Christopher Dunsby
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View article: A Plastic EMP1 <i>+</i> to LGR5 <i>+</i> Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer
A Plastic EMP1 <i>+</i> to LGR5 <i>+</i> Cell State Conversion as a Bypass to KRASG12D Pharmacologic Inhibition in Metastatic Colorectal Cancer Open
Inhibitors of the oncogene KRAS hold promise for treating metastatic colorectal cancer (mCRC). In this study, we show that a selective, covalent small-molecule inhibitor of the active (ON) conformation of RAS-G12D, RMC-9945, exerts durable…
View article: Cleared tissue dual-view oblique plane microscopy
Cleared tissue dual-view oblique plane microscopy Open
We present a dual-view oblique plane microscope (dOPM) for imaging thick optically cleared tissue samples using a silicone immersion primary objective. The custom-designed remote refocusing relay utilizes stock optics to achieve remote ref…
View article: Multimodal profiling unveils a reversible breast basal-like cell state in AKT-inhibitor resistant tumours
Multimodal profiling unveils a reversible breast basal-like cell state in AKT-inhibitor resistant tumours Open
The PI3K/AKT/mTOR pathway is central to cell metabolism and growth. However, pharmacological inhibition of the pathway is not uniformly effective across cancer types, or even within a single cancer model. In this study, we leverage oblique…
View article: Cleared tissue dual-view oblique plane microscopy
Cleared tissue dual-view oblique plane microscopy Open
We present a dual-view oblique plane microscope (dOPM) for imaging thick optically cleared tissue samples using a silicone immersion primary objective. The custom-designed remote refocusing relay utilizes stock optics to achieve remote ref…
View article: Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor
Assessing PARP trapping dynamics in ovarian cancer using a CRISPR-engineered FRET biosensor Open
Poly(ADP-ribose) polymerase inhibitors (PARPi) have revolutionised the treatment of ovarian high grade serous carcinoma (HGSC), especially those with defective homologous recombination. However, the emergence of resistance poses a critical…
View article: Imaging of MAP kinase dynamics reveals endocytic regulation of pulsatile signalling and network re-wiring in response to targeted therapy in EGFR-mutant non-small cell lung cancer
Imaging of MAP kinase dynamics reveals endocytic regulation of pulsatile signalling and network re-wiring in response to targeted therapy in EGFR-mutant non-small cell lung cancer Open
A better understanding of the signalling mechanisms underlying transitions from drug-sensitive to drug-tolerant states is required to overcome therapy failure. We combined single-cell biosensor imaging with functional perturbations to inve…
View article: Understanding the effects of microbubble concentration on localization accuracy in super-resolution ultrasound imaging
Understanding the effects of microbubble concentration on localization accuracy in super-resolution ultrasound imaging Open
Super-resolution ultrasound (SRUS) through localising and tracking of microbubbles (MBs) can achieve sub-wavelength resolution for imaging microvascular structure and flow dynamics in deep tissue in vivo . The technique assumes that signal…
View article: Accessible low-cost, open-source, single-shot phase imaging implemented on an openFrame-based microscope
Accessible low-cost, open-source, single-shot phase imaging implemented on an openFrame-based microscope Open
View article: Accessible low-cost, long range, optical autofocus module for open-source multiwell plate and slide scanning microscopy
Accessible low-cost, long range, optical autofocus module for open-source multiwell plate and slide scanning microscopy Open
View article: 3D Acoustic Wave Sparsely Activated Localization Microscopy With Phase Change Contrast Agents
3D Acoustic Wave Sparsely Activated Localization Microscopy With Phase Change Contrast Agents Open
Objective The aim of this study is to demonstrate 3-dimensional (3D) acoustic wave sparsely activated localization microscopy (AWSALM) of microvascular flow in vivo using phase change contrast agents (PCCAs). Materials and Methods Three-di…
View article: <i>openFrame</i>: A modular, sustainable, open microscopy platform with single‐shot, dual‐axis optical autofocus module providing high precision and long range of operation
<i>openFrame</i>: A modular, sustainable, open microscopy platform with single‐shot, dual‐axis optical autofocus module providing high precision and long range of operation Open
