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Principal Investigator: JEFFREY D DVORIN
Organization: PENNSYLVANIA STATE UNIVERSITY, THE
Fiscal Year: 2024
Award: $259,646
Funding agency: National Institute of Allergy and Infectious Diseases
Project Summary
Malaria parasites quickly amplify their numbers in both the human host and mosquito vector, with a single
parasite capable of creating dozens, hundreds, or thousands of daughter parasites. The formation of
merozoites (asexual blood stage, liver stage) or sporozoites (mosquito stage) involves the segmentation of
these daughter parasites within the bounds of the initial parasite. This segmentation process has best been
defined during schizogony in the asexual blood stage, during which the basal complex is assembled to direct
the appropriate partitioning of subcellular contents to each daughter cell. Several stable, core members of the
basal complex have been defined in both asexual and sexual stage development through complementary
experiments, but nothing is known about the composition or functions of the basal complex during the even
more complicated segmentation process involved in sporozoite budding.
Therefore, in this proposed work, we will investigate the process of sporozoite segmentation that occurs within
the Plasmodium yoelii oocyst using ultrastructural expansion microscopy, focused ion beam-scanning electron
microscopy (FIB-SEM), and proximity proteomics. This will enable three-dimensional microscopy-based
assessments across the process of sporogony that will focus on the involvement of the basal complex.
Proximity proteomics approaches will allow a cross-stage and cross-species comparison of the composition of
the basal complex, and provide a first view of how it changes over the lengthy process of sporozoite
segmentation, which takes up to 10 days in Anopheles mosquitoes.
In accomplishing this proposed work, we will advance our understanding of the cell biological processes that
underlie sporozoite budding with these complementary microscopy and proteomic approaches. Our focus on
the essential basal complex will provide the molecular landscape that is used for effective sporozoite
segmentation required to promote parasite transmission.
Terms: <3-D><3-D visualization><3-Dimensional><3-dimensional visualization><3D><3D visualization><Abscission><Anopheles><Anopheles Genus><Anophelines><Attention><Binding><Biogenesis><Biological><Biological Function><Biological Process><Blood><Blood Reticuloendothelial System><Blood erythrocyte><Cell Body><Cell Nucleus><Cell Shape><Cell membrane><Cells><Cessation of life><Complex><Culicidae><Cytokinesis><Cytoplasmic Division><Cytoplasmic Membrane><Data><Daughter><Death><Development><Disease><Disorder><Erythrocytes><Erythrocytic><Excision><Extirpation><Hepatic Cells><Hepatic Parenchymal Cell><Hepatocyte><Human><Image><In Situ><Infection><Ions><Knowledge><Life Cycle><Life Cycle Stages><Liver><Liver Cells><Malaria><Marrow erythrocyte><Mediating><Membrane><Microscopy><Midgut><Modern Man><Molecular><Molecular Interaction><Mosquitoes><Mothers><Nucleus><Oocysts><Organelles><Origin of Life><Paludism><Parasites><Plasma Membrane><Plasmodium><Plasmodium Infections><Plasmodium yoelii><Process><Production><Proteins><Proteomics><Public Health><Red Blood Cells><Red Cell><Removal><Resolution><Role><Sampling><Scanning Electron Microscopy><Shapes><Sporozoites><Structure><Surgical Removal><Transmission><Work><asexual><biologic><blood corpuscles><daughter cell><developmental><experiment><experimental research><experimental study><experiments><global health><hepatic body system><hepatic organ system><imaging><life course><member><membrane structure><plasmalemma><resection><resolutions><social role><three dimensional><three-dimensional visualization><transmission process><vector mosquito>