Biology subjects

Kemp, A.

Publications and source records attributed to Kemp, A..

7 recordsLinked to original sources

bioRxiv2025

Characterisation of Two Plasmodium Virulence Factors Important for Lipid Metabolism and Disease Progression In Vivo

Malaria is caused by Plasmodium parasites and claims 610,000 deaths annually. Parasite invasion of red blood cells (RBCs) involves secretion of multiple proteins from specialised apical organelles (micronemes, rhoptries, and dense granules). These collectively facilitate host cell entry, establish a protective parasitophorous vacuole (PV), and directly and indirectly mediate interactions between the infected RBC (iRBC) and the endothelial wall. The cytoadherence of iRBCs results in sequestration within organs and plays a critical role in pathogenesis and virulence, but the function of many secreted parasite proteins remains poorly characterised. Here, we leverage spatial proteomics from Plasmodium falciparum to identify two novel Plasmodium berghei orthologue proteins containing hydrolase domains (MAP1, PBANKA_1425900, and RhoSH, PBANKA_1001500). Ultrastructure expansion microscopy reveals their localisation to the rhoptries in late schizogony, where co-immunoprecipitation assays show they interact with each other. In vivo studies demonstrate that these proteins help the parasite evade spleen-mediated clearance and contribute to disease progression. Deletion of both genes disrupts lipid metabolism and PV membrane morphology, suggesting a role in establishing or maintaining the protective PV membrane. Loss of map1 reduces sequestration of P. berghei iRBCs to adipose tissue, and conditional knockdown of the P. falciparum map1 orthologue results in reduced CD36-mediated cytoadhesion, suggesting a cross-species role in sequestration and cytoadherence. Our findings identify MAP1 and RhoSH as key mediators of Plasmodium virulence.

microbiology↗

bioRxiv2025

The spatial proteome of the Plasmodium falciparum schizont illuminates the composition and evolutionary trajectories of its organelles

Malaria is caused by apicomplexan parasites of the genus Plasmodium, with all malaria symptoms and pathology caused by parasite stages that develop within, or transit between, host erythrocytes. The ability of Plasmodium cells to parasitise erythrocytes depends on distinctive intracellular compartments associated with invasion, as well as the development of unique cellular niches within the infected host cell. However, our understanding of the biology of the malaria parasite is limited by the fact that a large proportion of the parasites proteome has no known cellular location or function. To address this problem, we have generated comprehensive high-resolution maps of protein subcellular localisation for the invasive stage of the erythrocytic life cycle of Plasmodium falciparum, the major cause of malaria mortality. Using the spatial proteomics technique hyperplexed Localisation of Organelle Proteins by Isotopic Tagging (hyperLOPIT) we generated data for 3000 P. falciparum proteins expressed in late schizont stages. Our hyperLOPIT data resolved 24 distinct cellular niches, and using supervised machine-learning we can classify 1646 proteins into one of these compartments including exported sites within the host cell. Through comparative genomic analyses our data resolve the spatial patterns of cell evolution that have shaped the development of Plasmodium species and ongoing adaptive pressures and responses that challenge our efforts to manage these major disease-causing organisms.

microbiology↗

bioRxiv2025

Plasmodium falciparum Myosin F with a Rab-like tail domain localises to perinuclear membranes and associates with trafficking proteins

Members of the myosin superfamily are found in all eukaryotes, including Plasmodium falciparum, the parasite that causes malaria. Plasmodium falciparum expresses six myosins, but apart from PfMyoA, these motors remain largely uncharacterised. This includes the class XXII myosin PfMyoF. Here, we characterise PfMyoF using structural prediction tools, biochemical assays, and advanced imaging. We show that PfMyoF is a plus-end directed, processive motor with a long neck domain containing six IQ motifs that bind the calmodulin homologue PfCaM. PfMyoF can dimerise and is predicted to adopt an autoinhibited conformation via tail backfolding. The PfMyoF tail contains a Rab-like domain that has not been identified in any other known class of myosin. Pull-down experiments show interactions between endogenous PfMyoF and trafficking proteins, including the vesicle marker PfRab18. Expansion and immunoelectron microscopy reveal that PfMyoF localises to a perinuclear membrane compartment. Our findings define PfMyoF as the first known myosin with a Rab-like domain and highlight its potential role in parasite membrane trafficking pathways.

molecular biology↗

bioRxiv2025

A Descriptive Study of wetland vegetation, ecology, habitat and Rift Valley Fever virus vectors in South Africa.

Outbreaks of Rift Valley fever (RVF) have been closely linked to environmental conditions that support large vector populations with what is required for breeding of vectors. Fine-scale vegetation surveys were used to assess how wetland plant communities vary across sites with historical RVF outbreaks in Free State Province of South Africa and to detail plant species density that correlates with mosquito habitat. MethodsAt 22 sites, we compiled 201 releves using the modified Braun-Blanquet method in combination with 200 transects using the line-point method developed specifically for this study. A total of 195 plants were identified and vouchered. These data were combined with soil analyses carried out at all 22 sites and with data from bimonthly mosquito trapping at all sites. Results and significanceWe identified an increase of invasive plants and upland species compared to the earlier study and observed that drought causes a change in wetland vegetation community structure and species composition. However, the wetland vegetation was still dominated by grasses and sedges, with a limited presence of Juncus and forbs. Livestock grazing pressure on wetlands to the drought results in reduced vegetation cover, abundance and diversity. Our work describes a changing landscape that may impact RVFV maintenance and transmission, and provides insights into extensive livestock farming and rainfall over shallow endorheic depressions in temperate grasslands and subtropical riparian environments.