‘ openFrame ’ is a modular, low‐cost, open‐hardware microscopy platform that can be configured or adapted to most light microscopy techniques and is easily upgradeable or expandable to multiple modalities. The ability to freely mix and int…
View article: On the Use of Singular Value Decomposition as a Clutter Filter for Ultrasound Flow Imaging
On the Use of Singular Value Decomposition as a Clutter Filter for Ultrasound Flow Imaging Open
Filtering based on Singular Value Decomposition (SVD) provides substantial separation of clutter, flow and noise in high frame rate ultrasound flow imaging. The use of SVD as a clutter filter has greatly improved techniques such as vector …
View article: Remote-refocusing light-sheet fluorescence microscopy enables 3D imaging of electromechanical coupling of hiPSC-derived and adult cardiomyocytes in co-culture
Remote-refocusing light-sheet fluorescence microscopy enables 3D imaging of electromechanical coupling of hiPSC-derived and adult cardiomyocytes in co-culture Open
View article: Remote-refocusing light-sheet fluorescence microscopy enables 3D imaging of electromechanical coupling of hiPSC-derived and adult cardiomyocytes in co-culture
Remote-refocusing light-sheet fluorescence microscopy enables 3D imaging of electromechanical coupling of hiPSC-derived and adult cardiomyocytes in co-culture Open
Improving cardiac function through stem-cell regenerative therapy requires functional and structural integration of the transplanted cells with the host tissue. Visualizing the electromechanical interaction between native and graft cells n…
View article: Mouse Organoids imaged with Dual Oblique Plane Microscopy
Mouse Organoids imaged with Dual Oblique Plane Microscopy Open
This is a dataset to demonstrate segmenting colonies of 3D cells. The primary focus is segmenting mouse organoids images using timelapse dual oblique plane microscopy. There is also a set of data mouse embryonic stem cells imaged using spi…
View article: Mouse Organoids imaged with Dual Oblique Plane Microscopy
Mouse Organoids imaged with Dual Oblique Plane Microscopy Open
This is a dataset to demonstrate segmenting colonies of 3D cells. The primary focus is segmenting mouse organoids images using timelapse dual oblique plane microscopy. There is also a set of data mouse embryonic stem cells imaged using spi…
View article: Fast and Selective Super-Resolution Ultrasound In Vivo With Acoustically Activated Nanodroplets
Fast and Selective Super-Resolution Ultrasound In Vivo With Acoustically Activated Nanodroplets Open
Perfusion by the microcirculation is key to the development, maintenance and pathology of tissue. Its measurement with high spatiotemporal resolution is consequently valuable but remains a challenge in deep tissue. Ultrasound Localization …
View article: BUbble Flow Field: a Simulation Framework for Evaluating Ultrasound Localization Microscopy Algorithms
BUbble Flow Field: a Simulation Framework for Evaluating Ultrasound Localization Microscopy Algorithms Open
Ultrasound contrast enhanced imaging has seen widespread uptake in research and clinical diagnostic imaging. This includes applications such as vector flow imaging, functional ultrasound and super-resolution Ultrasound Localization Microsc…
View article: Super-Resolution Ultrasound Localization Microscopy of Microvascular Structure and Flow for Distinguishing Metastatic Lymph Nodes – An Initial Human Study
Super-Resolution Ultrasound Localization Microscopy of Microvascular Structure and Flow for Distinguishing Metastatic Lymph Nodes – An Initial Human Study Open
Purpose Detecting and distinguishing metastatic lymph nodes (LNs) from those with benign lymphadenopathy are crucial for cancer diagnosis and prognosis but remain a clinical challenge. A recent advance in super-resolution ultrasound (SRUS)…
View article: Robust, single-shot, optical autofocus system utilizing cylindrical lenses to provide high precision and long range of operation
Robust, single-shot, optical autofocus system utilizing cylindrical lenses to provide high precision and long range of operation Open
We present a robust, “real-time” optical autofocus system for microscopy that provides high accuracy (<230 nm) and long range (∼130 µm) with a 1.4 numerical aperture oil immersion objective lens. This autofocus can operate in a closed loop…
View article: 3D single-cell shape analysis using geometric deep learning
3D single-cell shape analysis using geometric deep learning Open
A bstract Aberrations in 3D cell morphogenesis are linked to diseases such as cancer. Yet there is little systems-level understanding of cell shape determination in 3D, largely because there is a paucity of data-driven methods to quantify …
