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Complement escape by malaria parasites

  • Full or part time
    Prof S Meri
    Prof V Fremeaux-Bacchi
  • Application Deadline
    Sunday, May 10, 2020
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

The fact that various stages of the malaria parasites can survive in human blood suggest that they are capable of escaping destruction by the host complement system. Moreover, mosquito’s midgut is also exposed to human blood during and after blood meal. We have hypothesized that the Plasmodium parasite and the Anopheles mosquito’s midgut express surface proteins that interfere with complement activation and complement-mediated cell damage. In our preliminary studies, we have identified two immune evasion mechanisms that allows the invasive sporozoite stage of the P. falciparum parasite to escape complement-mediated killing. The parasite evasion molecule has been identified and will be further characterized. In the second mechanism, another parasite protein was found to hijack the central complement component C3 and its activation product, the opsonin C3b from host blood. Here, we will study how the hijacked C3 and C3b molecules exert their inhibitory activity on complement.

Under the same topic, we have also discovered that mosquito’s midgut cells utilize an evasion mechanism to escape destruction by complement activity. It targets the alternative pathway of complement activation. Specifically, we found that the mosquito midgut epithelial cells captured factor H, a natural complement regulator, from the ingested blood. Consequently, the deposition of C3b, a key complement component, on the surface was impaired and cell death was avoided. In this project, we will analyze the mosquito’s factor H receptor and its interaction with factor H. The sporozoite and midgut proteins that mediate human complement evasion are vaccine candiodates. As vaccines they would lead to an immune response that could interfere with the interaction between the immune evasion molecules and complement. This could eventually lead to enhanced parasite killing in the case of parasite-based vaccine or to mosquito killing (when fed on the blood of the vaccinated individuals) in the case of a mosquito-based vaccine.

General description of your individual PhD-schedule:


• Your main university will be University of Helsinki (Finland) with Prof. Meri as supervisor.
• You will have a 12-months research secondment at Sorbonne University (France) with Prof. Fremeaux-Bacchi as supervisor, where you continue to scientifically work on your thesis project.
• You will have a 1-month clinical training at Tirol Kliniken Innsbruck (Austria).
• You will have a 1-month entrepreneur training at RCB (Borstel, Germany).
• You will finally receive a PhD issued by Sorbonne University and University of Helsinki if you fulfil the respective requirements.

Application


Please go to 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 (or ToR if not finished yet), Abstract of Master/MD/Diploma thesis. Selected candidates will be invited for a personal interview to Copenhagen on 30thJun/01stJul Jan2020.

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 September 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 thoroughly 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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