A5060704586- Malaria Research and Control
- Mosquito-borne diseases and control
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- Drug Transport and Resistance Mechanisms
- Research on Leishmaniasis Studies
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- HIV Research and Treatment
- Aquaculture disease management and microbiota
- Computational Drug Discovery Methods
- RNA and protein synthesis mechanisms
- Complement system in diseases
- CRISPR and Genetic Engineering
- Genomics and Phylogenetic Studies
- Heat shock proteins research
- Cancer therapeutics and mechanisms
- vaccines and immunoinformatics approaches
- Endoplasmic Reticulum Stress and Disease
- Essential Oils and Antimicrobial Activity
- Chromosomal and Genetic Variations
- Phytochemical compounds biological activities
- Advanced biosensing and bioanalysis techniques
- Bacteriophages and microbial interactions
- Alkaloids: synthesis and pharmacology
Keele University
2013-2022
University of Oxford
1999-2014
John Radcliffe Hospital
1999-2014
MRC Weatherall Institute of Molecular Medicine
2001-2005
Institute of Molecular Medicine
2000
Heidelberg University
1999
University of Würzburg
1996-1999
University of Edinburgh
1994-1999
A major cause of the paucity new starting points for drug discovery is lack interaction between academia and industry. Much global resource in biology present universities, whereas focus medicinal chemistry still largely within Open source discovery, with sharing information, clearly a first step towards overcoming this gap. But interface could especially be bridged through scale-up open physical compounds, which would accelerate finding discovery. The Medicines Malaria Venture Box...
The Plasmodium falciparum var gene family codes for a major virulence factor in this most lethal of human malaria parasites. A single protein variant type is expressed on each infected red blood cell, with antigenic variation allowing progeny parasites to escape host immune detection. control mutually exclusive expression the parasite relies situ epigenetic changes. Whether occurs at transcription initiation or post transcription, however, remains be established. Recent evidence supports...
Summary The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family of antigenically diverse proteins is expressed on the surface human erythrocytes infected with malaria parasite P. , and mediates cytoadherence to host vascular endothelium. In this report, we show that export PfEMP1 slow inefficient as it takes several hours traffic newly synthesized membrane. Upon removal by trypsin treatment, surface‐exposed population not replenished during subsequent culture indicating...
Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is expressed on the surface of infected erythrocytes where it plays a central role in both cytoadhesion and immune evasion. Switches clonal expression PfEMP1 result antigenic variation that facilitates long-term chronic infection host. The var gene family encodes variants, with transcriptional switching between different variants providing molecular basis for variation. Despite importance evasion response, little known about way...
Reversible modification of proteins through the attachment ubiquitin or ubiquitin-like modifiers is an essential post-translational regulatory mechanism in eukaryotes. The conjugation has been demonstrated to play roles growth, adaptation and homeostasis all eukaryotes, with perturbation ubiquitin-mediated systems associated pathogenesis many human diseases, including cancer neurodegenerative disorders.Here we describe use HMM search functional Pfam domains found key components pathway...
Summary The var multicopy gene family encodes Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) variant antigens, which, through their ability to adhere a variety of host receptors, are thought be important virulence factors. predominant expression single cytoadherent PfEMP1 type on an infected red blood cell, and the switching between different types evade protective antibody responses, processes controlled at transcriptional level. Contradictory data have been published timing...
Abstract Background Several electroporation protocols exist to transfect exogenous DNA into Plasmodium falciparum. To date, however, only a subjective analysis of their relative efficiencies has been reported. Methods A time-course luciferase reporter expression is used provide an objective quantitative the absolute efficiency three techniques; direct ring stage infected erythrocytes, preloading erythrocytes and novel “double-tap” protocol that combines both approaches. Results Preloading...
ABSTRACT G-quadruplexes are DNA or RNA secondary structures that can be formed from guanine-rich nucleic acids. These four-stranded structures, composed of stacked quartets guanine bases, highly stable and have been demonstrated to occur in vivo the human cells other systems, where they play important biological roles, influencing processes such as telomere maintenance, replication transcription, or, case G-quadruplexes, translation processing. We report for first time detected nuclei...
Artemisinin, a sesquiterpene lactone produced by Artemisia annua glandular secretory trichomes, is the active ingredient in most effective treatment for uncomplicated malaria caused Plasmodium falciparum parasites. Other metabolites A. or related species, particularly flavonoids, have been proposed to either act as antimalarials on their own synergistically with artemisinin enhance antimalarial activity. We identified mutation that disrupts CHALCONE ISOMERASE 1 (CHI1) enzyme responsible...
The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a key virulence factor for this species of human malarial parasite. PfEMP1 expressed on the surface infected erythrocytes (IEs) and directly mediates adhesion to variety host cells. A number other parasite-encoded proteins are similarly exported IE plasma play an indirect role in process through modification cytoskeleton formation electron dense knobs into which anchored. Analysis specific contribution knob-associated...
3-(4-Chlorophenyl)-4-substituted pyrazole derivatives were synthesised and tested for their in vitro antifungal activity. Some compounds showed very good activity against four pathogenic strains of fungi. The same exhibited an interesting the strain Mycobacterium tuberculosis H37Rv. results suggest that 1,3,4-oxadiazoles 5-pyrazolinones bearing a core scaffold may be promising antitubercular agents.
A gene ( hap ) transcribed during the intra‐erythrocytic life cycle stages of human malaria parasite Plasmodium falciparum was cloned and sequenced. It found to encode a protein belonging aspartic proteinase family but which carried replacements catalytically crucial residues in hallmark sequences contributing active site this type proteinase. Consideration is given as whether first known equivalent pregnancy‐associated glycoproteins that have been documented ungulate mammals. Alternatively,...
The particular virulence of the human malaria parasite Plasmodium falciparum derives from export parasite-encoded proteins to surface mature erythrocytes in which it resides. mechanisms and machinery for erythrocyte membrane are largely unknown. In other eukaryotic cells, cholesterol-rich microdomains or "rafts" have been shown play an important role cell surface. Our data suggest that depletion cholesterol with methyl-beta-cyclodextrin significantly inhibits delivery major factor P. protein...
Plasmodium falciparum var genes encode a diverse family of proteins, located on the surfaces infected erythrocytes, which are implicated in pathology human malaria through antigenic variation and adhesion erythrocytes to microvasculature. We have constructed complete representative telomere-to-telomere yeast artificial chromosome (YAC) contig map P. 8 for studies chromosomal organization, distribution, expression genes. Three gene loci were identified 8, two close telomeres at either end...