A5019826446- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- Hippo pathway signaling and YAP/TAZ
- RNA modifications and cancer
- Cancer-related gene regulation
- Bacterial Infections and Vaccines
- Prenatal Substance Exposure Effects
- Antimicrobial Peptides and Activities
- Kruppel-like factors research
- Neuroblastoma Research and Treatments
- Wnt/β-catenin signaling in development and cancer
- Bacterial biofilms and quorum sensing
- Glycosylation and Glycoproteins Research
- Neonatal Respiratory Health Research
- Inhalation and Respiratory Drug Delivery
- Skin and Cellular Biology Research
- Connective tissue disorders research
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- Chromosomal and Genetic Variations
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Receptor Mechanisms and Signaling
- Neuroscience of respiration and sleep
- Muscle Physiology and Disorders
- Developmental Biology and Gene Regulation
University of Nottingham
2012-2023
Public Health Agency
2012
Alexandria University
2012
University of Zakho
2012
Institute of Molecular Medicine
2012
University of Birmingham
2003-2011
University of Leicester
1999-2001
5-Methylcytosine (5mC) is an epigenetic modification involved in regulation of gene activity during differentiation. Tet dioxygenases oxidize 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC). Both 5fC 5caC can be excised from DNA by thymine-DNA glycosylase (TDG) followed regeneration unmodified cytosine via the base excision repair pathway. Despite evidence that this mechanism operative embryonic stem cells, role TDG-dependent demethylation...
The transmembrane receptor 'ROR2' resembles members of the tyrosine kinase family signalling receptors in sequence but its' signal transduction mechanisms remain enigmatic. This problem has particular importance because mutations ROR2 are associated with two human skeletal dysmorphology syndromes, recessive Robinow Syndrome (RS) and dominant acting Brachydactyly type B (BDB). Here we show, using a constitutive dimerisation approach, that exhibits dimerisation-induced activity C-terminal...
DNA methylation (5-methylcytosine (5mC)) patterns are often altered in cancers. Ten-eleven translocation (Tet) proteins oxidise 5mC to 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). In addition their presumptive specific biological roles, these oxidised forms of may serve as intermediates demethylation process. According several reports, 5hmC levels strongly decreased cancers; however, the distribution 5fC 5caC malignant tissue has not been...
Activation of signalling by fibroblast growth factor receptor leads to phosphorylation the attenuator human Sprouty 2 (hSpry2) on residue Y55. This event requires presence adaptor substrate (FRS2). The hSpry2 is therefore mediated an intermediate kinase. Using a SRC family kinase-specific inhibitor and mutant cells, we show that direct for kinases, including itself. via dependent upon FRS2 kinase activity. forms complex with this interaction enhanced phosphorylation. Phosphorylation required...
Interactions between commensal pathogens and hosts are critical for disease development but the underlying mechanisms switching virulent states unknown. We show that human pathogen Neisseria meningitidis, leading cause of pyogenic meningitis, can modulate gene expression via uptake host pro-inflammatory cytokines to increased virulence. This is mediated by type IV pili (Tfp) reliant on PilT ATPase activity. Two Tfp subunits, PilE PilQ, identified as ligands TNF-α IL-8 in a glycan-dependent...
Fibronectin leucine rich transmembrane (FLRT) proteins have dual properties as regulators of cell adhesion and potentiators fibroblast growth factor (FGF) mediated signalling. The mechanism by which the latter is achieved still unknown subject this investigation.Here we show that FLRT1 a target for tyrosine phosphorylation FGFR1 implicate non-receptor Src family kinase (SFK). We identify residues in cytoplasmic domain these are not direct substrates suggesting SFK may exert effects via...
Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are major bacterial agents of meningitis. They each bind the 37/67-kDa laminin receptor (LamR) via surface protein adhesins: meningococcal PilQ PorA, H. OmpP2 pneumococcal CbpA. We have previously reported that a surface-exposed loop R2 domain CbpA mediates LamR-binding. Here we identified LamR-binding regions PorA OmpP2. Using truncated recombinant proteins show binding is dependent on amino acids 171-240 91-99...
