PhD Projects
Funded PhD studentship starting in October 2027
This is an exciting transdisciplinary project between the Department of Physics and the Medical Research Council Laboratory of Medical Sciences. We are looking for a student with a physics, relevant physical sciences or relevant engineering background with a strong interest in optical physics and a strong motivation to apply this to study cancer biology. The project will involve developing and applying state-of-the-art optical imaging technology for high-content analysis of 3D cancer spheroids, including developing image segmentation and processing pipelines using cutting-edge deep-learning-based approaches.
Application deadline: Wednesday 18 November 2026, 09.00.
Please contact christopher.dunsby@imperial.ac.uk鈥痠f you have any questions.
Investigation of the propagation of laser beams with non-Gaussian spatial and phase profiles through turbulent atmospheres and obscuration
The propagation of laser beams through the atmosphere is of keen interest for energy transfer. As a dynamic system, the atmosphere changes on a range of temporal and spatial scales leading to attenuation, spatial beam break up, and scintillation, that can limit the range and efficacy of energy transfer using laser beams. This project will investigate the generation and propagation of a variety of laser beams with differing spatial intensity and phase profiles to understand any benefits over traditional Gaussian profiled beams. One such beam is a Vortex laser beam that carries orbital angular momentum with unique properties and often possess doughnut-shaped spatial intensity profiles. The project will be a combination of experimental and simulation of vortex beam propagation through turbulence (& cloud/fog) and comparison across vortices with different topological charge, Gaussian beams, coherently-coupled beams, and consideration of other possible spatial profiles.
This PhD is part of the . As a student of the Hub, you receive an enhanced stipend of £23,237 per year, plus additional funds of £7,000 a year for travel, conferences and research equipment. This project is co-funded and co-supervised by industry partner .
Eligibility: PhD Candidates must hold a minimum of an upper Second-Class UK Honours degree or international equivalent in a relevant science or engineering discipline. Candidates must be UK Nationals and be willing to apply for and able to obtain Baseline Personnel Security Standard (BPSS) clearance.
For more information please contact Prof Mike Damzen.
Industrial translation of a sub-cellular infrared-laser mass spectrometry imaging platform
This project will develop mid-infrared laser ablation as a sampling method for ambient mass spectrometry imaging (MSI) and integrate the ablation source with commercial high-resolution mass spectrometers. Water naturally present in biological samples strongly absorbs mid-infrared light, so the laser drives desorption without matrix application or other sample preparation. The laser will target spatial resolutions below 5 µm, required for single-cell imaging.
The project is based in the Blackett Laboratory (Department of Physics, 海角社区) and is primarily experimental. The work covers commissioning and developing the mid-infrared laser source, building the microscope hardware and control software, and coupling the ablation source to commercial mass spectrometers (Waters). A central aim is to establish how pulse duration, fluence, wavelength and spot size set material removal, ion yield and spatial resolution. Those parameters will then be built into a robust, user-operable sampling module. The student will also spend time at Waters, the project’s industrial partner, as part of Dr Murray’s four-year Royal Society Industry Fellowship, working on instrument integration and on moving the module from laboratory prototype to commercial platform. The environment spans laser physics, analytical chemistry and instrument engineering.
For more information please contact Dr Robbie Murray.
