Biology subjects

Barber, B. E.

Publications and source records attributed to Barber, B. E..

5 recordsLinked to original sources

bioRxiv2026

Integrative genomics of Plasmodium knowlesi reveals parasite-intrinsic regulators of severe human malaria

To dissect parasite determinants of clinical disease severity in Plasmodium knowlesi, we performed the first integrative genome-wide association (GWAS), transcriptomic, and expression quantitative trait locus (eQTL) analysis from clinical malaria isolates. We identify distinct parasite programs associated with WHO-defined severe disease, characterized by transcriptional activation of stress-response and host-interaction pathways. In contrast, invasion-linked programs were more strongly associated with parasite burden, while immune-evasion pathways showed overlapping but distinct associations with both burden and severity. GWAS and eQTL analyses revealed genetic regulation of transcriptional states, including immune-evasion variant antigen families (SICAvar and kir) and chromatin-associated regulators. Mature gametocyte transcripts were detectable across infections, including those with low parasitaemia, indicating that transmission-stage expression occurs independently of both clinical severity and parasite density. Together, these findings show that severe P. knowlesi malaria is associated with genetically regulated parasite transcriptional programs that are not fully explained by parasite burden.

genomics↗

bioRxiv2026

Mapping the global distribution and spread of the Plasmodium vivax-associated virus MaRNAV-1

Matryoshka RNA virus 1 is a bi-segmented and single-stranded RNA virus associated with Plasmodium vivax, a cause of human malaria. Little has been uncovered about the epidemiology and ecology of this virus since its discovery in 2019. To address this, we used a combination of primary and publicly available metatranscriptomic data to map the geographic distribution and host associations of MaRNAV-1. We detected this virus throughout Southeast Asia, in parts of South America, and, for the first time, in Oceania. Despite its broad distribution, MaRNAV-1 was found exclusively in metatranscriptomes containing P. vivax, suggesting that there is a specific virus-host relationship that has shaped the evolutionary history of this virus. We were unable to estimate the emergence date of the MaRNAV-1 lineage; however, phylogeographic mapping analysis suggested that MaRNAV-1 may have radiated from Southeast Asia. Our findings have both evolutionary and public health implications and can serve as the basis for future investigations in these fields.

evolutionary biology↗

bioRxiv2025

Defining the roles of NKG7 expressed by CD4+ and CD8+ T cells during malaria

Malaria, caused by Plasmodium parasites, is a significant global health issue. CD4+ and CD8+ T cells are important for immunity against Plasmodium infections, but the specific roles of many immune-related effector molecules in T cells remain poorly defined. Here, we investigated the function of NK cell granule protein 7 (NKG7) in T cells during malaria, focusing on its role in CD4+ and CD8+ T cells in Plasmodium blood-stage responses. In a non-lethal malaria model, NKG7 played a protective role in CD4+ T cell responses, affecting pro-inflammatory T helper 1 (Th1), IL-10-producing type 1 regulatory (Tr1), and T follicular helper cell development. In a model of cerebral malaria, NKG7 was shown to have a cell-intrinsic role in CD4+ T cells for perforin and granzyme B expression, as well as the development of Tr1 cells. Human investigations involving peripheral blood mononuclear cells from volunteers participating in controlled human P. falciparum malaria infection studies, as well as endemic country patients with P. falciparum and P. vivax malaria, corroborated these findings. High NKG7 expression in T cells from Plasmodium-infected humans was observed, as well as differences in NKG7 expression based on the infecting Plasmodium species. NKG7 expression was associated with both cytotoxic and non-cytotoxic T cells, indicating varied functions following infection. These results advance our understanding about NKG7s role in T cell-mediated malaria immunity and suggest potential for targeting NKG7 to improve outcomes following Plasmodium infection.

immunology↗

bioRxiv2024

Genomic epidemiology of Plasmodium knowlesi reveals putative genetic drivers of adaptation in Malaysia.

Sabah, Malaysia, has amongst the highest burden of human Plasmodium knowlesi infection in the country, associated with increasing encroachment on the parasites macaque host habitat. However, the genomic make-up of P. knowlesi in Sabah was previously poorly understood. To inform on local patterns of transmission and putative adaptive drivers, we conduct population-level genetic analyses of P. knowlesi human infections using 52 new whole genomes from Sabah, Malaysia, in combination with publicly available data. We identify the emergence of distinct geographical subpopulations within the macaque-associated clusters using IBD-based connectivity analysis. Secondly, we report on introgression events between the clusters, which may be linked to differentiation of the subpopulations, and that overlap genes critical for survival in human and mosquito hosts. Using village-level locations from P. knowlesi infections, we also identify associations between several introgressed regions and both intact forest perimeter-area ratio and mosquito vector habitat suitability. Our findings provide further evidence of the complex role of changing ecosystems and sympatric macaque hosts in Malaysia driving distinct genetic changes seen in P. knowlesi populations. Future expanded analyses of evolving P. knowlesi genetics and environmental drivers of transmission will be important to guide public health surveillance and control strategies. Author SummaryThe zoonotic P. knowlesi parasite is an emerging, yet understudied, cause of malaria in Southeast Asia. Sabah, Malaysia, has amongst the highest burden of human P. knowlesi infection in the country, however, the region is currently understudied. Thus, we produced a collection of high-quality P. knowlesi genomes from Sabah, and in combination with publicly available data, performed an extensive population genetics analysis. Our work contributes novel insights for Plasmodium knowlesi population genetics and genetic epidemiology.

genomics↗

bioRxiv2023

Characterisation of Plasmodium vivax lactate dehydrogenase dynamics in P. vivax infections

Plasmodium vivax lactate dehydrogenase (PvLDH) is an essential enzyme in the glycolytic pathway of Plasmodium vivax. It can also be used as a diagnostic biomarker. Quantitation of plasma PvLDH has been used as a measure of P. vivax biomass in clinical studies of uncomplicated and severe vivax malaria. With the increasing importance of PvLDH in studying P. vivax diagnosis and infection, improved characterisation of the dynamics of this biomarker is important. In this study, we developed mathematical models that capture parasite and matrix PvLDH dynamics in ex vivo culture and the human host. We estimated the biological parameters using ex vivo and in vivo longitudinal data of parasitemia and PvLDH concentration collected from P. vivax-infected humans using Bayesian hierarchical inference. We found that the ex vivo and in vivo estimates of PvLDH in a parasitized red blood cell differed significantly across the asexual life cycle, with in vivo estimates at least ten-fold higher than ex vivo estimates (for example, the median estimate of intraerythrocytic PvLDH mass at the end of the life cycle was 9.4x10-3 ng in vivo vs. 5.1x10-4 ng ex vivo). We also estimated the ex vivo PvLDH half-life to be 65.3 h (95% credible interval: 60.8--70.7 h), which is approximately three times longer than the median estimate of the in vivo PvLDH half-life, 21.9 h (16.7--29.9 h). Our findings provide an important foundation to further improve quantitative understanding of P. vivax biology and facilitate the development of PvLDH-based diagnostic tools.

biophysics↗