A5109890833- HIV/AIDS drug development and treatment
- Malaria Research and Control
- RNA and protein synthesis mechanisms
- Trypanosoma species research and implications
- Enzyme-mediated dye degradation
- Biochemical and Molecular Research
- RNA modifications and cancer
- RNA Research and Splicing
- Fungal and yeast genetics research
- Toxoplasma gondii Research Studies
- Drug Transport and Resistance Mechanisms
- Enzyme Production and Characterization
- Advanced Proteomics Techniques and Applications
- HIV Research and Treatment
- Genomics and Chromatin Dynamics
- Biofuel production and bioconversion
- Microbial Metabolism and Applications
- Bacteriophages and microbial interactions
- Research on Leishmaniasis Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Bacterial Genetics and Biotechnology
- Pneumocystis jirovecii pneumonia detection and treatment
- Enzyme Structure and Function
- Parasitic Infections and Diagnostics
- Enzyme Catalysis and Immobilization
Children's Hospital of Pittsburgh
2025
Lothian Sexual Health
2021
University of Manchester
2009-2018
Institute of Science and Technology
1994-2002
University of British Columbia
2000
University of Illinois Chicago
2000
Hexham General Hospital
1993
North Tyneside General Hospital
1993
University of Oxford
1976-1982
University of California, Davis
1979-1980
Dihydropteroate synthase (H 2 Pte synthase) is the target of sulfur‐based antimalarial drugs, which are frequently used in synergistic combination with inhibitors dihydrofolate reductase folate reductase) to combat chloroquine‐resistant malaria. We have isolated H coding sequence most pathogenic human parasite Plasmodium falciparum. It forms part a longer sequence, located on chromosome 8, that also specifies 6‐hydroxymethyl‐7,8‐dihydropterin pyrophosphokinase (CH OH‐H pterin PP kinase) at...
Sulfadoxine/pyrimethamine (Fansidar) is widely used in Africa for treating chloroquine-resistant falciparum malaria. To clarify how parasite resistance to this combination arises, various lines of Plasmodium were investigate the role naturally occurring mutations target enzyme, dihydropteroate synthetase (DHPS), response sulfadoxine inhibition. An improved drug assay was employed identify a clear correlation between sulfadoxine-resistance levels and number DHPS mutations. Moreover, tight...
The selection and regulation of individual mRNAs for translation initiation from a competing pool mRNA are poorly understood processes. closed loop complex, comprising eIF4E, eIF4G PABP, its by 4E-BPs perceived to be key players. Using RIP-seq, we aimed evaluate the role in gene complex 4E-BP across entire yeast transcriptome. We find that there distinct populations with coherent properties: one contains many ribosomal protein is enriched specifically all components. This class likely...
Defining intracellular protein concentration is critical in molecular systems biology. Although strategies for determining relative changes are available, defining robust absolute values copies per cell has proven significantly more challenging. Here we present a reference data set quantifying over 1800 Saccharomyces cerevisiae proteins by direct means using protein-specific stable-isotope labeled internal standards and selected reaction monitoring (SRM) mass spectrometry, far exceeding any...
Cellular stress can globally inhibit translation initiation, and glucose removal from yeast causes one of the most dramatic effects in terms rapidity scale. Here we show that same rapid inhibition occurs during growth as levels diminish. We characterize this novel regulation showing it involves alterations within 48S preinitiation complex. In particular, interaction between eIF4A eIF4G is destabilized, leading to a temporary stabilization eIF3–eIF4G on Under such conditions, specific mRNAs...
Summary The ability to measure accurately comparative levels of protein expression after drug challenge, metabolic stress, developmental programming or other perturbation represents one the most important goals in post‐genomics malaria research. We describe here a simple and robust quantitative methodology that is ideally suited vitro experiments designed study changes proteome human parasites, lethal species Plasmodium falciparum . labelling technique we have developed uses parasite uptake...
Polymerase chain reaction amplification and DNA sequencing of the Toxoplasma gondii dihydropteroate synthase gene (dhps) identified 4 alleles among parasite populations from 32 cases human toxoplasmosis. Heterologous expression enzyme assay reveal that 3 these encode sulfadiazine (Sdz)-sensitive enzymes. The fourth, generating a highly Sdz-resistant enzyme, differs 1 other at only single residue (407) dhps. Of interest, fifth allele, found in laboratory-induced line, also another...
The dynamic ability of genomes to interact with discrete nuclear compartments appears be essential for chromatin function. However, the extent which structural proteins contribute this level organization is largely unresolved. To test links between structure and function, we evaluated how lamins a major functional compartment, nucleolus. HeLa cells compromised expression genes encoding were analyzed using high-resolution imaging pull-down assays. When lamin B1 was depleted, inhibition RNA...
Abstract The PUF family of RNA-binding proteins regulate gene expression post-transcriptionally. Saccharomyces cerevisiae Puf3p is characterised as binding nuclear-encoded mRNAs specifying mitochondrial proteins. Extensive studies its regulation COX17 demonstrate role in mRNA decay. Using integrated genome-wide approaches we define an expanded set target and quantitatively assessed the global impact loss PUF3 on using polysome profiling quantitative proteomics. In agreement with prior...
The relocalization of translationally repressed mRNAs to mRNA Processing bodies (P-bodies) is a key consequence cellular stress across many systems. P-bodies harbor degradation components and are implicated in decay, but the relative timing control poorly understood. We used MS2-GFP system follow movement specific endogenous live yeast cells after nutritional stress. It appears that bi-phasic: some present early, whereas others recruited much later concomitant with recruitment translation...
Abstract Staphylococcus aureus is a commensal and opportunist pathogen of the upper respiratory tract. The recognition pathogen-associated molecular patterns through pattern-recognition receptors crucial for eliminating microorganisms such as S. aureus. DC-SIGN (CD209) receptor that binds to broad range pathogens, promoting phagocytosis. Here we aimed study role mouse homologues DC-SIGN, CD209d/e, in methicillin-resistant (MRSA) pulmonary infection model. CD209d/e−/− wild-type C57BL/6 mice...
The antifolate combination pyrimethamine/sulphadoxine (PYR/SDX; Fansidar) is frequently used to combat chloroquine‐resistant malaria. Its success depends upon pronounced synergy between the two components, which target dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) in folate pathway. This permits clearance of parasites resistant either drug alone, but its molecular basis still unexplained. Plasmodium falciparum can use exogenous folate, normally present vivo , bypassing...
We have isolated and characterised the gene encoding glycolytic enzyme enolase (2‐phospho‐ d ‐glycerate hydrolase) from human malaria parasite Plasmodium falciparum . This was achieved using a combination of cDNA sequencing inverse‐PCR techniques. The maps to chromosome 10 parasite. also mapped two further genes, glyceraldehyde‐3‐phosphate dehydrogenase triose‐phosphate isomerase, 14. encodes protein 446 amino acids (48.7 kDa), all acid residues implicated in substrate/cofactor binding...
Translation factors eIF4E and eIF4G form eIF4F, which interacts with the messenger RNA (mRNA) 5' cap to promote ribosome recruitment translation initiation. Variations in association of eIF4F individual mRNAs likely contribute differences initiation frequencies between mRNAs. As is globally reprogrammed by environmental stresses, we were interested determining whether interactions are how this may global stress responses.Using a tagged-factor protein capture RNA-sequencing (RNA-seq)...