Malaria afflicts hundreds of millions of people, kills 0.65-1.4 million each year, and greatly impedes economic development in the developing world, especially in sub-Saharan Africa. Powerful tools for eliminating Plasmodium falciparum (Pf) from defined geographical areas would be highly effective, including long-acting vaccines and/or drugs that target the pre-erythrocytic sporozoite and liver stages of the parasite. The pre-erythrocytic stages are the ideal target because they do not cause any clinical manifestations or pathology. Thus, effective vaccines or drugs against these stages would prevent infection, and thereby prevent disease and transmission.
One of the reasons why it has been difficult to target the liver stages with new drugs and vaccines is the difficulty in culturing Plasmodium liver stages. Even when there is successful parasite invasion and development in hepatocytes, the number of parasite-infected hepatocytes as compared to uninfected hepatocytes is never greater than 5%, and generally significantly lower than 1%. In this context, the goal is to take advantage of Sanaria's unique capacity to produce aseptic, purified P. falciparum sporozoites (PfSPZ) and 3 day Pf liver stage parasites (PfLVR) in axenic culture to sequence both coding and non-coding RNAs and determine the gene expression profile of PfSPZ and PfLVR that have transformed to liver stage parasites during 3 days in axenic culture. Axenically transformed sporozoites are characterized by morphology (as they differ from salivary gland sporozoites) and the expression of early liver-stage markers such as PfEXP1 and PfHSP70. By these measures we are sure that these parasites are similar to naturally developed liver stage parasites.
Our expectation is that this work will allow us to define for first time key expression patterns and potentially new genes in this difficult to obtain, and understudied life cycle stage. We expect this to be of great interest and utility to the malaria research community. This work will provide critical new information to the community, augmenting the availability of data to support new lines of research with the aim to development novel anti-parasitic medicines and vaccines.
All Publications that use data generated and/or are supported by the Sequencing Center at JCVI should acknowledge the sponsor as: This project has been funded in whole or part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services under contract numbers N01-AI30071 and/or HHSN272200900007C.
White Paper Access
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