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The function and dynamic of cholesterol during Plasmodium liver stage infection

Objective

Plasmodium parasites are the causative agents of malaria, amongst the most prevalent and severe human infectious diseases. Liver infection by Plasmodium sporozoites is the first obligatory step of malaria and a quite attractive target for prophylactic strategies against the disease. At this stage, each sporozoite invades a single hepatocyte and develops into thousands of merozoites that are released into the bloodstream. Preliminary results of the host laboratory clearly show that a hepatocyte receptor, SR-BI, plays a crucial role both in invasion and development of Plasmodium in the liver. In its physiological role, SR-BI is a central component of the cholesterol uptake by cells. Thus, the overall aim of this project is to reveal whether and how cholesterol uptake by SR-BI is critical for hepatocyte infection by Plasmodium. By using various cell biology approaches, we propose to: 1) describe the chronology of cholesterol requirements during the infection, 2) investigate the SR-BI and cholesterol organization and dynamic at the sporozoite-host cell interphase and 3) determine the role of SR-BI in delivering cholesterol for Plasmodium development inside hepatocytes. Achieving this plan of work will, hopefully, provide a rationale for a potential SR-BI/cholesterol-based anti-malarial prophylactic intervention, and contribute to the European excellence by reaching one of the main goals of the 7th Framework Programme regarding Action to Confront Infectious Diseases.
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Coordinator

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES

Address

Avenida Prof Egas Moniz
1649 028 Lisboa

Portugal

Activity type

Research Organisations

EU Contribution

€ 148 048,66

Administrative Contact

Margarida Pinto Gago (Dr.)

Project information

Grant agreement ID: 235864

Status

Closed project

  • Start date

    22 April 2009

  • End date

    21 April 2011

Funded under:

FP7-PEOPLE

Coordinated by:

INSTITUTO DE MEDICINA MOLECULAR JOAO LOBO ANTUNES

Portugal