A5076923374- Cystic Fibrosis Research Advances
- Advanced biosensing and bioanalysis techniques
- Retinal Development and Disorders
- Photoreceptor and optogenetics research
- Neonatal Respiratory Health Research
- Mitochondrial Function and Pathology
- Bacterial Genetics and Biotechnology
- Inhalation and Respiratory Drug Delivery
- Respiratory viral infections research
- Diversity and Career in Medicine
- Health and Medical Research Impacts
- Retinal Diseases and Treatments
- Pharmaceutical studies and practices
- Neuroscience and Neural Engineering
- Cell Image Analysis Techniques
- Legume Nitrogen Fixing Symbiosis
- Global Health and Surgery
- Bioinformatics and Genomic Networks
- 3D Printing in Biomedical Research
- Microbial Metabolic Engineering and Bioproduction
- Advanced Biosensing Techniques and Applications
University College London
2016-2025
Ludwig-Maximilians-Universität München
2024
The outer retina (OR) is highly energy demanding. Impaired metabolism combined with high demands are expected to cause insufficiencies that make the OR susceptible complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used calculate ATP expenditure of main energy-consuming processes in three cell types for night two different periods during day. predicted a rod dominated (perifovea) area 1.69 x 10 13...
Cystic fibrosis (CF) is a debilitating hereditary disease caused by mutations in the cystic transmembrane conductance regulator (CFTR) gene, which encodes an anion channel. Wild type-CFTR gating non-equilibrium process. After ATP binding, CFTR enters stable open state (O1 ). hydrolysis leads it to short-lived post-hydrolytic (O2 ), from channels close. Here, we use probe mechanism of VX-770, first compound directly targeting protein approved for treatment CF. D1370N and K1250R reduce or...
Abstract The outer retina (OR) is highly energy demanding. Impaired metabolism combined with high demands are expected to cause insufficiencies that make the OR susceptible complex blinding diseases such as age-related macular degeneration (AMD). Here, anatomical, physiological and quantitative molecular data were used calculate ATP expenditure of main energy-consuming processes in three cell types for night two different periods during day. predicted a rod dominated (perifovea) area 1.33 ×...
Photoreceptors (PRs) are metabolically demanding and packed at high density, which presents a challenge for nutrient exchange between the associated vascular beds tissue. Motivated by ambition to understand constraints under PRs function, in this study we have drawn together diverse physiological anatomical data order generate estimates of rates ATP production per mm 2 retinal surface area. With predictions metabolic demand companion paper, seek develop an integrated energy budget outer...
Class Ia/b cystic fibrosis transmembrane regulator (CFTR) variants cause severe lung disease in 10% of (CF) patients and are untreatable with small-molecule pharmaceuticals. Genetic replacement CFTR offers a cure, but its effectiveness is limited vivo. We hypothesized that enhancing protein levels (using codon optimization) and/or activity gain-of-function variants) would more effectively restore function to CF bronchial epithelial cells. Three different the were tested: optimized (high...
Deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel is most common cause fibrosis. The F508 residue located on nucleotide-binding domain 1 (NBD1) contact with cytosolic extensions helices, particular intracellular loop 4 (ICL4). To investigate how absence at this interface impacts CFTR protein, we carried out a mutagenesis scan ICL4 by introducing second-site mutations 11 positions cis F508del. Using an image-based...
Cellular utilization of available energy flows to drive a multitude forms cellular "work" is major biological constraint. Cells steer metabolism address changing phenotypic states but little known as how bioenergetics couples the richness processes in cell whole. Here, we outline whole-cell framework that informed by proteomic analysis and an energetics-based gene ontology. We separate metabolic supply capacity generate high-energy phosphates from representation demand built on relative...
The cystic fibrosis transmembrane conductance regulator (CFTR) is a plasma membrane anion channel that plays key role in controlling transepithelial fluid movement. Excessive activation results intestinal loss during secretory diarrheas, whereas
Abstract Photoreceptors (PRs) are metabolically demanding and packed at high density, which presents a challenge for nutrient exchange between the associated vascular beds tissue. Motivated by ambition to understand constraints under PRs function, in this study we have drawn together diverse physiological anatomical data order generate estimates of rates ATP production per mm 2 retinal surface area. With predictions metabolic demand companion paper, seek develop an integrated energy budget...
<h3>Background</h3> T cell cytotoxicity plays a crucial role in defending against cancer. It is traditionally assessed by endpoint assays with non-microscopic appliance, thus lacking temporal and visual insights into middle time ranges that live-cell imaging offers. However, conventional falls short data scale due to limited replicates per condition. Combining micro-structured slides addresses these issues. Multiple adhesion patterns enable independent progression of killing processes,...
Abstract CFTR, a plasma membrane anion channel, plays key role in controlling transepithelial fluid movement. Excessive activation results intestinal loss during secretory diarrhoeas, while CFTR mutations underlie cystic fibrosis (CF). Anion permeability depends both on how well channels work (permeation/gating) and many are present at the (reflecting folding, trafficking, metabolic stability). Recently, treatments with two drug classes targeting – one boosting ion-channel function...
Abstract Class Ia/b CFTR variants cause severe cystic fibrosis (CF) lung disease in ~10% of CF patients and are untreatable with small molecule pharmaceuticals. Genetic replacement strategies offer a potential cure for all but so far, have displayed limited efficiency vivo . We hypothesised that increasing protein abundance and/or activity introduced CFTRs would more effectively restore function to bronchial epithelial cells (CFBE) the presence sputum (CFS) than wildtype (WT)-CFTR....
Abstract Deletion of phenylalanine 508 (F508del), in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel, is most common cause (CF). F508 located on nucleotide-binding domain 1 (NBD1) contact with cytosolic extensions helices, particular intracellular loop 4 (ICL4). We carried out a mutagenesis scan ICL4 by introducing five or six second-site mutations at eleven positions cis F508del, and quantifying changes membrane proximity ion-channel function CFTR. The strongly...