A5026676780- Reproductive tract infections research
- Amyotrophic Lateral Sclerosis Research
- Urinary Tract Infections Management
- Neurogenetic and Muscular Disorders Research
- Pancreatic function and diabetes
- Gut microbiota and health
- Glycosylation and Glycoproteins Research
- Enzyme Structure and Function
- Advanced Proteomics Techniques and Applications
- Immune Response and Inflammation
- Monoclonal and Polyclonal Antibodies Research
- Metabolism, Diabetes, and Cancer
- interferon and immune responses
- Neuropeptides and Animal Physiology
- Alzheimer's disease research and treatments
- Parkinson's Disease Mechanisms and Treatments
- Parasitic Infections and Diagnostics
- Diabetes Treatment and Management
- Chemical Synthesis and Analysis
- Coccidia and coccidiosis research
- Mass Spectrometry Techniques and Applications
- Peptidase Inhibition and Analysis
- S100 Proteins and Annexins
- Receptor Mechanisms and Signaling
- vaccines and immunoinformatics approaches
University of Sheffield
2019-2024
Novo Nordisk (Denmark)
2006-2020
Ghent University
2009
Aarhus University
1999-2003
London South Bank University
1998
Morehouse School of Medicine
1997
University Hospital of Lausanne
1987
To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its functionality, focusing on insulin secretion, proliferation, apoptosis ER stress, with objective to assess potential screening platform identification of novel anti-diabetic drug candidates.EndoC-βH1 was transplanted into mice validation in vivo functionality. Insulin secretion evaluated cultured monolayer pseudoislets, well diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, stress responses...
It is important to understand how the disease process affects metabolic pathways in amyotrophic lateral sclerosis and whether these can be manipulated ameliorate progression. To analyse basis of defect we used a phenotypic profiling approach. Using fibroblasts reprogrammed induced astrocytes from C9orf72 sporadic cases measured production rate reduced nicotinamide adenine dinucleotides (NADH) 91 potential energy substrates simultaneously. Our screening approach identified that have distinct...
Abstract Astrocytes are highly specialised cells, responsible for CNS homeostasis and neuronal activity. Lack of human in vitro systems able to recapitulate the functional changes affecting astrocytes during ageing represents a major limitation studying mechanisms potential therapies aiming preserve health. Here, we show that induced from fibroblasts donors their childhood or adulthood display age‐related transcriptional differences functionally diverge spectrum age‐associated features, such...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving selective vulnerability of energy-intensive motor neurons (MNs). It has been unclear whether mitochondrial function an upstream driver or downstream modifier neurotoxicity. We separated genetic determinants function, including variation within the genome autosomes; from changeable factors DNA copy number (mtCN). Across three cohorts 6,437 ALS patients, we discovered that set haplotypes, chosen because they are...
Amyotrophic lateral sclerosis (ALS) is characterised by motor neuron (MN) death; however, astrocytes play a key role in disease pathogenesis. Developments the field of artificial intelligence (AI) have potential to impact drug discovery multiple ways, including rapid identification repurposing candidates. A combination natural language processing and deep learning algorithms was used generate knowledge graph based on scientific literature, omics chemical databases, other public sources with...
Chlamydia trachomatis represents a group of human pathogenic obligate intracellular and gram-negative bacteria. The genome C. D comprises 894 open reading frames (ORFs). In this study the global expression genes in A, L2, which are responsible for different chlamydial diseases, was investigated using proteomics approach. Based on silver stained two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), gels with purified elementary bodies (EB) auto-radiography 35S-labeled proteins up to...
Chlamydiae are obligate intracellular bacteria that important human pathogens. The Chlamydia genomes contain orthologues to secretion apparatus proteins from other bacteria, but only a few secreted have been identified. Most likely, effector in order promote infection. Effector cannot be identified by motif or similarity searches. As new strategy for identification of we compared 2D-PAGE profiles [35S]-labelled whole lysates infected cells purified Chlamydia. Several candidates trachomatis D...
Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by the selective progressive death of motor neurons (MNs). Understanding genetic molecular factors influencing ALS survival crucial for management therapeutics. In this study, we introduce deep learning-powered analysis framework to link rare noncoding variants survival. Using data from human induced pluripotent stem cell (iPSC)-derived MNs, method prioritizes functional using learning, links...
ABSTRACT d -Alanine is a central component of the cell wall in most prokaryotes. synthesis Escherichia coli carried out by two different alanine racemases encoded alr and dadX genes. Deletion from E. genome results -alanine auxotrophic phenotype. However, we have observed growth prototrophic phenotypic revertants during routine culturing strain. We present detailed comparison proteome transcriptome profiles auxotroph revertant Most noticeably, general upregulation genes involved methionine...
