MRes projects available
MRes Bioengineering students work on their research project throughout the year. You can apply for one of the projects listed below, or contact your preferred supervisor to discuss a different project. You must decide on a poential project before making your MRes application to ensure that there is a suitable project available for you.
Applications will be considered in three rounds; to ensure your preferred project is available, we encourage you to apply by the Round 1 deadline of 15th December. If you are applying in a later round, some of the projects listed may have already been allocated so please consider including a second or third choice project in your application.
If none of the projects here is suitable for you, you can contact your preferred supervisor directly to discuss an alternative project. Visit our How do I apply? page for full details of the application process including deadlines.
|Supervisor||Project title||Project type||Project description||Pre-requisite skills/background|
|Rylie Green, Bogachan Tahirbegi||Conducting polymer nanowire and graphene based transistors on paper and PDMS for ultradense ECoG (Electrocorticography) arrays||Lab based||Developing affordable and easy fabrication methods of bioelectronics circuits without the need of clean room facilities are an active field of research. Patterning of the nanocomponents into functional devices is the remaining challenge in the field. In our laboratory, we developed laser based fabrication methods of flexible networks of patterned conducting polymer nanowires for fully polymeric bioelectronics. Shortly, we are developing laser sintering and filter based processing methods for direct pattern transfer of components such as conducting polymer PEDOT nanowires and silver nanowires into paper and PDMS. The resulting films of patterned nanowires are found to possess high conductivity as well as improved wet electrochemical properties in comparison to platinum. Fabricated thin and flexible arrays of PEDOT nanowire films are tested successfully as an Electromyography (EMG) device for muscle contractions. Recently, we discovered that we could fabricate different materials layer by layer using this method. Therefore, we would like to improve our technique and fabricate 3d structures of bioelectronic circuits. MRES student will work as a part of multidisciplinary NISNEM (Non-invasive single neuron electrical monitoring) project to fabricate fully functional transistor based ultradense ECoG (Electrocorticography) arrays for brain research using the methods described above. Once, the device is fabricated and characterized, it will be tested first on neuron cultures and after that on brain.
Prof. Green’s research has been focused on developing bioactive conducting polymers for application to medical electronics. Prof. Green has developed hybrids of conducting polymers and hydrogels to reduce strain mismatch with neural tissue and improve long-term cell interactions at the neural interface.
Dr. Tahirbegi’s research has been focused on the novel electrode materials and new fabrication approaches to enable the fabrication of the super high-density electrode arrays for Electromyography (EMG), electroencephalography (EEG) and micro-electrocorticography (μECoG) to create a disruptive technology to non-invasively detect the activity of large populations of single neurons in the brain and the spinal cord.
|Nano/microfabrication, Electronic circuit design, Characterization of neuron cultures on the ultradense ECoG (Electrocorticography) arrays, Calcium imaging|
|Rylie Green||Living electrode-on-a-chip: development of microphysiological models to study bioelectronic interfaces in vitro||Lab based||The use of metallic electrodes in implantable bioelectronics has been associated with poor tissue integration and the induction of noxious foreign body responses. Biomaterials-based strategies, such as the “Living Electrode” (LE) technology being developed by our lab, could be used to engineer biomimetic interfaces that promote biointegration and enable synaptic neuromodulation of the target tissue. Currently, animal models remain the gold standard to study tissue-level phenomena, since conventional cell culture systems are unable to reproduce the composition, geometry, and spatial organization of bioelectronic interfaces. However, microphysiological “organs-on-chips” are being increasingly used to supplement traditional preclinical models owing to their ability to reproduce the complexity of physiological tissues. This project will focus on the development of microphysiological models that mimic the properties and functionality of bioelectronic interfaces in vitro. A cut and assemble method will be used to fabricate thermoplastic, reconfigurable, and optically clear microphysiological systems for real-time monitoring. Different biomaterials and cell types will be then incorporated into the devices to emulate the multi-layered structure of the LE and the bioelectronic interface in vivo. The student will lead the design, fabrication, and in vitro characterization of LE-on-a-chip devices through the integration of computer-assisted design, microfabrication, biomaterials, and tissue engineering techniques.||Expertise in computer assisted design, laser cutting, photocrosslinkable hydrogels and neural cell culture is ideal, but not required.|
