The work in our group is focussed on the liver stage of the Plasmodium parasite, the causal agent of malaria. The Plasmodium parasite on infecting a mammalian host, first travels to the liver where it undergoes a massive proliferation, before then infecting red blood cells, the stage of the life cycle that leads to the pathology of the disease. Despite the enormous proliferation, the liver stage of the disease is clinically silent. In a natural situation, very few sporozoites are injected into the mammalian host and thus the liver stage is a bottleneck for the parasite. For these reasons, the liver stage is a very promising target for both drug and vaccination approaches, as to eliminate the parasite before or during liver stage development would prevent disease. The liver stage is, however relatively under-studied compared to the blood stage of the parasite, partly due to its relative inaccessibility and as challenges persist in translating many experimental techniques used in other systems and on the parasite blood stage into use on the liver stage.
For our research we employ the rodent parasite Plasmodium berghei. By infecting Anopheles stephensi mosquitoes, we produce sporozoites that can be harvested and used to infect hepatoma cells or primary hepatocytes and also for intravital microscopy of infected mouse livers. Much of our work involves microscopy, ranging from confocal microscopy analysis of immunofluorescence samples, to powerful live cell microscopy using line-scanning and spinning disc microscopes to achieve high resolution imaging and to monitor parasite development over time. To allow live imaging of the parasite within the host cell, we have a range of transgenic parasites in which fluorescent proteins are targeted to different organelles or fused to proteins of interest and can image these within host cells also expressing fluorescent proteins.
Below are some of the main questions currently under investigation in the lab:
Does host cell autophagy play a role in liver stage parasite development? Can the parasite be removed by autophagy, or conversely can the parasite even hijack host cell autophagy to gain materials necessary for development?
(Dr. Jacqueline Schmuckli, Rahel Wacker, Livia Niklaus)
During liver stage development, each invading sporozoite can proliferate to form up to 30,000 merozoites. How does the parasite manage correct packaging of organelles into the new daughter merozoites on such a huge scale?
(Dr. Rebecca Limentitakis Stanway, Gesine Kaiser)
How does the parasite mediate egress from host hepatocytes?
(Dr. Paul Burda, Bernardette Schnider, Tony Zakher)
How can dormant liver stages survive in hepatocytes?
(Dr. Reto Caldelari, Dr. Rebecca Limenitakis Stanway)
