thesis. Selected candidates will be invited for a personal interview to Innsbruck on 03rd/04thJan or 09thJan2020.

Requirements:
We are looking for highly qualified and motivated aspiring PhD students from any nationality with an open-minded and very enterprising personality, capable of working in collaborative and integrated research groups. Ideal candidates should possess a good scientific drive and a strong motivation to succeed.
•You have a full study completing degree (Master, Magister, Diploma, MD) in medicine, natural sciences or related disciplines until March 2020
•You are an Early Stage Researcher (ESR) – you either just finished your studies, or you have worked less than 4 years as an employee in the biomedical sector after obtaining your degree
•You have to show academic excellence, scientific potential, flexibility, motivation and suitability for the research project
•You have the willingness to stay abroad for 3 years from your current residence and willingness to travel through Europe
•You comply with the mobility rule for Marie Sklodowska Curie ITN fellows – Researchers must not have resided or carried out their main activity (work, studies, etc.) in the country of the recruiting university for more than 12 months in the 3 years immediately before the recruitment date. This will be thouroughly checked.