Abstract Fibroblast growth factor receptors (FGFRs) are a family of four transmembrane (TM) receptor tyrosine kinases (RTKs) which bind to large fibroblast (FGF) ligands with varying affinity and specificity. FGFR signaling regulates many physiological pathological processes in development tissue homeostasis. Understanding requires the identification partner proteins regulate function biological outputs. In this study, we employ an epitope‐tagged, covalently dimerized, constitutively...
The non-integrin laminin receptor (LAMR1/RPSA) and galectin-3 (Gal-3) are multi-functional host molecules with roles in diverse pathological processes, particularly of infectious or oncogenic origins. Using bimolecular fluorescence complementation confocal imaging, we demonstrate that the two proteins homo- heterodimerize, each isotype forms a distinct cell surface population. We present evidence 37 kDa form LAMR1 (37LRP) is precursor previously described 67 (67LR), whereas heterodimer...
5-Methylcytosine (5-mC) is an epigenetic modification associated with gene repression. Recent studies demonstrated that 5-mC can be enzymatically oxidised into 5-hydroxymethylcytosine and further 5-formylcytosine (5-fC) 5-carboxylcytsine (5-caC). 5-caC has been found in embryonic stem cells mouse pre-implantation embryos but no detectable levels of this have reported for somatic tissues to date. Whereas it suggested serve as intermediate the process active demethylation, function form...
AS (Apert syndrome) is a congenital disease composed of skeletal, visceral and neural abnormalities, caused by dominant-acting mutations in FGFR2 [FGF (fibroblast growth factor) receptor 2]. Multiple splice variants are generated through alternative splicing, including PTC (premature termination codon)-containing transcripts that normally eliminated via the NMD (nonsense-mediated decay) pathway. We have discovered soluble truncated molecule encoded PTC-containing transcript up-regulated...
Pseudomonas aeruginosa causes infections in patients with compromised epithelial barrier function. Multiple virulence factors produced by P. are controlled quorum sensing (QS) via 2-alkyl-4(1H)-quinolone (AQ) signal molecules. Here, we investigated the impact of AQs on PAO1 infection differentiated human bronchial cells (HBECs). The pqsA-E operon is responsible for biosynthesis including 2-alkyl-3-hydroxy-4-quinolones, 4-hydroxy-2-alkylquinolines, and 4-hydroxy-2-alkylquinoline N-oxides as...
Abstract Chromatin of male and female gametes undergoes a number reprogramming events during the transition from germ cell to embryonic developmental programs. Although rearrangement DNA methylation patterns occurring in zygote has been extensively characterized, little is known about dynamics modifications spermatid maturation. Here, we demonstrate that 5-carboxylcytosine (5caC) correlate with active transcription LINE-1 retroelements murine spermiogenesis. We show open reading frames...
Methylation of cytosine bases (5-methylcytosine, 5mC) occurring in vertebrate genomes is usually associated with transcriptional silencing. 5-hydroxylmethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are the recently discovered modified produced by enzymatic oxidation 5mC, whose biological functions remain relatively obscure. A number approaches ranging from biochemical to antibody based techniques have been employed study genomic distribution global content these...
Methylation of cytosine bases (5-methylcytosine, 5mC) occurring in vertebrate genomes is usually associated with transcriptional silencing. 5-hydroxylmethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC) are the recently discovered modified produced by enzymatic oxidation 5mC, whose biological functions remain relatively obscure. A number approaches ranging from biochemical to antibody based techniques have been employed study genomic distribution global content these...
Neisseria meningitidis is the most frequent cause of bacterial meningitis and one few pathogens that can breach blood-brain barrier (BBB). The 37/67 kDa laminin receptor (LamR) was previously identified as a mediating meningococcal binding to rodent human brain microvascular endothelial cells, which form part BBB. surface proteins PorA PilQ were ligands for this receptor. Subsequently, fourth extracellular loop (PorA-Loop4) LamR-binding moiety. Here, we show PorA-Loop4 targets 37 precursor...
Summary Neisseria meningitidis remains an important cause of human disease. It is highly adapted to the host – its only known reservoir. Adaptations environment include many specific interactions with molecules including iron-binding proteins, components innate and adaptive immune systems, cell surface receptors such as Epidermal Growth Factor Receptor (EGFR). Interaction meningococcus EGFR has been elucidated in some detail leads intracellular signalling cytoskeletal changes contributing...