PROJECT SUMMARY/ABSTRACT Malaria continues to kill more than 400,000 people yearly. Recently a group of viruses, the Matryoshka RNA viruses (MaRNAV), has been identified that is associated with the human pathogen Plasmodium vivax, and also the distantly related avian pathogen Leucocytozoon. Thus, it is clear that these viruses are ancient in their origin, but nearly nothing is known about their affects on malaria- infected hosts. We will test the hypothesis that the Matryoshka RNA viruses have a deep evolutionary history, and can affect the pathogenicity of malaria parasites. Using a bioinformatics approach, we will compare the transcriptomes of avian malaria pathogens and identify the prevalence and diversity of these viruses. We will also seek to understand how malaria infections affect specific components of the avian immune response. The proposed research is timely and significant in that it will advance the field of malaria research by providing important information about the evolution of the immune response to this common parasite. This work is innovative because birds provide the only model system where the MaRNAV viruses can be easily studied in natural populations infected by a diverse group of haemosporidian parasites. The long-term and cross-disciplinary goal of this research agenda is to elucidate the evolution of malaria pathogenicity and identify conserved viruses and immune responses that may be overlooked using mammalian model systems. The aims of the proposal are to: 1. Sequence the complete transcriptomes of select birds to determine the prevalence and diversity of malaria-associated viruses. 2. Characterize differences in immune responses between malaria- infected and non-infected avian hosts. 3. Determine whether malaria-associated viruses alter the host immune response to parasite infection. The project will support the education of future scientists through an integrative approach to research and education. It will train students in cutting edge technologies associated with infectious disease research, and provide valuable experiences for graduate and undergraduate students at an urban university serving large numbers of students traditionally underrepresented in the sciences. The developmental objectives of the PI will be met by working with outstanding collaborators, which will further his training in the molecular genetics of malaria.