View article: Fast and selective super-resolution ultrasound in vivo with sono-switchable nanodroplets
Fast and selective super-resolution ultrasound in vivo with sono-switchable nanodroplets Open
Perfusion by the microcirculation is key to the development, maintenance and pathology of tissue. Its measurement with high spatiotemporal resolution is consequently valuable but remains a challenge in deep tissue. Ultrasound Localization …
View article: Environmentally dependent and independent control of cell shape determination by Rho GTPase regulators in melanoma
Environmentally dependent and independent control of cell shape determination by Rho GTPase regulators in melanoma Open
In order to invade 3D tissues, cancer cells dynamically change cell morphology in response to geometric and mechanical cues in the environment. But how cells determine their shape in 3D versus 2D environments is poorly understood. Studying…
View article: Robust deep learning optical autofocus system applied to automated multiwell plate single molecule localization microscopy
Robust deep learning optical autofocus system applied to automated multiwell plate single molecule localization microscopy Open
We presenta robust, long‐range optical autofocus system for microscopy utilizing machine learning. This can be useful for experiments with long image data acquisition times that may be impacted by defocusing resulting from drift of compone…
View article: Application of direct stochastic optical reconstruction microscopy (<scp>dSTORM</scp>) to the histological analysis of human glomerular disease
Application of direct stochastic optical reconstruction microscopy (<span>dSTORM</span>) to the histological analysis of human glomerular disease Open
Electron microscopy (EM) following immunofluorescence (IF) imaging is a vital tool for the diagnosis of human glomerular diseases, but the implementation of EM is limited to specialised institutions and it is not available in many countrie…
View article: Single-shot phase contrast microscopy using polarisation-resolved differential phase contrast
Single-shot phase contrast microscopy using polarisation-resolved differential phase contrast Open
We present a robust, low-cost single-shot implementation of differential phase microscopy utilising a polarisation-sensitive camera to simultaneously acquire 4 images from which the phase gradients and quantitative phase image can be calcu…
View article: Robust optical autofocus system utilizing neural networks trained for extended range and time-course and automated multiwell plate imaging including single molecule localization microscopy
Robust optical autofocus system utilizing neural networks trained for extended range and time-course and automated multiwell plate imaging including single molecule localization microscopy Open
We present a robust, long-range optical autofocus system for microscopy utilizing machine learning. This can be useful for experiments with long image data acquisition times that may be impacted by defocusing resulting from drift of compon…
View article: Single-cell resolved imaging reveals intra-tumor heterogeneity in glycolysis, transitions between metabolic states, and their regulatory mechanisms
Single-cell resolved imaging reveals intra-tumor heterogeneity in glycolysis, transitions between metabolic states, and their regulatory mechanisms Open
Inter-cellular heterogeneity in metabolic state has been proposed to influence many cancer phenotypes, including responses to targeted therapy. Here, we track the transitions and heritability of metabolic states in single PIK3CA mutant bre…
View article: Multidimensional spectroscopy and imaging of defects in synthetic diamond: excitation-emission-lifetime luminescence measurements with multiexponential fitting and phasor analysis
Multidimensional spectroscopy and imaging of defects in synthetic diamond: excitation-emission-lifetime luminescence measurements with multiexponential fitting and phasor analysis Open
We report the application of phasor analysis and nonlinear iterative fitting to complex spatial and spectroscopic luminescence decay data obtained from multidimensional microscopy of a CVD diamond grown on a HPHT substrate. This spectral a…
View article: FLIM, FRET and high content analysis
FLIM, FRET and high content analysis Open
Fluorescence lifetime imaging (FLIM) provides a means to contrast different molecular species and to map variations in the local fluorophore molecular environment, including to read out Förster resonant energy transfer (FRET), e.g. to assa…