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Generation, characterisation and commercialisation of native-restricted and neoepitope-specific monoclonal antibodies directed against the terminal complement protein C7

  • Full or part time
    Prof R Würzner
    Prof Z Prohaszka
  • Application Deadline
    Sunday, November 10, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

Complement is one of the most important players in innate immune defense. Three activation pathways are triggered by multiple interactions and are amplified in cascades, leading to the activation of the terminal complement (TC) pathway. This pathway is especially important in Neisserial infections, and thus subjects deficient in these TC components are particularly affected by these gram-negative bacteria. Furthermore, insufficiently protected human cells (for various reasons) are also attacked. Of the several TC proteins C7 plays a particular role, as it is the only component predominantly synthesized extrahepatically. Thus, locally produced C7 will enhance complement attack at the site of inflammation.
Monoclonal antibodies (mabs) against C7 are already available, but those which are clearly native-restricted or neoepitope-specific are lacking. The former will detect only native C7 and may even block TC complex assembly, whereas the latter may be useful for the quantitation of this complex. The aim of this PhD thesis project is the generation and commercial production of anti-C7 mabs.
To achieve the goals, first, short amino acid regions of C7 will have to be identified, especially those which are likely accessible in either the native or the incorporated C7 protein, of which the former may be likely involved in TC pathway interactions. Peptides, representing these sequences will be used for immunization of mice to generate specific mabs, very likely with a partner in Copenhagen (DK). The first intensive tests, however, will be performed in Innsbruck. A thorough control evaluation using an array of different kits will follow at the Semmelweis University in Budapest (HU) for 6 months, where the inhibitory and potentially connected therapeutic functions of these mabs will be assessed. During another 6-months stay at the biochemical company Hycult (NL), all suitable mabs will be conditioned for good manufacturing practice and mass production to coin commercial products, when all IPR issues have been accomplished.

General description of your individual PhD-schedule:
•Your main university will be Medical University of Innsbruck (Austria) with Prof. Würzner as supervisor.
•You will have a 6-months research secondment at Semmelweis University (Budapest, Hungary) with Prof. Prohaszka as supervisor, where you continue to scientifically work on your thesis project.
•You will have a further 6-months research secondment at Hycult Biotech (Uden, Netherlands) where you will use your mAbs for development of commercial assays.
•You will have a 1-month clinical training at University Hospital Helsinki (Finland).
•You will have a 1-month entrepreneur training at Hycult Biotech.
•You will finally receive a PhD issued by Medical University of Innsbruck and Semmelweis University if you fulfil the respective requirements.

Application
Please visit http://www.corvos.eu for application and more information on the PhD program. You have to submit: Application Form (see http://www.corvos.eu), CV, Master/MD/Diploma document, Abstract of Master/MD/Diploma thesis.

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.

Funding Notes

The Marie Sklodowska-Curie project CORVOS, for COmplement Regulation and Variations in Opportunistic infectionS, is funded as an Innovative Training Network (ITN) – European Joint Doctorate (EJD). Its focus lies on education of young scientists in the field of complement in opportunistic infections. This interdisciplinary doctoral program is supported by 10 European universities, 2 research institutes, 3 biomedical companies and 3 hospitals. The PhD students will have enhanced career perspectives in the academic and non-academic sectors through international, interdisciplinary and inter-sectoral mobility combined with an innovation-oriented mind-set. Visit View Website to see all the benefits that you will have as CORVOS PhDstudent.

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