A5050585535- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Advanced biosensing and bioanalysis techniques
- Lipid Membrane Structure and Behavior
- Nanoparticle-Based Drug Delivery
- Antimicrobial Peptides and Activities
- Virus-based gene therapy research
- Calcium signaling and nucleotide metabolism
- Retinal Development and Disorders
- Glycosylation and Glycoproteins Research
- Nanoplatforms for cancer theranostics
- Synthesis and Characterization of Heterocyclic Compounds
- Immunotherapy and Immune Responses
- Click Chemistry and Applications
- Cell death mechanisms and regulation
- Autophagy in Disease and Therapy
- Biochemical and Structural Characterization
- Synthesis and biological activity
- Monoclonal and Polyclonal Antibodies Research
- Gold and Silver Nanoparticles Synthesis and Applications
- Advanced Fluorescence Microscopy Techniques
- Extracellular vesicles in disease
- Environmental DNA in Biodiversity Studies
- Photochromic and Fluorescence Chemistry
- Signaling Pathways in Disease
Joint Research Centre
2019-2025
Cardiff University
2015-2024
Lancaster University
2022
Newcastle University
2021
Age UK
2021
V.V. Dokuchaev Soil Science Institute
2014
University of Portsmouth
2012
Japan Science and Technology Agency
2005-2008
Kyoto University
2005-2008
Kyoto University Institute for Chemical Research
2005-2008
The use of membrane-permeable peptides as carrier vectors for the intracellular delivery various proteins and macromolecules modifying cellular function is well documented. Arginine-rich peptides, including those derived from human immunodeficiency virus 1 Tat protein, are among representative classes these vectors. internalization mechanism vector their protein conjugates was previously regarded separate endocytosis, but more recent reevaluations have concluded that endocytosis involved in...
Nonviral gene complexes can enter mammalian cells through different endocytic pathways. For efficient optimization of the carrier it is important to profile its cellular uptake, because this largely determines intracellular processing and subsequent transfection efficiency. Most current information on uptake these gene-delivery vehicles based data following use chemical inhibitors Here, we have performed a detailed characterization four commonly used endocytosis [chlorpromazine, genistein,...
The exact mechanisms by which arginine-rich cell-penetrating peptides enter cells are still the subject of debate. Here, we have analyzed in detail effects serum and extracellular concentration on internalization oligoarginines (R n; n = 4, 8, 12, 16). presence incubation medium had a major influence uptake R12 R16 but did not affect R4 R8 significantly. Incubation at 37 degrees C with serum-containing showed that majority labeling was confined to punctate endocytic structures. Performing...
In order to engineer safer nanomaterials, there is a need understand, systematically evaluate, and develop constructs with appropriate cellular uptake intracellular fates. The overall goal of this project determine the patterns silica nanoparticle geometries in model cells, aid identification role geometry on transport. our experiments we observed significant difference viability two phenotypes primary macrophages; immortalized macrophages exhibited similar patterns. However, both epithelial...
Abstract Protein therapy holds great promise for treating a variety of diseases. To act on intracellular targets, therapeutic proteins must cross the plasma membrane. This has previously been achieved by covalent attachment to cell-penetrating peptides (CPPs). However, there is limited information relative performance CPPs in delivering cells, specifically cytosol and other locations. Here we use green fluorescent protein (GFP) as model cargo compare delivery capacity five CPP sequences...
Delineating the mechanisms by which cell-penetrating peptides, such as HIV-Tat peptide, oligoarginines and penetratin, gain access to cells has recently received intense scrutiny. Heightened interest in these entities stems from their ability enhance cellular delivery of associated macromolecules, genes proteins, suggesting that they may have widespread applications drug-delivery vectors. Proposed uptake include energy-independent plasma membrane translocation energy-dependent vesicular...
A major unmet clinical need is a universal method for subcellular targeting of bioactive molecules to lysosomes. Delivery this organelle enables either degradation oncogenic receptors that are overexpressed in cancers, or release prodrugs from antibody–drug conjugates. Here, we describe general uses receptor crosslinking trigger endocytosis and subsequently redirect trafficking receptor:cargo complexes their expected route, By incubation plasma membrane with biotinylated cargo subsequent...
Prostate cancer EVs remain differentiation competent when fluorescently labelled using a novel thiol-based method, allowing exploration of their endocytosis and trafficking.
Abstract Land degradation is the persistent reduction in capacity of land to support human and other life on Earth (IPBES, 2018). This process jeopardizes provision ecosystem services. The Sustainable Development Goal (SDG) 15, ‘Life Land’, includes efforts sustainably manage recover natural ecosystems restore degraded soil. Under umbrella SDG United Nations Convention Combat Desertification (UNCCD) has defined an indicator framework monitor progress toward ‘land neutrality’. We evaluated...
Soil eukaryotes play a crucial role in maintaining ecosystem functions and services, yet the factors driving their diversity distribution remain poorly understood. While many studies focus on some eukaryotic groups (mostly fungi), they are limited spatial scale. Here, we analyzed an unprecedented amount of observational data soil eukaryomes at continental scale (787 sites across Europe) to gain further insights into impact wide range environmental conditions (climatic edaphic) community...
Rab proteins comprise a family of monomeric GTPases that control cellular membrane traffic. Rab21 is poorly characterised member with no known function. Human cDNA from K562 cells was subcloned into GFP expression vectors to generate and mutants defective in either GTP hydrolysis (Rab21 Q78L) or binding T33N) for transfection studies HeLa cells. Confocal fluorescence microscopy ultrastructural revealed be predominantly localised the early endocytic pathway, on vesicles containing...
To gain a better understanding of intracellular processing nanomedicines, we employed quantitative live-cell fluorescence colocalization microscopy to study endosomal trafficking polyplexes in retinal pigment epithelium cells. A new, dynamic algorithm was developed, based on particle tracking and trajectory correlation, allowing for spatiotemporal characterization internalized comparison with compartments labeled EGFP constructs. This revealed early the specifically Rab5-...
Abstract Poor understanding of intracellular delivery and targeting hinders development nucleic acid‐based therapeutics transported by nanoparticles. Utilizing a siRNA‐targeting small molecule profiling approach with advanced imaging machine learning biological insights is generated into the mechanism lipid nanoparticle (MC3‐LNP) mRNA. This workflow termed Advanced Cellular Endocytic for Intracellular Delivery (ACE‐ID). A cell‐based assay perturbation 178 targets relevant to trafficking used...