Light sheet fluorescence microscopy
Light sheet fluorescence microscopy (LSFM) is a high-speed 3D fluorescence imaging method with the advantages of low photodamage to biological samples and low photobleaching of the fluorophores being imaged. However, conventional LSFM requires two microscope objectives placed at 90 degrees to one another to provide orthogonal illumination and detection. Oblique plane microscopy (OPM) is a technique developed in the Photonics Group at Imperiathat uses a single high numerical aperture microscope objective to provide both the illumination light sheet and collection of fluorescence from the sample. In collaboration with the National Heart and Lung Institute, the current OPM system has been applied to image dynamic calcium events in isolated heart muscle cells at video volumetric imaging rates, which gives new insights into dynamic events that may trigger arrhythmias of the heart. It is also being applied in collaboration with the Institute of Cancer Research to achieve 3D imaging in 96 and 384 multi-well plates for higher throughput and time-lapse imaging of arrays of samples. Here, the aim is to study how different genes affect cancer cell morphology and the ability of cancer cells to change their shape over time, which is a factor that affecting metastasis in cancer. More recently, we have developed an optically folded version of OPM that enables two different views of the sample to be obtained that can then be fused together computationally, which we call dual-view OPM (dOPM). This approach improves the spatial resolution and provides a more isotropic point spread function more isotropic. There are three potential topics for PhD projects on OPM:
1) Development of dOPM to study mouse mammary organoid development. This would extend the work of an EPSRC-funded research project joint between Axel Behrens at the Institute of Cancer Research and Guillaume Salbreux at the University of Geneva. This project aims to develop dOPM to allow it to be used to study the growth of up to 50 healthy and cancerous organoids over a period of a week, to develop and apply code to segment – including deep-learning-based approaches – and track every individual cell. The resulting cell fate data will then be compared to physical models of cell and cell membrane behaviour, to study the stochasticity of organoid growth and to look for differences in behaviour between healthy and cancerous organoids.
2) Develop a dOPM system for 3D super-resolution microscopy using single-molecule localisation microscopy (SMLM) approaches. This project will include a detailed assessment of the spatial resolution of the dOPM system, develop improved optical systems to reduce aberrations and then investigate different approaches that correct for spatial variation in the system PSF during the localisation of individual fluorophores. The resulting system will be applied to high-throughput 3D SMLM in arrays of biological samples.
3) Develop a dOPM system optimised for imaging optically cleared fixed tissue specimens. This will involve detailed optical design of the required components, alignment, testing and characterisation. The resulting system will also be applied to study arrays of optically cleared biological samples with collaborators in biology. The cleared specimens will result in larger datasets and the associated challenge of data processing and analysis will require the application and development of automated image segmentation approaches.
For more information see Oblique Plane Microscopy or email Chris Dunsby.
Advanced, low-cost, modular microscopy for histopathology
Conventional histopathology relies on brightfield microscopy of H&E stained histological sections and immunofluorescence microscopy where specific proteins are labelled using antibodies. Where highre spatial resolution is required, e.g. to diagnose kidney disease, electron micrscopy may be utilised. Typically, histopathology entails manual microscopy and visual inspection, although there is an increasing trend to digitise histopthology images and apply image processing techniques, including machine learning for classification. We are working to enhance immunofluoescence by incresing the numbers of different proteins that can be mapped within a single image and by improving the spatial resolution to <50 nm using single molecule localisation microscopy. We are particulary keen to widen access to such advanced techniques and are developing a low-cost modular microscope platform "", implementing bright field and immunofluorescence microscopy with automated slide-scanning. The platform will include super-resolved imaging utilising our low-cost “” technique to image key proteins with clinically validated antibodies. For this, we will complement low-cost instrumentation with practical protocols that will work with existing clinical biopsy samples. As well as being affordable to replicate, this instrument would be straightforward to maintain and would be tested in collaboration with colleagues from lower resources settings. We intend that it could be accessible by clinicians in low and middle-income countries (LMIC). This platform would be generally applicable in histopathology, although this project will focus on developing protocols for diagnosing kidney disease and cancer. As well as developing the hardware, the student would develop and optimise specific protocols for sample preparation and imaging, as well as suitable software tools for data acquisition and analysis, e.g. using MicroManager and ImageJ plug-ins.
The ideal candidate would have a keen interest in the development and application of new biophotonics technologies and would welcome the multidisciplinary nature of the project and the application to lower resourced settings. They would have a first degree in physics or engineering with strong practical skills and competence in programming for image data acquisition and analysis. They would be required to acquire an advanced knowledge of optics and data analysis in the project and to learn sample preparation techniques for histopathology, including immunofluorescnce.
For more information please contact Prof Paul French.
