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Identification of novel complement evasion mechanisms developed by bacterial pathogens

  • Full or part time
    Prof A Blom
    Prof S Rooijakkers
  • Application Deadline
    Sunday, November 10, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The project is focused on discovery of new complement evasion mechanisms developed by bacterial pathogens. One of the studied bacteria will be opportunistic Filifactor alocis, a recently identified periodontal pathogen of major importance but still poorly studied. Filifactor is exceptionally resistant to complement-mediated killing (i.e. serum resistant) and likely several evasion molecules/mechanisms will be identified. This will be achieved using advanced methods such as phage display of secreted proteins and transposone mutagenesis of all genes. Once established, both methods will be also applied to other clinically relevant bacterial pathogens, Porhyromonas gingivalis (transposone) and Neisseria (phage display). In the next step, the identified proteins will be recombinantly expressed, purified and studied in detail for their effect on all steps of the complement cascade using methods already well established in the group. Further, deletion mutants or knock-ins of the relevant genes will be created in bacterial strains to assess their relevance in context of the whole organism. The prevalence of expression of the identified virulence factors will be assessed in collections of clinical bacterial strains available in the group in order to assess if they are broadly expressed and thus could be targeted for therapy. Further, we will test new therapeutic approaches based on identified virulence mechanisms, including testing fusion proteins, which utilize the fact that many bacterial pathogens capture human complement inhibitors such as C4BP or factor H.
The student will have opportunity to learn many microbiological methods, protein expression, purification and analyses, protein interactions (Biacore), flow cytometry, complement-specific assays, confocal and STORM superresolution microscopy.

General description of your individual PhD-schedule:

• Your main university will be Lund University (Sweden) with Prof. Blom as supervisor.
• You will have a 6-months research secondment at Utrecht University/ University Medical Center Utrecht (Netherlands) with Prof. Rooijakkers as supervisor, where you continue to scientifically work on your thesis project.
• You will have a 1-month clinical training at Research Center Borstel Hospital (Borstel, Germany).
• You will have a 1-month entrepreneur training at MSD Finland (Helsinki).
• You will finally receive a PhD issued by Lund University and Utrecht 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. 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.

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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