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.