|Rylie Green, Bogachan Tahirbegi||Fabrication of hybrid electrodes and hydrogels from conductive polymer nanowires, graphene and carbon nanotubes on PDMS for non-invasive neuroimaging||Lab based||Current non-invasive neuroimaging techniques, such as electroencephalography (EEG), magnetoencephalography (MEG) or functional magnetic resonance imaging (fMRI), have transformed healthcare over the past decades. Existing metal based electrode technologies used for EEG are not capable of miniaturization due to high noise and low spatial selectivity. The ideal electrode material should be biocompatible and miniaturizable. We will develop novel electrode materials and new fabrication approaches of hybrid soft, flexible and electrically conductive materials (Conducting polymers, graphene and carbon nanotubes) designed to replace the metal electrodes routinely used for non-invasive measurements of neural activity. A range of alternative electrode coating materials have been investigated by Prof Rylie Green and others, including conductive hydrogels (CHs) and conductive elastomers (CEs). These promising approaches use hybrids of conductive polymers (CPs) to provide synergy between low impedance charge transfer and conformability. However, no material technology is available that can address the challenge of fabricating the miniaturized super high-density electrode arrays necessary for the NISNEM (Non-invasive single neuron electrical monitoring) project. In our laboratory, we developed laser based fabrication methods of flexible networks of patterned conducting polymer nanowires for fully polymeric bioelectronics. Shortly, we are developing laser sintering and filter based processing methods for direct pattern transfer of components such as conducting polymer PEDOT nanowires and silver nanowires into paper and PDMS. The resulting films of patterned nanowires are found to possess high conductivity as well as improved wet electrochemical properties in comparison to platinum. Fabricated thin and flexible arrays of PEDOT nanowire films are tested successfully as an EMG device for muscle contractions. MRES student will work as a part of multidisciplinary NISNEM project to fabricate hybrid electrode and hydrogel arrays from conductive polymer nanowires, graphene and carbon nanotubes on PDMS for non-invasive neuroimaging. The fabricated materials will be characterized using microscopy (SEM, TEM, optical) and electrochemical methods. An ultra-dense electrode array will be fabricated from these hybrid conductive materials and will be tested as an EMG device for muscle contractions and as an EEG device for non-invasive neuroimaging.
Prof. Green’s research has been focused on developing bioactive conducting polymers for application to medical electronics. Prof. Green has developed hybrids of conducting polymers and hydrogels to reduce strain mismatch with neural tissue and improve long-term cell interactions at the neural interface.
Dr. Tahirbegi’s research has been focused on the novel electrode materials and new fabrication approaches to enable the fabrication of the super high-density electrode arrays for Electromyography (EMG), electroencephalography (EEG) and micro-electrocorticography (μECoG) to create a disruptive technology to non-invasively detect the activity of large populations of single neurons in the brain and the spinal cord.
|Materials, Nano/microfabrication, electronic circuit design, EEG and EMG recordings on brains and muscles|
|Rylie Green||A bioelectronic implant for cancer treatment||Lab based||This project revolves around aiding in the development of a device for the selective delivery of chemotherapy directly to the site of non-operable brain tumors (glioblastoma multiforme). This device consists of a conductive polymer-based material that can used as an electrically controlled drug delivery system. The goal of this project is to evaluate the drug release profiles for multiple different molecules that are analogs to those commonly used in chemotherapy. Parameters such as molecule size, charge, and stability will be investigated. Characterization of the drug release profiles will be accomplished through chemical, electrochemical, and spectroscopic techniques.|
|Rylie Green||Biofunctionalising electrodes through conductive hydrogel coatings||Lab based||Peripheral nerves cuffs can have there biointegration improved through the use of conductive hydrogel coatings. One of our long-term goals is to improve the long term performance of these electrodes. This projects will investigate reducing inflammation at the site of implantation by the incorporation and release of anti-inflammatory mediators from the hydrogel coatings. Different mediators will be investigated along with different release methods and how these impact the performance of the cuff electrodes.|
|Rylie Green||Injectable brain machine interfaces||Desk based||Deep brain stimulation (DBS) therapy has seen increasing clinical relevance in the last decade. DBS and similar therapeutic techniques require the use of a chronically implanted neural electrodes. This project is focused on the development and characterisation of a minimally invasive, organic, neural electrode system. This electrode system is based on an injectable hydrogel functionalized to facilitate the in-situ electrochemical deposition of conducting polymer directly inside the brain to enable recording and stimulation of neural activity. Initial work will focus on the mechanical, electrochemical and biological characterization of the polymeric electrode system before progressing to investigating in-situ depositions in ex-vivo brain tissue.|
|Rylie Green||Living Bionics: Stimulation to drive neural network development||Lab based||Electrical stimulation has been demonstrated to induce directional neurite growth in various cell types, both human and non-human using biphasic stimulation. This research project aims to evaluate a range of sinusoid stimulation frequencies to drive activity, growth and release of neurotransmitters of developing neurons using a cell stimulation rig made in house.|
|Rylie Green||Living electrodes: Adhering cells through biotinylation||Lab based||Previous work has demonstrated that biotinylation is possible with neural cell types. This project aims to expand this to produce electrodes which can be coated with neural cells to allow for better biointegration at the implant site. The work will involve evaluating different cells types will be evaluated as well as the production of suitable electrode coatings. This builds on our concept of a â€œliving electrodeâ€.|