PEGylation modification has been used to improve the pharmacokinetic properties of protein-based drugs. For example, PEGylated human growth hormone (hGH) shown exhibit better profiles than unmodified hGH. Unlike chemical hGH that is difficult be controlled result in homogeneity, microbial transglutaminase (mTGase) only conjugates poly(ethelene glycol) (PEG) on glutamine-40 (Q40) and glutamine-141 (Q141) hGH, glutamine residues exposed. Yet, an mTGase can selectively conjugate PEG 1 residue...
Interferon gamma (IFN-gamma) is a potent immunomodulatory lymphokine, secreted by activated T-lymphocytes and NK-cells during the cellular immune response. Actions of IFN-gamma are mediated through binding to IFN-gamma-receptor, present on most cells, subsequent activation great magnitude responsive genes has been reported previously. Our goal identify map IFN-gamma-regulated HeLa cell proteins two-dimensional polyacrylamide gel electrophoresis with immobilized pH gradient (IPG) (2-D PAGE)...
The protein composition and N-terminal sequences of proteins in the outer membrane Chlamydia trachomatis L2 were analysed following isolation peptides using combined fractional diagonal chromatography identification by liquid tandem MS. Acetylation primary amino groups vivo generated proteolytic cleavage sites facilitated such known (MOMPs). Our results further support a proposed prediction topology MOMPs. Furthermore, previously unknown MOMP, CTL0626 (Ct372), was assigned as an MOMP with...
Peptides are of increasing interest as therapeutics in a wide range diseases, including metabolic diseases such diabetes and obesity. In the latter, peptide hormones YY (PYY) pancreatic (PP) important templates for drug design. Characteristic these peptides is that they contain C-terminal α-amidated, this amidation crucial biological function. A challenge to generate by recombinant means particularly production scale. Here, we have examined an intein-mediated approach PYY derivative larger...
The blood-brain barrier (BBB) serves as a highly intricate and dynamic interface connecting the brain bloodstream, playing vital role in maintaining homeostasis. BBB dysfunction has been associated with multiple neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS); however, of neurodegeneration is understudied. We developed an ALS patient-derived model by using cells derived from 5 patient donors carrying C9ORF72 mutations. Brain microvascular endothelial-like (BMEC-like...
Abstract: M102 is a central nervous system (CNS) penetrant small molecule electrophile which activates in vivo the NFE2-related factor 2 antioxidant response element (NRF2-ARE) pathway, as well transcription of heat-shock (HSE) associated genes. In TDP-43Q331K transgenic mouse model ALS dosed subcutaneously at 5mg/kg OD or 2.5mg/kg BD with M102, significant improvements compound muscle action potential (CMAP) amplitude hind limb muscles and gait parameters were observed 6 months age, target...
We have isolated and sequenced two cDNA clones coding for plasminogen activator inhibitor 2 (PAI-2). The was used to study the regulation of PAI-2 gene transcription by tumor-promoting phorbol ester 12-myristate 13-acetate in human histiocytic lymphoma cell line U-937. tumor promoter caused a transient, 50-fold increase transcription.
Backbone cyclic insulin was designed and prepared by reverse proteolysis in partial organic solvent of a single-chain precursor expressed yeast. The contains two loops to bridge the chains native insulin. cyclisation method uses Achromobacter lyticus protease should be generally applicable proteins with C-terminal lysine proximal N-terminal. presence ring-closing bond disulfide patterns were documented LC-MS peptide maps. shown inert towards degradation CPY, but somewhat labile chymotrypsin....
Dipeptide repeat (DPR) proteins are aggregation-prone polypeptides encoded by the pathogenic GGGGCC expansion in C9ORF72 gene, most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. In this study, we focus on role poly-GA DPRs disease spread. We demonstrate that recombinant oligomers can directly convert into solid-like aggregates form characteristic β-sheet fibrils vitro. To dissect process cell-to-cell DPR transmission, closely follow fate either their...
Disruption to protein homeostasis caused by lysosomal dysfunction and associated impairment of autophagy is a prominent pathology in amyotrophic lateral sclerosis frontotemporal dementia (ALS/FTD). The most common genetic cause ALS/FTD G4C2 hexanucleotide repeat expansion C9orf72 (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation transcripts gives rise dipeptide (DPR) proteins that have been shown be toxic may contribute disease etiology. Genetic variants TMEM106B with lobar...