November 18, 2011
Research at the Harvard School of Public Health that could play a key role in the development of a new malaria drugs has received new funding from the Bill & Melinda Gates Foundation. The work could also lead to new vaccines to fight the killer disease.
Malaria kills roughly one million people each year, mostly children under age five in sub-Saharan Africa. Currently no licensed vaccine is available.
Gates “Grand Challenges Explorations” funding supports creative, high-risk concepts with the potential to develop solutions to difficult global health problems. The research by associate professor of immunology and infectious diseases Manoj Duraisingh, conducted in collaboration with the Broad Institute, uses novel methods to identify all of the genes in red blood cells that are essential for the malaria parasite to survive. Duraisingh hopes to identify those genes most likely to respond to drug therapies.
Duraisingh’s project, which will receive nearly $833,000 over two years, is one of nine being funded by Grand Challenges Explorations Phase II grants.
Duraisingh explained that most anti-malaria efforts have focused on attacking the malaria parasite itself. “But the parasite always finds a way around the intervention,” he said. “So we thought, instead of targeting the parasite, let’s target something in the host.”
The host is the red blood cell. Duraisingh and colleagues set out to find the key proteins in those cells that the malaria parasite needs to survive. But finding these proteins requires genetic analysis. Such analysis requires a nucleus—and red blood cells lack nuclei.
To skirt this roadblock, Duraisingh made use of the stem cells found in bone marrow. These cells, which have nuclei, eventually morph into red blood cells, at which point they shed their nuclei. But, in the lab, Duraisingh manipulated the stem cells to create “mutant” cells with nuclei that look like normal red blood cells to the malaria parasite, but which, in their new form, were able to be genetically analyzed.
So far, Duraisingh and his colleagues have used the new method to identify one protein in red blood cells involved in malaria infection. Over the next two years, with the Gates funding, they will identify all of the proteins that play a crucial role in supporting the malaria parasite, thus creating a “blueprint” of all the genes that could be potential targets for anti-malarial drugs.
Duraisingh’s work also plays a key role in new research from the Wellcome Trust Sanger Institute, published online in the journal Nature November 9, 2011, that suggests a promising focus for vaccine development. That paper reveals that the malaria parasite relies on a single receptor on the red blood cell’s surface in order to survive. The research relied on Duraisingh’s new approach to red blood cell genetics to validate the single receptor.
Dyann Wirth, chair of the Department of Immunology and Infectious Diseases, said that Duraisingh’s research “offers a whole new avenue for understanding an intervention for malaria.”
–Karen Feldscher
Learn more
New Twist on Potential Malaria Drug Target Acts by Trapping Parasites in Cells (HSPH release)