MedicalResearch.com Interview with:
Manoj Duraisingh Ph.D.
John LaPorte Given Professor of Immunology and Infectious Diseases
Harvard T.H. Chan School of Public Health
Department of Immunology and Infectious Diseases
Boston, Massachusetts
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Duraisingh: The malaria parasite
P. falciparum is one of the most important pathogens of humans, with enormous mortality resulting from blood-stage infections, when parasites replicate exponentially in red blood cells. Although anti-
Plasmodial drugs are in clinical use, widespread and increasing parasite drug-resistance has contributed to an ongoing public health crisis, and we urgently need to find novel approaches to prevent and treat disease.
Targeting host red blood cell molecules presents an unexploited alternative. However, the highly differentiated and enucleated red blood cell poses a significant technical hurdle for genetic experimentation, due to the lack of a nucleus.
Here we have developed a novel, forward genetic screen to identify critical factors of malaria infection of red blood cells in an unbiased fashion. Our screen takes advantage of recent advances in human stem cell biology that enable the
ex vivo culture of red blood cells from nucleated hematopoietic precursors which are amenable to in vitro genetics.
We have now identified a surface molecule CD55 (alias Decay-Accelerating Factor, DAF) as an essential host factor required for the invasion of red blood cells by
P. falciparum. We demonstrate that this protein is required by all
P. falciparum strains tested (laboratory and field) for invasion. Furthermore, we demonstrate that CD55 acts at the initial stage of invasion when the
P. falciparum parasite attaches to the surface of the red blood cell.
Collectively, our findings indicate that CD55 is an ideal target for the development of new host-directed and vaccine therapeutics for malaria.
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