Single cell genomics provides new insight into the biology of Malaria parasites (Plasmodium vivax and Plasmodium falciparum), including their virulence and levels of drug resistance to improve treatment and control of the disease.
The new method for isolating and genome sequencing an individual malaria parasite cell will allow scientists to improve their ability to identify the multiple types of malaria parasites infecting patients and lead to ways to design drugs and vaccines to tackle this major global killer.
Malaria parasite infections are complex and often contain multiple different parasite genotypes and even different parasite species. So when researchers take a blood sample from a malaria infected patient and look at the parasite DNA within they end up with a complex mixture that is difficult to interpret.
“Current sequencing techniques really limit our understanding of malaria parasite biology” says Ian Cheeseman, Ph.D., who led this project. “It’s like trying to understand human genetics by making DNA from everyone in a village at once. The data is all jumbled up – what we really want is information from individuals.”
To achieve a better understanding of malaria parasites – single celled organisms that infect red blood cells – the project team developed a novel method for isolating an individual parasite cell and sequencing its genome. Single cell genomics allows the separation and isolation of cells to extract and sequence individual parasite DNA and determine any differences between the parasites within an infection..
“One of the real challenges was learning how to cope with the tiny amounts of DNA involved. In a single cell we have a thousand million millionth of a gram of DNA. It took a lot of effort before we developed a method where we simply didn’t lose this,” said Nair, the first author on the work.
Their method is set to change how researchers think about infections. “One of the major surprises we found when we started looking at individual parasites instead of whole infections was the level of variation in drug resistance genes. The patterns we saw suggested that different parasites within a single malaria infection would react very differently to drug treatment” said Nair.
Unfortunately the new method is currently too expensive and demanding for routine use in the clinic, as the technology matures the applications for understanding malaria biology are vast.
The findings are revealed in a study by researchers at the Texas Biomedical Research Institute and published recently in the journal Genome Research.
The work is funded by the Texas Biomedical Forum, National Institutes of Health, a Cowles Postdoctoral Training Fellowship and the Wellcome Trust and was led by Texas Biomed’s Cheeseman with collaborators at the University of Texas Health Science Center San Antonio, Case Western Reserve University, the Cleveland Clinic Lerner Research Institute, the Shoklo Malaria Research Unit, Thailand, and the Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Malawi.
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