Miss Annie Yang - Infection and Immunity division

Miss Annie Yang - Infection and Immunity division

Location: 
Davis Auditorium
Start Time: 
Mon, 30/05/2016 - 3:00pm
End Time: 
Mon, 30/05/2016 - 4:00pm
Cell traversal activity is critical for Plasmodium falciparum to initiate liver stage malaria

PhD Completion seminar​

Malaria is an important mosquito-borne disease that causes approximately half a million deaths per year. It is caused by parasites of the genus of Plasmodium, of which P. falciparum is the most virulent form affecting humans. While malaria is known to be a disease of the blood, the crucial first step of infection occurs in the liver. The liver is a highly protected organ with hepatocytes guarded from foreign pathogens by an array of cellular barriers. Work done in rodent malaria models identified that sporozoites overcome these host cell barriers through a process known as cell traversal. To date, several proteins have been identified to be essential for this process. However little is known about the process of cell traversal by the most virulent parasite of humans, P. falciparum. This project focuses on two proteins, named sporozoite microneme proteins essential for cell traversal 1 and 2 (SPECT1 and 2). Here, we generated P. falciparum parasites deficient in SPECT1 or SPECT2 and transmitted them through mosquitoes. Sporozoites from these knockouts failed to traverse hepatocytes and human monocyte-derived macrophages in vitro and were completely unable to establish an infection in humanized mice with chimeric livers when injected intravenously. We have also started to dissect the molecular mechanisms of traversal.