Development and application of new technology for super-resolved microscopy
The recent Nobel prizes for super-resolved microscopy (SRM) underline the revolution tht has occured in optical imaging where the "diffraction limit" has been surpassed to enable features on a scale of 10's nm to be studied in detail, including in live samples. In the Photonics Group we have developed new SRM instrumentation for 3-D stimulated emission depletion (STED) microscopy, for single molecule localisation techniques such as PALM and STORM and for structured illumination microscopy (SIM) combined with fluorescence lifetime imaging (FLIM). We are seeking outstanding multidisciplinary research students who wish to further develop these technologies and apply them to challenges in cell biology, including the study of the cell cycle and the immunological synapse.
For more information please contact Prof Paul French.
Biophotonics technology development for high content analysis of 3-D cell cultures for drug discovery and basic research into disease mechanisms
Increasingly the use of conventional "2-D" cell cultures (typically monolayers of cells on glass or plastic substrates) are being found to be inadequate as models of biological systems for the purposes of fundamental biology research and drug discovery. This project, which would be undertaken in in the Photonics Group in collaboration with colleagues in biology, chemistry and medicine at 海角社区, the Francis Crick Institute, the ICR, the University of Edinburgh and the IRB Barcelona, aims to develop automated assays of cell signalling processes in 3-D cell cultures, particularly tumour spheroids and patient-derived organoids (PDO), where signalling processes are expected to be much closer to the in vivo context than for conventional 2-D cell cultures and therefore could provide more valuable information concerning cell biology and the response to drug candidates and also partially replace the need for animal testing. The project would build on earlier work developing high content analysis (HCA) instrumentation for FLIM FRET assays to read out protein interactions but would address new challenges to improve the imaging performance and analysis of 3D cell cultures in a high throughput (HT) format through the development of new technology. The new 3D HCA instrumentation would specifically be applied to cancer, aiming to better understand and target complexity and heterogeneity in cancer through automated imaging of 3D cancer models including patient derived organoids.
For more information please contact Prof Chris Dunsby and Prof Paul French.
3D polarization imaging for optical storage and quantitative biology
Data centres for cloud computing need to store large quantities of data in an archival format, where durability of the data is paramount. Examples of archive data include medical records, personal backups, insurance data or CCTV recordings. Currently archive data, also called “cold data”, is stored in magnetic tape which is only durable for a few years and data must thus be replicated periodically at huge cost. To address this issue, Microsoft Research is currently investigating the use of 5D high capacity polarisation multiplexed optical data storage in a collaborative research project called . The 5D data storage technique uses a focused femtosecond laser to write data into the bulk of a glass block. At the focus of the laser a small ellipsoidal structure is formed with an orientation and size related to the input polarisation and intensity of the light respectively. Readout and recovery of such polarisation multiplexed data requires development of new advanced polarisation microscopes.
In addition to the field of optical storage, the question of measuring polarisation properties in three dimensions is very useful for biologists. Polarisation imaging modalities offer additional contrast mechanisms, allowing study of tissue birefringence or diattenuation. Collagen fibres, for example, exhibit both birefringence and diattenuation, the magnitude of which provides a measure of the local density and orientational uniformity, which in turn can give insight into the function and bio-mechanics of different structures. Furthermore, polarisation measurements can reveal the micro-structure and composition of tissues. Structural differences in, for example, elastin in skin can result from burns, photodamage or the development of skin cancer. 3D polarisation information can hence play a key role in tissue diagnosis and guided surgery, reducing the need for invasive biopsies or histological studies.
For more information please contact Prof Mark Neil.
