Malaria Parasite Genomics, Development, Drug Resistance, Pathogenesis, and host-parasite interaction

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During the year 2022-2023, we continued to focus on studying the molecular mechanisms of malaria pathogenesis and signaling pathways using Plasmodium yoelii and Plasmodium berghei parasites. It was a busy year focusing on revisions of two manuscripts, working on ongoing projects, and initiating new research projects. We have made good progress in several projects: 1. We have finished a study on the molecular mechanism of malaria-induced anemia. We submitted a manuscript describing the work to a journal. After receiving the reviewers comments on the paper, we performed many experiments to address the suggestions and comments from reviewers. The revised manuscript was submitted again. 2. We have shown that over-expression of some Olfr genes could stimulate type I interferon (INF-I) responses and increase phosphorylation levels of IRF3 and TBK1. Again, a manuscript was submitted, and we are working on additional experiments in response to the reviewers comments. 3. We are working on a new E3 ubiquitin ligase that may play an important role in parasite development and drug resistance. Due to the departure of the postdoc who worked on this project, we had to restart this project with a new postdoc a few months ago. 4. We continued to study the mouse mmp3 gene that was shown to be highly expressed in malaria parasite infections. We have generated an mmp3 knockout mouse in the CBA background and performed some experiments to study the functions of MMP3 in host immune response to malaria parasite infections. We decided to generate a second MMP3 knockout (KO) mouse in a different genetic background and have obtained new MMP3 knockout mice in C57BL/6j background. We are trying to generate homologous MMP3 KO mice currently. 5, We have sequenced and assembled the genome of another P. yoelii strain (N67C), an isogenic parasite of N67. We published the genome of N67 in 2021. We have also sequenced the mRNA from the N67 and N67C parasites to improve genome annotation. The goal is to identify genes that contribute to the different disease phenotypes between the two parasites. 6, We are working on a new project studying metabolite changes in mice after infection with four Plasmodium yoelii strains and P. berghei ANKA. The data are being analyzed for publication. We are also designing experiments to treat severe malaria based on the observations from the metabolic profiling. 7, In another new project, we performed genetic crosses of P. yoelii 17XNL and N67C, cloned parasite progenies, infected mice, and extracted RNAs from infected mice for sequencing. We would like to map and identify parasite genes that cause anemia in mice infected with the two parasites. RNA samples from mice infected with 28 progenies have been sequenced, and data are being analyzed currently. 8, We initiated a project to study the forces exerted by the parasites during ookinete and sporozoite movement through the matrix and in vivo. We have obtained some preliminary data on this project. 9, In collaboration with Dr. Xiao Yu, we finished a project studying a molecule called SHIP1 that could modulate antimalarial immunity by bridging the crosstalk between type I IFN signaling and autophagy (mBio 2023, e03512-22).