A5024868123- Radiation Therapy and Dosimetry
- DNA Repair Mechanisms
- Radiation Effects in Electronics
- Radiation Detection and Scintillator Technologies
- Advanced Radiotherapy Techniques
- Effects of Radiation Exposure
- Carcinogens and Genotoxicity Assessment
- Plant Genetic and Mutation Studies
- Ion-surface interactions and analysis
- Electron and X-Ray Spectroscopy Techniques
- DNA and Nucleic Acid Chemistry
- Integrated Circuits and Semiconductor Failure Analysis
- Graphite, nuclear technology, radiation studies
- Nuclear reactor physics and engineering
- Radiomics and Machine Learning in Medical Imaging
- Advanced biosensing and bioanalysis techniques
- PARP inhibition in cancer therapy
- Cancer therapeutics and mechanisms
- Polyomavirus and related diseases
- Image Processing and 3D Reconstruction
- Cancer Immunotherapy and Biomarkers
- Boron Compounds in Chemistry
- Digital Radiography and Breast Imaging
- Immunotherapy and Immune Responses
- Advanced Data Processing Techniques
University of Manchester
2017-2024
Manchester Academic Health Science Centre
2019-2024
The Christie NHS Foundation Trust
2019-2024
Cancer Research UK Manchester Institute
2018-2023
Miami Heart Research Institute
2018
University of Surrey
2017
Faculty (United Kingdom)
2017
Our understanding of radiation induced cellular damage has greatly improved over the past decades. Despite this progress, there are still many obstacles to fully how interacts with biologically relevant components form observable endpoints. One hurdle is difficulty faced by members different research groups in directly comparing results. Multiple Monte Carlo codes have been developed simulate induction at DNA scale, while same time various models that describe repair processes varying levels...
Abstract This paper presents the first plasmid DNA irradiations carried out with Very High Energy Electrons (VHEE) over 100–200 MeV at CLEAR user facility CERN to determine Relative Biological Effectiveness (RBE) of VHEE. damage yields were measured in dry and aqueous environments that ~ 99% total breaks caused by indirect effects, consistent other published measurements for protons photons. Double-Strand Break (DSB) yield was used as biological endpoint RBE calculation, values found be...
The cellular response to ionizing radiation continues be of significant research interest in cancer radiotherapy, and DNA is recognized as the critical target for most biologic effects radiation. Incident particles can cause initial damages through physical chemical interactions within a short time scale. Initial undergo repair via different pathways available at stages cell cycle. misrepair damage results genomic rearrangement causes mutations chromosome aberrations, which are drivers...
Abstract Ultra-high dose rate (UHDR) irradiation has been shown to have a sparing effect on healthy tissue, an known as ‘FLASH’. This studied across several radiation modalities, including photons, protons and clinical energy electrons, however, very little data is available for the of FLASH with Very High Energy Electrons (VHEE). pBR322 plasmid DNA was used biological model measure damage in response Electron (VHEE) at conventional (0.08 Gy/s), intermediate (96 Gy/s) ultra-high rates (UHDR,...
Gold nanoparticles have been proven as potential radiosensitizer when combined with protons. Initially the radiosensitization effect was attributed to physical interactions of radiation gold and production secondary electrons that induce DNA damage. However, emerging data challenge this hypothesis, supporting existence alternative or supplementary mechanisms. In work we incorporate a realistic cell model detailed geometry nanoparticle biodistribution based on experimental data. The single...
Abstract Following radiation induced DNA damage, several repair pathways are activated to help preserve genome integrity. Double Strand Breaks (DSBs), which highly toxic, have specified address them. The main used resolve DSBs Non-Homologous End Joining (NHEJ) and Homologous Recombination (HR). Cell cycle phase determines the availability of HR, but choice between in G2 phases where both HR NHEJ can operate is not clearly understood. This study compares silico models experimental data...
Monte Carlo (MC) track structure simulation tools are commonly used for predicting radiation induced DNA damage by modeling the physical and chemical reactions at nanometer scale.However, outcome of these MC simulations is particularly sensitive to adopted parameters which vary significantly across studies.In this study, a previously developed full model nuclear was describe geometry.The TOPAS-nBio toolkit investigate impact physics chemistry models as well three key (the energy threshold...
Monte Carlo based simulation has proven useful in investigating the effect of proton-induced DNA damage and processes through which this occurs. Clustering ionizations within a small volume can be related to principles nanodosimetry. For simulation, it is standard construct water determine spatial clusters. More recently, realistic geometries have been used, tracking energy depositions backbone volumes. Traditionally chromatin fiber built identically replicated throughout cell nucleus,...
This work uses Monte Carlo simulations to investigate the dependence of residual and misrepaired double strand breaks (DSBs) at 24 hours on initial damage pattern created during ion therapy. We present results from a nanometric DNA simulation coupled mechanistic model Non-Homologous End Joining, capable predicting position, complexity, repair DSBs. The is scored by calculating average number DSBs within 70 nm every DSB. show that this local DSB density, referred as cluster can linearly...
