A5019859396- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- Extracellular vesicles in disease
- Computational Drug Discovery Methods
- Drug Transport and Resistance Mechanisms
- SARS-CoV-2 and COVID-19 Research
- COVID-19 Clinical Research Studies
- Invertebrate Immune Response Mechanisms
- vaccines and immunoinformatics approaches
- Parasites and Host Interactions
- Research on Leishmaniasis Studies
- Digital Imaging for Blood Diseases
- Trypanosoma species research and implications
- Hepatitis C virus research
- Pneumonia and Respiratory Infections
- Plant Virus Research Studies
- Genomics and Phylogenetic Studies
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- HIV/AIDS drug development and treatment
- Multiple Myeloma Research and Treatments
- Machine Learning in Bioinformatics
- Global Health and Surgery
- Ethics in Clinical Research
Kenya Medical Research Institute
2015-2025
Wellcome Trust
2010-2024
University of Oxford
2009-2024
Pwani University
2014-2024
Kema International (Netherlands)
2023
University of Cambridge
2016-2023
International Centre for Genetic Engineering and Biotechnology
2017
University of Glasgow
2009-2017
Wellcome Centre for Molecular Parasitology
2009-2013
École Polytechnique Fédérale de Lausanne
2009-2011
The role of protein phosphorylation in the life cycle malaria parasites is slowly emerging. Here we combine global phospho-proteomic analysis with kinome-wide reverse genetics to assess importance Plasmodium falciparum asexual proliferation. We identify 1177 sites on 650 parasite proteins that are involved a wide range general cellular activities such as DNA synthesis, transcription and metabolism well key processes invasion cyto-adherence. Several kinases themselves phosphorylated putative...
Abstract Background The spread of resistance to chloroquine (CQ) led its withdrawal from use in most countries sub-Saharan Africa the 1990s. In Malawi, this was followed by a rapid reduction frequency point where drug is now considered be effective once again, just nine years after withdrawal. report, polymorphisms markers associated with CQ-resistance against Plasmodium falciparum isolates coastal Kenya (Kilifi) were investigated, 1993, prior CQ, 2006, seven Changes those that occurred...
ABSTRACT We have analyzed the in vitro chemosensitivity profiles of 115 Kenyan isolates for chloroquine (CQ), piperaquine, lumefantrine (LM), and dihydroartemisinin association with polymorphisms pfcrt at codon 76 pfmdr 1 86, as well variations copy number . The median drug concentrations that inhibit 50% parasite growth (IC 50 s) were 41 nM (interquartile range [IQR], 18 to 73 nM), (IQR, 29 96 32 17 46 2 3 nM) CQ, LM, dihydroartemisinin, respectively. activity CQ correlated inversely LM ( r...
Background: Although thousands of clinical isolates Plasmodium falciparum are being sequenced and analysed by short read technology, the data do not resolve highly variable subtelomeric regions genomes that contain polymorphic gene families involved in immune evasion pathogenesis. There is also no current standard definition boundaries these regions. Methods: Using long-read sequence (Pacific Biosciences SMRT technology), we assembled annotated 15 P. isolates, ten which newly cultured...
The malaria parasite life cycle includes asexual replication in human blood, with a proportion of parasites differentiating to gametocytes required for transmission mosquitoes. Commitment differentiate into gametocytes, which is marked by activation the transcription factor ap2-g , known be influenced host factors but comprehensive model remains uncertain. Here, we analyze data from 828 children Kilifi, Kenya severe, uncomplicated, and asymptomatic infection over 18 years falling...
Abstract Malnutrition impacts approximately 50 million children worldwide and is linked to 45% of global mortality in below the age five. Severe acute malnutrition (SAM) associated with intestinal barrier breakdown epithelial atrophy. Extracellular vesicles including exosomes (EVs; 30–150 nm) can travel distant target cells through biofluids milk. Since milk-derived EVs are known induce stem cell proliferation, this study aimed examine their potential efficacy improving malnutrition-induced...
Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found NK degranulate and release IFN-γ upon stimulation with antibody-opsonized
Early identification of causal genetic variants underlying antimalarial drug resistance could provide robust epidemiological tools for timely public health interventions. Using a novel natural genetics strategy mapping candidate genes we analyzed >75,000 high quality single nucleotide polymorphisms selected from high-resolution whole-genome sequencing data in 27 isolates Plasmodium falciparum. We identified associated with susceptibility to dihydroartemisinin that implicate one region on...
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a diverse family of variant surface antigens, encoded by var genes, that mediates binding infected erythrocytes to human cells and plays key role in parasite immune evasion malaria pathology. The increased availability genome sequence data has revolutionised the study PfEMP1 diversity across multiple P . isolates. However, making functional sense genomic relies on ability infer phenotype from gene sequence. For rosetting,...