ecology↗

bioRxiv2024

Optical tweezers reveal that PfEBA and PfRH ligands, not PfMSP1, play a central role in Plasmodium-falciparum merozoite-erythrocyte attachment

Malaria pathogenesis and parasite multiplication both depend on the ability of Plasmodium falciparum merozoites to invade human erythrocytes. Invasion is a complex multi-step process that is known to involve multiple P. falciparum proteins but dissecting the precise role of individual proteins has to date been limited by the availability of quantifiable phenotypic assays. In this study, we apply a new approach to assigning function to invasion proteins by using optical tweezers to directly manipulate recently egressed merozoites and erythrocytes and quantify the strength of attachment between them, as well as the frequency with which such attachments occur. Using a range of inhibitors, antibodies, and genetically modified P. falciparum strains, we quantitated the contribution of individual P. falciparum proteins to these merozoite-erythrocyte attachment phenotypes for the first time. Most of the interactions investigated did not affect the force needed to pull merozoites and erythrocytes apart, including loss of the major P. falciparum merozoite surface protein PfMSP1 and PfGAP45, part of the glideosome actinomyosin motor complex. The only factors that significantly reduced the strength of merozoite-erythrocyte attachment were ones that disrupted the function of members of the EBA-175 like Antigen (PfEBA) family and Reticulocyte Binding Protein Homologue (PfRH) invasion ligand families. While these assays also reinforced the known redundancy within these families, with the deletion of some ligands not impacting detachment force, it appears that the PfEBA/PfRH families play a central role in merozoite attachment, not the major merozoite surface protein PfMSP1. Author summaryMalaria is a devastating disease caused by a parasitic infection. The deadliest species is Plasmodium falciparum, which causes more than 600,000 deaths annually. The parasites life cycle is complex, but all the symptoms of malaria are caused when the parasites replicate in human red blood cells. Replication depends on the invasion of the red blood cells by the parasites which is a complex process involving multiple molecular interactions and multiple steps. Invasion begins with the attachment of the parasite to the red blood cell, making this step of particular interest in the development of new therapeutics. We assessed which interactions are key to the strength of attachment using an optical tweezer assay, which allowed us to directly measure the binding force between individual parasites and red blood cells whilst using a range of molecular and genetic tools that target specific interactions known to have a role in invasion. This showed that loss of a protein commonly thought to be critical to the early stages of binding (PfMSP1) had no effect on attachment strength, whereas disruptions of several members from two families of proteins (the Erythrocyte Binding Like protein family and the reticulocyte binding-like protein family) affect attachment strength.

molecular biology↗

bioRxiv2023

Localized Rift Valley Fever Virus Persistence Depends on a High Transovarial Transmission Fraction

Rift Valley fever virus (RVFV) has spread beyond continental Africa and threatens to follow West Nile, chikungunya and Zika viruses into the Americas. Its impact in new localities and the capacity to control future outbreaks, depends on whether and how RVFV persists at small spatial scales. Transovarial transmission (TOT) is hypothesized as an important mechanism for local persistence, yet its role in RVFV ecology remains poorly understood. We examine whether RVFV can persist locally via TOT while maintaining a realistic seroprevalence pattern of interepidemic and epidemic transmission. We developed a mechanistic, compartmental model of RVFV dynamics within a single host (sheep) and two vector (mosquito) populations, driven by temperate climatic factors. Decades-long persistence was possible in our simulations, which generally captured the observed outbreak patterns in central South Africa with a mean annual seroprevalence ([~]23%) within the range reported during interepidemic periods (5-40%). Persistence was only possible with a substantial TOT fraction and over a narrow range of parameters. The basic reproduction number (R0) was close to one at mean vector population sizes, suggesting a relatively limited expansion of the infected vector population during outbreaks. This limited expansion provides the system with the flexibility to support both low-level transmission and large outbreaks and, counterintuitively, large outbreaks resulted in smaller infected Aedes egg populations. This has important consequences for control: low-level vaccination may prevent large outbreaks without eliminating RVFV and local control efforts may be most effective immediately following an outbreak, suggesting elimination may be possible after emergence in temperate regions.

ecology↗

bioRxiv2021

Effects of Task Demands on Neural Correlates of Acoustic and Semantic Processing in Challenging Listening Conditions

PurposeListeners shift their listening strategies to prioritize lower-level acoustic information and higher-level semantic information in challenging listening conditions. However, the neural mechanisms underlying different strategies are unclear. The current study examined the extent to which encoding of lower-level acoustic cues is modulated by task demand and relationships with the higher-level semantic processing. MethodElectroencephalography (EEG) was acquired while participants listened to sentences in noise that contained either higher or lower probability final words. Task difficulty was modulated by time available to process responses. Cortical tracking of speech - neural correlates of acoustic temporal envelope processing - were estimated using temporal response functions (TRFs). ResultsTask difficulty did not affect cortical tracking of temporal envelope of speech under challenging listening conditions. No correlations were observed between the cortical tracking of temporal envelope of speech and semantic processes, even after controlling for the effect of individualized signal-to-noise ratios. ConclusionsCortical tracking of temporal envelope of speech and semantic processing are differentially influenced by task difficulty. While increased task demands modulated higher-level semantic processing, cortical tracking of temporal envelope of speech may be influenced by task difficulty primarily when the demand is manipulated in terms of acoustic properties of the stimulus, consistent with an emerging perspective in speech perception.

neuroscience↗