| 1. |
- Raddi, Gianmarco, et al.
(författare)
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Mosquito cellular immunity at single-cell resolution
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 369:6507, s. 1128-1132
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Tidskriftsartikel (refereegranskat)abstract
- Hemocytes limit the capacity of mosquitoes to transmit human pathogens. Here we profile the transcriptomes of 8506 hemocytes of Anopheles gambiae and Aedes aegypti mosquito vectors. Our data reveal the functional diversity of hemocytes, with different subtypes of granulocytes expressing distinct and evolutionarily conserved subsets of effector genes. A previously unidentified cell type in An. gambiae, which we term “megacyte,” is defined by a specific transmembrane protein marker (TM7318) and high expression of lipopolysaccharide-induced tumor necrosis factor–α transcription factor 3 (LL3). Knockdown experiments indicate that LL3 mediates hemocyte differentiation during immune priming. We identify and validate two main hemocyte lineages and find evidence of proliferating granulocyte populations. This atlas of medically relevant invertebrate immune cells at single-cell resolution identifies cellular events that underpin mosquito immunity to malaria infection.
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| 2. |
- Chiappino-Pepe, Anush, et al.
(författare)
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Genome reconstructions of metabolism of Plasmodium RBC and liver stages
- 2021
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Ingår i: Current Opinion in Microbiology. - : Elsevier. - 1369-5274 .- 1879-0364. ; 63, s. 259-266
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Forskningsöversikt (refereegranskat)abstract
- Genome scale metabolic models (GEMs) offer a powerful means of integrating genome and biochemical information on an organism to make testable predictions of metabolic functions at different conditions and to systematically predict essential genes that may be targeted by drugs. This review describes how Plasmodium GEMs have become increasingly more accurate through the integration of omics and experimental genetic data. We also discuss how GEMs contribute to our increasing understanding of how Plasmodium metabolism is reprogrammed between life cycle stages.
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| 3. |
- Hillier, Charles, et al.
(författare)
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Landscape of the Plasmodium Interactome Reveals Both Conserved and Species-Specific Functionality
- 2019
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Ingår i: Cell Reports. - : Elsevier. - 2211-1247. ; 28:6, s. 1635-1647
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Tidskriftsartikel (refereegranskat)abstract
- Malaria represents a major global health issue, and the identification of new intervention targets remains an urgent priority. This search is hampered by more than one-third of the genes of malaria-causing Plasmodium parasites being uncharacterized. We report a large-scale protein interaction network in Plasmodium schizonts, generated by combining blue native-polyacrylamide electrophoresis with quantitative mass spectrometry and machine learning. This integrative approach, spanning 3 species, identifies > 20,000 putative protein interactions, organized into 600 protein clusters. We validate selected interactions, assigning functions in chromatin regulation to previously unannotated proteins and suggesting a role for an EELM2 domain-containing protein and a putative microrchidia protein as mechanistic links between AP2-domain transcription factors and epigenetic regulation. Our interactome represents a high-confidence map of the native organization of core cellular processes in Plasmodium parasites. The network reveals putative functions for uncharacterized proteins, provides mechanistic and structural insight, and uncovers potential alternative therapeutic targets.
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