Plasmodium parasites have exerted a huge selective force on the human host over a long period of evolution, leaving strong signatures of selection in the human genome, including numerous red blood cell disorders (e.g. sickle cell disease). Most malaria research efforts have targeted parasite proteins, but a direct focus on identifying host determinants of infection represents a novel approach for elucidating critical host-pathogen interactions.
We have developed in vitro genetic approaches for the identification of critical red blood cell genes involved in malaria infection. The differentiation of primary hematopoietic stem cells and immortalized cell-lines into reticulocytes and young erythrocytes makes the enucleated red blood cell amenable to genetic analysis, through targeted lentivirus-based methods for gene knockdown.
We have undertaken forward genetic screens to identify red blood cell determinants of various aspects of malaria infection, including invasion, growth, protein trafficking and sexual development.
Papers of interest:
Host-parasite interactions that guide red blood cell invasion by malaria parasites. (Review)
Paul AS, Egan ES, Duraisingh MT. Curr Opin Hematol. 2015 May;22(3):220-6.
A forward genetic screen identifies erythrocyte CD55 as essential for Plasmodium falciparum invasion.
Egan ES, Jiang RH, Moechtar MA, Barteneva NS, Weekes MP, Nobre LV, Gygi SP, Paulo JA, Frantzreb C, Tani Y, Takahashi J, Watanabe S, Goldberg J, Paul AS, Brugnara C, Root DE, Wiegand RC, Doench JG, Duraisingh MT. Science. 2015 May 8;348(6235):711-4.
In vitro genetic analysis of an erythrocyte determinant of malaria infection.
Bei AK, Brugnara C, Duraisingh MT. J Infect Dis. 2010 Dec 1;202(11):1722-7.