Antimalarial drug resistance is a substantial impediment to malaria control. The spread of has been described using genetic markers which are important epidemiological tools. We carried out temporal analysis changes in allele frequencies 12 over two decades changing antimalarial policy Kenya. did not detect any the validated kelch 13 (k13) artemisinin markers, nonetheless, single k13 allele, K189T, was maintained at stable high frequency (>10%) time. There distinct shift from chloroquine...
Abstract Ring-infected erythrocytes are the predominant asexual stage in peripheral circulation but rarely investigated context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis ring-infected parasite cultures samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below predefined threshold 500 parasites/μl and were treated until end...
Abstract Parasite proteins called PfEMP1 that are inserted on the surface of infected erythrocytes, play a key role in severe pathology associated with infection by Plasmodium falciparum malaria parasite. These mediate binding cells to endothelial lining blood vessels as strategy avoid clearance spleen and major targets naturally acquired immunity. is encoded large multi-gene family var . Mutually-exclusive transcriptional switching between genes allows parasites escape host antibodies. This...
<ns4:p><ns4:bold>Background</ns4:bold>: Many pathogens secrete effector molecules to subvert host immune responses, acquire nutrients, and/or prepare cells for invasion. One of the ways that are secreted is through extracellular vesicles (EVs) such as exosomes. Recently, malaria parasite <ns4:italic>P. falciparum</ns4:italic> has been shown produce EVs can mediate transfer genetic material between parasites and induce sexual commitment. Characterizing content these may improve our...
The PfEMP1 family of Plasmodium falciparum antigens play a key role in pathogenesis severe malaria through their insertion into the surface parasite infected erythrocytes, and adhesion to host cells. Previous studies have suggested that parasites expressing subclasses group A DC8, associated with malaria, may growth advantage immunologically naïve individuals. However, this idea has not been tested longitudinal studies. Here we assessed expression var genes encoding PfEMP1, sampled from...
Abstract Background Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought assess the controlled human infection (CHMI) model as a means of studying naturally acquired Kenyan adults with varying Methods analysed data from 142 three locations representing distinct endemicity (Ahero, Kilifi North and South) enrolled CHMI study Plasmodium falciparum sporozoites NF54 strain (Sanaria® PfSPZ Challenge). To identify vivo outcomes that most...
Recent advances in long read technologies not only enable large consortia to aim sequence all eukaryotes on Earth, but they also allow individual laboratories their species of interest with relatively low investment. Long embody the promise overcoming scaffolding problems associated repeats and complexity sequences, number contigs often far exceeds chromosomes may contain many insertion deletion errors around homopolymer tracts. To overcome these issues, we have implemented ILRA pipeline...
Plasmodium falciparum secretes extracellular vesicles (PfEVs) that contain parasite-derived RNA. However, the significance of secreted RNA remains unexplored. Here, we compare and intracellular from asexual cultures six P. lines. We find secretion via is not only periodic throughout intraerythrocytic developmental cycle but also highly conserved across isolates. further demonstrate phases are discernibly shifted compared to those within secreting whole parasite. Finally, transcripts genes...
Over the last decade, several protein kinases inhibitors have reached market for cancer chemotherapy. The kinomes of pathogens represent potentially attractive targets in infectious diseases. functions majority Plasmodium falciparum, parasitic protist responsible most virulent form human malaria, remain unknown. Here we present a thorough characterisation PfTKL3 (PF13_0258), an enzyme that belongs to tyrosine kinase-like kinase (TKL) group. We demonstrate by reverse genetics is essential...
Plasmodium falciparum erythrocyte membrane protein 1(PfEMP1) is a family of variant surface antigens (VSA) that mediate the adhesion parasite infected erythrocytes to capillary endothelial cells within host tissues. Opinion divided over role PfEMP1 in widespread activation associated with severe malaria. In previous study we found evidence for differential associations between defined VSA subsets and specific syndromes malaria: group A-like expression “rosetting” phenotype were impaired...
High levels of genetic diversity are common characteristics Plasmodium falciparum parasite populations in high malaria transmission regions. There has been a decline intensity over 12 years surveillance the community Kilifi, Kenya. This study sought to investigate whether there was corresponding reduction P. diversity, using msp2 as marker.Blood samples were obtained from children (< 15 years) enrolled into cohort with active weekly between 2007 and 2018 Asymptomatic infections defined...
Abstract Background Cumulative malaria parasite exposure in endemic regions often results the acquisition of partial immunity and asymptomatic infections. There is limited information on how host-parasite interactions mediate maintenance chronic symptomless infections that sustain transmission. Methods Here, we determined gene expression profiles population corresponding host peripheral blood mononuclear cells (PBMCs) from 21 children (< 15 years). We compared who were defined as...