Optical projection tomography for 3-D preclinical imaging of disease models
There is currently tremendous excitement associated with new developments in optical imaging and particularly 3-D "mesoscopic" imaging of biological samples in the 100's μm to mm range. Such techniques can permit biological processes to be imaging in situ in live intact organisms, such as drosophila, nematodes and zebrafish. This PhD project concerns optical projection tomography (OPT), which is a mesoscopic imaging technique that is particularly suited for larger samples and has great potential for wide deployment of relatively low cost devices for real-world applications. The PhD research would be undertaken within the Photonics Group laboratories and also in collaboration with colleagues from the Department of Life Sciences and the Faculty of Medicine. The aim is to develop novel approaches to 3-D imaging of biological samples, including zebrafish for preclinical imaging of disease processes, e.g. associated with cancer, inflammation and bacterial infection. In particular, we are interested in developing new computational tools for compressive sensing and enhanced reconstruction of challenging 3-D tomographic data sets. Such tools would enhance our capabilities to study disease mechanisms and test new therapies.
Please more information please contact James McGinty and Paul French.
Receptor recycling and macrophage phagocytosis
This is a joint project supervised by Chris Dunsby and Paul French in the Photonics Group and ouise Donelly and Peter Barnes in the NHLI. The role of macrophages is to clear and remove particles and pathogens and when this fails it may contribute to increased exacerbations and of progression chronic obstructive pulmonary disease (COPD). However, unlike macrophages in other parts of the body, under healthy homeostatic conditions, the lungs are not a serum-rich environment. This is important because most of the mechanisms into understanding the process of macrophage phagocytosis have focused upon opsonic uptake with little known about the mechanisms underlying non-opsonic phagocytosis. Phagocytosis is complex and requires engagement of cell surface receptors and activation of cytoskeletal rearrangements leading to particle engulfment and ultimate destruction inside the phagolysosome. This project will use human monocyte-derived macrophages to investigate the involvement and regulation of specific receptors and cytoskeletal proteins involved in the phagocytosis of different particles such as diesel particulates and pathogens including Haemophilus influenzae and Streptococcus pneumoniae. This will be investigated using flow cytometry and advanced automated fluorescence microscopy techniques in collaboration with the Photonics Group at ImperiaCollege. Receptor trafficking following recognition of bacteria and particles will be examined using real-time microscopy to follow the fate of specific receptors. The role of the cytoskeleton will be investigated by transducing macrophages with lentiviral vectors that will express fluorescently labelled actin and tubulin to allow real time measurement of cytoskeletal rearrangements. To this end, we will use confocal and high content microscopy approaches including the automated optically sectioned (spinning disc) microscopy platform that is available in the Photonics Group providing multi-colour fluorescence intensity and lifetime imaging of fixed and live cells with bespoke image segmentation and quantification capabilities including FRET readouts of protein interactions. We will be able to visualize specific receptor localisation together with cytoskeletal components and will implement 3-channel imaging, using fluorescence lifetime and wavelength to separate labels, and will also explore using FLIM/FRET to read out ROS biosensors (such as HyPer) correlated with bacterial uptake and receptor internalization and use Duolink assays to investigate protein interactions. We will also explore the novel application of super-resolved nanoscopy techniques including SIM and STORM to investigate changes in cytoskeleton and receptor localisation and ultimately identify novel targets for improving macrophage function.
For more information please contact Chris Dunsby and Paul French.
Video-rate volumetric light sheet microscopy for studying the interaction of induced pluripotent stem cell derived cardiomyocytes with mature cardiac tissue
This project will develop and apply novel high-speed light sheet-based 3D microscopy technology developed in the Photonics Group in the Department of Physics. The project will involve modelling, development and modifications to sophisticated optical systems. It will also involve acquiring and handling large (TB) volumes of image data and developing computer algorithms to automatically analyse and quantify biologically relevant parameters.
The biological focus of the project is to understand how induced pluripotent stem cell (iPS) derived cardiomycotes cells interact and integrate with mature cardiac tissue. This is important because iPS derived cardiomycotes are an emerging therapy for the failing heart that have the potential to rejuvenate areas of heart tissue that have been damaged during heart attack. However, the integration of these new cells into the existing tissue and their subsequent function is hard to study using microscopy techniques that acquire images in only two dimensions. Changes in intracellular calcium concentration and trans-membrane voltage will be studied in 3D at video-rate as the wave-front of depolarization induced by electrical pacing spreads across and around the host and grafted tissue. Impulse propagation and induced cell contraction will be recorded in 3D to learn about the interaction of the iPS cells with their mature neighbours. Through these experiments, we will test if action potential duration dispersion and dys-synchrony of Ca2+ release (an index of excitation contraction (EC) coupling) is promoted by stem cell addition.
