A5083391497- Malaria Research and Control
- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Biotin and Related Studies
- Vibrio bacteria research studies
- SARS-CoV-2 detection and testing
- Protein Degradation and Inhibitors
- SARS-CoV-2 and COVID-19 Research
- Cellular transport and secretion
- Complement system in diseases
- HIV/AIDS drug development and treatment
- Infection Control and Ventilation
- Synthesis and Biological Activity
- Tuberculosis Research and Epidemiology
- Biosensors and Analytical Detection
- Vector-borne infectious diseases
- Hemoglobinopathies and Related Disorders
- Aquaculture disease management and microbiota
- Protein Structure and Dynamics
- HIV Research and Treatment
- Geriatric Care and Nursing Homes
- Research on Leishmaniasis Studies
- Cancer therapeutics and mechanisms
- Drug Transport and Resistance Mechanisms
- COVID-19 epidemiological studies
The Francis Crick Institute
2017-2024
Wellcome Sanger Institute
2024
University College London Hospitals NHS Foundation Trust
2020
University College London
2016-2020
National Hospital for Neurology and Neurosurgery
2020
Birkbeck, University of London
2015-2016
Institute of Structural and Molecular Biology
2016
Significance Plasmodium malaria parasites use a unique substrate-dependent locomotion, termed gliding motility, to migrate through tissues and invade cells. Previously, it was thought that the small labile invasive stages erythrocytes, merozoites, this motility solely penetrate target erythrocytes. Here we reveal merozoites for translocation across host cells prior invasion. This forms an important preinvasion step is powered by conserved actomyosin motor regulated complex signaling pathway....
Abstract Of 250 Plasmodium species, 6 infect humans, with P. falciparum causing over 95% of 600,000 annual malaria-related deaths. Its pathology arises from host cell remodelling driven by 400 exported parasite proteins, including the FIKK kinase family. About one million years ago, a bird-infecting species crossed into great apes and single non-exported gained an export element. This led to rapid expansion 15–21 atypical, Ser/Thr effector kinases. Here, using genomic proteomic analyses, we...
Abstract Objectives (S)-Leucoxine, isolated from the Colombian Lauraceae tree Rhodostemonodaphne crenaticupula Madriñan, was found to inhibit growth of Mycobacterium tuberculosis H37Rv. A biomimetic approach for chemical synthesis a wide array 1-substituted tetrahydroisoquinolines undertaken with aim elucidating common pharmacophore these compounds novel mode(s) anti-TB action. Methods Biomimetic Pictet–Spengler or Bischler–Napieralski synthetic routes were employed followed by an evaluation...
Reverse genetics is key to understanding protein function, but the mechanistic connection between a gene of interest and observed phenotype not always clear. Here we describe use proximity labeling using TurboID site-specific quantification biotinylated peptides measure changes local environment selected targets upon perturbation. We apply this technique, which call PerTurboID, understand how Plasmodium falciparum -exported kinase, FIKK4.1, regulates function major virulence factor...
Surveillance of drug resistance and the discovery novel targets—key objectives in fight against malaria—rely on identifying resistance-conferring mutations Plasmodium parasites. Current approaches, while successful, require laborious experimentation or large sample sizes. To elucidate shared determinants antimalarial that can empower silico inference, we examined genomes 724 falciparum clones, each selected vitro for to one 118 compounds. We identified 1448 variants 128 recurrently mutated...
Malaria parasites in the blood stage express a single transmembrane transport protein for release of glycolytic end product l-lactate/H+ from cell. This transporter is member strictly microbial formate-nitrite (FNT) family and novel putative drug target. Small, drug-like FNT inhibitors potently block lactate kill Plasmodium falciparum culture. The structure (PfFNT) complex with inhibitor has been resolved confirms its previously predicted binding site mode action as substrate analog. Here,...
Malaria is a mosquito-borne disease caused by apicomplexan parasites of the genus Plasmodium. Completion parasite's life cycle depends on transmission sexual stages, gametocytes, from an infected human host to mosquito vector. Sexual commitment occurs in only small fraction asexual blood-stage and initiated external cues. The gametocyte development protein 1 (GDV1) has been described as key facilitator trigger commitment. GDV1 interacts with silencing factor heterochromatin (HP1), leading...
Plasmodium falciparum, the deadly protozoan parasite responsible for malaria, has a tightly regulated gene expression profile closely linked to its intraerythrocytic development cycle. Epigenetic modifiers of histone acetylation code have been identified as key regulators parasite's transcriptome but require further investigation. In this study, we map genomic distribution falciparum deacetylase 1 (PfHDAC1) across erythrocytic asexual cycle and find it dynamic occupancy over wide array...
Abstract Plasmodium malaria parasites are obligate intracellular protozoans that use a unique form of locomotion, termed gliding motility, to move through host tissues and invade cells. The process is substrate-dependent powered by an actomyosin motor drives the posterior translocation extracellular adhesins which in turn propel parasite forward. Gliding motility essential for tissue sporozoite ookinete stages; however, short-lived erythrocyte-invading merozoite stage has never been observed...
Abstract Malaria is a mosquito-borne disease caused by apicomplexan parasites of the genus Plasmodium. Completion parasite’s life cycle depends on transmission sexual stages, gametocytes, from an infected human host to mosquito vector. Sexual commitment occurs in only small fraction asexual blood stage and initiated external cues. The gametocyte development protein 1 (GDV1) has been described as key facilitator trigger commitment. GDV1 interacts with silencing factor heterochromatin (HP1),...
ABSTRACT Reverse genetics is key to understanding protein function, but the mechanistic connection between a gene of interest and observed phenotype not always clear. Here we describe use proximity labeling using TurboID site-specific quantification biotinylated peptides measure changes local environment selected targets upon perturbation. We apply this technique, which call PerTurboID, understand how P. falciparum exported kinase, FIKK4.1, regulates function major virulence factor malaria...
Abstract Among the ∼200 Plasmodium species that infect vertebrates, six humans. Of these, P. falciparum causes >95% of all ∼500,000 annual fatalities. Phylogenetically, belongs to Laverania subgenus, a group great apes. Common is family FIKK kinases. One million years ago, single kinase conserved in gained an export element subgenus and expanded into ∼20 atypical kinases, most which are exported host cell. The fikk genes syntenic loci across , arguing for rapid expansion controlling...
Abstract Plasmodium falciparum is a deadly protozoan parasite and the causative agent of malaria, which accounts for close to 200 million cases 400,000 deaths every year. It has been identified possess tightly regulated gene expression profile that integrally linked its timely development during intraerythrocytic stage. Epigenetic modifiers histone acetylation code have as key regulators parasite’s transcriptome. In this study, we characterize solitary class I deacetylase PfHDAC1 demonstrate...