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NIH Funds Research to Sequence Malaria Parasite Transcriptome, Proteome

This story has been updated to provide additional information about the mouse model used in the study.

NEW YORK (GenomeWeb) - The National Institutes of Health's National Institute of Allergy and Infectious Disease has awarded $216,632 in funding to a team of researchers who want to sequence the transcriptome and proteome of Plasmodium vivax.

P. vivax is one of five human malaria parasites that commonly infect humans, and while it is not one of the deadliest strains of malaria, it has been linked to severe disease and death. However, P. vivax is one of the malaria parasites that have been understudied. 

Led by Liwang Cui, an associate professor at Pennsylvania State University, the investigators state in their project proposal that "research on P. vivax malaria has lagged significantly behind, largely due to the lack of a continuous in vitro culture system. This parasite selectively invades reticulocytes, making long-term culture difficult."

However, the researchers said they have found a way to overcome the difficulties with growing P. vivax cells in culture by using a humanized mouse model. Stefan Kappe, an affiliate professor with the University of Washington's Department of Global Health not involved in the study, was one of the first researchers to modify the humanized mouse model to research infectious diseases that are often difficult to study in culture, including several human malaria parasites.

Thus far researchers have only been able to obtain limited amounts of information about the parasite's asexual erythrocytic cycle or the development biology of P. vivax gametocytes, making it impossible to complete a full transcriptome and proteome analysis of P. vivax malaria. Cui et al.'s model uses a humanized mouse, or a very immunocompromised mouse, and injects that mouse with human parasites. Since the humanized mouse is severely immunocompromised it does not reject grafted human hepatocytes (liver cells) and human red blood cells, both of which are required in order to infect the mouse with human malaria parasites, which makes this model an ideal way to study the disease in different stages of its development.

The humanized mouse makes it possible to study the whole life cycle of the parasite, Deirdre Joy, the project contact at NIAID for the study, told GenomeWeb. This is key for P. vivax, since many stages of the life cycle have not been observable through attempts at cell culture, which usually die-off after a couple of days.

In addition to getting more information about the parasites' gametocyte developmental biology and asexual system, the researchers also plan to focus on what is happening in one of the parasite's dormant stages in the liver.

The investigators believe that they will be able to generate comprehensive transcriptomic and proteomic data that will give insight into the fundamental biology of asexual and sexual development of P. vivax. They also stated in their proposal that the data generated will be "critical for the discovery of novel drugs and vaccines for the interruption of P. vivax transmission." 

While the humanized mouse model isn't new, using it to overcome the technology hurdle to gain insight into P. vivax gametocytes is potentially a technological advance that could help scientists overcome difficulties with growing in vitro cultures in other instances, Joy said, adding that other teams are already starting to use the humanized mouse model to look into drug resistance and genetic crosses

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