For further information please see the and , or contact Chris Dunsby.
Accelerating our ability to understand and target complexity and heterogeneity in cancer through automated imaging of 3D cancer models including patient derived organoids
Drug resistance is a major challenge for cancer therapy, arising from heterogeneous cellular behaviours within tumours, where initially identical clonal cells can mutate and adapt to diverse microenvironments. This complexity is rarely addressed in standard assays that typically measure the average response of cell populations in highly artificial contexts and fail to account for outlier cells that may drive drug resistance. There is increasing interest in more complex 3D tissue models, such as patient-derived organoids (PDO) that better recapitulate the complexity of the in vivo context compared to conventional high throughput assays of homogenous 2D cell cultures. However, increasing the physiological complexity of cancer models makes them harder to image – limiting opportunities for high throughput (phenotypic) screening.
In a CRUK-funded Accelerator project, we aim to explore the trade-off between complexity of 3D cancer models and power of assays (in terms of single cell resolution and throughput) by developing and applying modular open source automated instrumentation optimised for 3D imaging of complex cell cultures with a range of optical properties. This automated 3D imaging instrumentation is intended to provide quantitative single cell-resolved readouts of drug-target engagement and responses in fixed and live cell cancer models. We will also explore cell culture and sample preparation (e.g. labelling, mounting, clearing) techniques to enable researchers to optimise 3D assays to address their specific cancer biology questions. Following instrument development at Imperiaand the Crick, we will implement and apply these new capabilities, including with the University of Edinburgh, the ICR and the IRB Barcelona, to 3D cancer biology assays, e.g. to study heterogeneity in the response of cancer cells to chemotherapy - identifying which of the persisting cells are responsible for disease recurrence, to explore the role of the tumour microenvironment for quiescent resistant tumour cell sub-populations and to better understand side-effects of chemotherapy.
For more information please contact Chris Dunsby, Paul French, Erik Sahai or Iain McNeish.
Development of oblique plane microscopy to accelerate our ability to understand and target complexity and heterogeneity in cancer
Developing new cancer therapies requires improved understanding of heterogeneity in cell behaviour. This requires determining single-cell responses, rather than the average responses of cell populations that fail to account for outlier cells that can be responsible for drug resistance. There is also increasing interest in more complex 3D cancer models, such as patient-derived organoids (PDO) that better recapitulate the complexity of the in vivo context compared to conventional high-throughput assays of homogenous 2D cell cultures. However, increasing the physiological complexity of cancer models makes them harder to image using optical microscopy techniques, and this makes screening many samples or conditions in high-throughput screening more challenging.
This PhD project is part of a Cancer Research UK funded Accelerator award between 海角社区, the Francis Crick Institute, the Institute of Cancer Research (ICR), the University of Edinburgh and the Institute for Research in Biomedicine Barcelona. The project will develop, apply and utilise a new state-of-the-art automated light-sheet multiwell-plate oblique plane microscope (OPM) at the ICR to provide 3D imaging of 3D cell cultures and PDOs in 96 and 384-well formats. The PhD student will become expert in the use of the instrument, develop new image analysis pipelines and interpret these results in the context of the biology. The system will be used to provide quantitative single cell-resolved readouts and responses in fixed and live cell cancer models across a wide-range of conditions and provide functionality beyond the commercial state-of-the-art, e.g. providing faster 3D imaging of cell morphology, dynamics and migration in multiwell plate arrays. The project will enable studies of which cells within a heterogeneous cancer population are effectively killed by chemotherapy and which of the persisting cells are responsible for disease recurrence. It will also be used to explore the role of the tumour microenvironment for quiescent chemotherapy-resistant tumour cell sub-populations.
For more information please contact Dr Chris Dunsby or Dr Chris Bakal.