Relative Biological Effectiveness (RBE), the ratio of doses between radiation modalities to produce same biological endpoint, is a controversial and important topic in proton therapy. A number phenomenological models incorporate variable RBE as function Linear Energy Transfer (LET), though lack mechanistic description limits their applicability. In this work we take different approach, using track structure model employing fundamental physics chemistry make predictions photon induced DNA...
Track structure Monte Carlo simulations are a useful tool to investigate the damage induced DNA by ionizing radiation. These usually rely on simplified geometrical representations of subcomponents. is determined physical and physicochemical processes occurring within these volumes. In particular, backbone generally assumed result in strand breaks. can be categorized as direct (ionization an atom part molecule) or indirect (damage from reactive chemical species following water radiolysis). We...
High-energy Proton Beam Therapy (PBT) commenced in England 2018 and NHS commissions PBT for 1.5% of patients receiving radical radiotherapy. We sought expert opinion on the level provision.
Abstract Very high energy electrons (VHEE) are a potential candidate for radiotherapy applications. This includes tumours in inhomogeneous regions such as lung and prostate cancers, due to the insensitivity of VHEE inhomogeneities. study explores how range can be used perform successful vitro radiobiological studies. The ARES (accelerator research experiment at SINBAD) facility DESY, Hamburg, Germany was deliver 154 MeV both (PC3) (A549) cancer cells suspension. Dose delivered samples with...
After radiation exposure, one of the critical processes for cellular survival is repair DNA double strand breaks. The pathways involved in this response are complex nature and involve many individual steps that act across different time scales, all which combine to produce an overall behaviour. It therefore experimentally challenging unambiguously determine mechanisms how they interact whilst maintaining strict control confounding variables. In silico methods can provide further insight into...
Contrast-enhanced digital mammography (CEDM) is an alternative to conventional X-ray for imaging dense breasts. However, approaches CEDM require a double exposure of the patient, implying higher dose, and risk incorrect image registration due motion artifacts. A novel approach presented, based on hyperspectral imaging, where detector combining positional high-resolution spectral information (in this case Cadmium Telluride) used. This allows simultaneous acquisition two images required CEDM....
Mechanistic in silico models can provide insight into biological mechanisms and highlight uncertainties for experimental investigation. Radiation-induced double-strand breaks (DSBs) are known to be toxic lesions if not repaired correctly. Non-homologous end joining (NHEJ) is the major DSB-repair pathway available throughout cell cycle and, recently, has been hypothesised consist of a fast slow component G0/G1. The shown resection-dependent, requiring nuclease Artemis function. However, yet...
Gold nanoparticles (GNPs) have shown a potential as radiosensitizer in radiotherapy. The radiosensitization effect is thought to be linked the increased dose deposition around GNP. Monte Carlo simulations been implemented for calculation of distributions GNPs and used enhancement. They also imported radiobiological models predict biological endpoints. This work assessed implications different physical interaction on distribution enhancement surrounded by water under proton irradiation....
The pBR322 plasmid DNA was irradiated with 35 MeV electrons, 228 protons and 300 kVp X-rays to quantify damage make comparisons of between radiation modalities. Plasmid in a medium containing hydroxyl radical scavengers varying concentrations. This altered the amount indirect hydroxyl-mediated damage, create an environment that is more closely associated biological cell. We show increasing scavenger concentration significantly reduced post-irradiation consistently equally three At low...
The induction and repair of DNA double-strand breaks (DSBs) are critical factors in the treatment cancer by radiotherapy. To investigate relationship between incident radiation cell death through DSB many silico models have been developed. These produce use custom formats data, specific to investigative aims researchers, often focus on particular pairings damage models. In this work we a standard format for reporting evaluate combinations different, independently developed, We demonstrate...
The process of end-joining during nonhomologous repair DNA double-strand breaks (DSBs) after radiation damage is considered. Experimental evidence has revealed that the dynamics DSB ends exhibit subdiffusive motion rather than simple diffusion with rare directional movement. Traditional models often overlook long-range directed motion. To address this limitation, we present a heterogeneous anomalous model consisting fractional Brownian interchanged short periods Our sheds light on underlying...
Particle therapy is a growing cancer treatment modality worldwide. However, there still remains number of unanswered questions considering differences in the biological response between particles and photons. These questions, probing mechanisms general, necessitate experimental investigation. The "Infrastructure Proton International Research" (INSPIRE) project was created to provide an infrastructure for European research, unify research efforts on topic proton ion across Europe, facilitate...
Developments in the genome organisation field has resulted recent methodology to infer spatial conformations of directly from experimentally measured contacts (Hi-C data). This provides a detailed description both intra- and inter-chromosomal arrangements. Chromosomal intermingling is an important driver for radiation-induced DNA mis-repair. Which key biological endpoint relevance fields cancer therapy (radiotherapy), public health (biodosimetry) space travel. For first time, we leverage...