|Rylie Green||Neonatal EEG Electrode Cap||Lab based||The use of electroencephalogram (EEG) electrode caps in neonatal care presents unique challenges surrounding electrode placement and fixation. This project will develop a neonatal EEG cap using soft, flexible conducting polymer composites called conductive elastomers. The scope of this project covers the design and fabrication of an EEG electrode array cap, development of an interface to monitor 10-20 electrode channels, and validation of biological signals from human subjects.|
|Rylie Green||Printing of flexible polymer bioelectronics||Lab based||The overall goal of this project is to investigate the feasibility of fabricating well defined patterns of conducting polymer-based bioelectronics through printing (inkjet or melt electrospin writing). This technique takes advantage of the viscous liquid phase dispersion of the conductive polymer in solvent to enable printing through a small diameter nozzle. Use of thermal processes will be investigated as methods to control viscosity and printing tolerances. Students with robotics interests will have an opportunity to build a bespoke printer which can be controlled through CAD file geometries and used to create 3D implants from the extruded material.|
|Rylie Green||Spinal cord bridge||Lab based||Nerve regeneration in an injured spinal cord is often restricted. One possible reason may be the lack of topographical signals from the material constructs to provide contact guidance to invading cells or re-growing axons. This research project aims to evaluate randomly oriented or aligned collagen fibers coated on cuff electrodes to study device topographical effects on astrocyte behavior and neurite outgrowth respectively, using electrical regimes.|
|David Labonte||AntGate: a colony door which selects for ant size||Lab based||Many experiments on animals require identification of different individuals—often a difficult task for the human eye. Traditional methods are laborious, involving marking each individual and closely following them over time, necessitating the development of automated methods. The goal of AntGate is to develop a door that opens only for permitted insects, improving the efficiency and reliability of research, while allowing exploration of questions on individual learning and behaviour.Using computer vision models developed in the lab, the mass of an insect will be extracted from a camera located next to the gate, and the gate will be activated if the insect is of appropriate size. The camera will also be able recognize tags, using existing technology , and trigger the gate if the insect is on the permitted list . The core challenge of this project will be engineering a tunnel and gate system seamlessly integrated with the camera input that allows only one insect through at a time. The main insect used to develop this gate will be ants, as their large colony sizes increase the need for automated tools. In this project, you will gain experience in machine learning techniques, camera control, and the building and development of practical tools for research. The system will be used to investigate how size and experience impacts ant locomotion, energetics, and behaviour, contributing to important advances in biomechanics and complex systems. Recommended Literature: Crall, J.D., Gravish, N., Mountcastle, A.M. and Combes, S.A., 2015. BEEtag: a low-cost, image-based tracking system for the study of animal behavior and locomotion. PloS one, 10(9), p.e0136487. Robinson, E.J., Feinerman, O. and Franks, N.R., 2012. Experience, corpulence and decision making in ant foraging. Journal of Experimental Biology, 215(15), pp.2653-2659.|
|David Labonte||Design of an Actively Powered Omni Directional Insect Treadmill||Lab based||Insects are the undisputed champions of legged locomotion, having mastered walking, running, and climbing on virtually any surface, often on steep inclines or even upside down. Therefore, insects have become the inspiration for the design of hexapod robots. To understand which adaptations allow insects to perform these incredible feats, we can use deep learning-based markerless pose estimation to study their locomotion from video recordings. However, this process requires not only intricate camera setups and extensively trained machine learning models but also large numbers of recorded gait cycles, which are both difficult and stressful to obtain - not only for the experimenter but especially the studied animal. In the past, conventional treadmills have been miniaturised and used for these applications, which come with the caveat of requiring the animal to walk a straight line and with external stimulation, potentially provoking flight responses instead of a natural gait. To this end, this project aims to design and build an actively powered omnidirectional insect treadmill that allows for the automated recording of freely walking insects.The goal is for the setup to automatically track the insect walking on the treadmill in real-time and control the motor speeds accordingly so the insect can move in any direction at will while being kept in the centre of the surrounding recording setup. As we aim to investigate the locomotion of a broad range of species walking on different substrates, the belts of the treadmill will need to be interchangeable to enable the use of various materials.As the project encompasses designing and building an omnidirectional treadmill as well as implementing its control loop, experience in Computer-Aided Design, rapid prototyping, and programming are required.For some design inspiration / suggested literature of large omnidirectional treadmillsPyo, S., Lee, H. and Yoon, J. (2021) ‘Development of a Novel Omnidirectional Treadmill-Based Locomotion Interface Device with Running Capability’, Applied Sciences, 11(9), p. 4223. doi: 10.3390/app11094223.Souman, J. L., Giordano, P. R., Schwaiger, M., Frissen, I., Thümmel, T., Ulbrich, H., De Luca, A., Bülthoff, H. H. and Ernst, M. O. (2011) ‘CyberWalk: Enabling unconstrained omnidirectional walking through virtual environments’, ACM Transactions on Applied Perception, 8(4). doi: 10.1145/2043603.2043607.|
|David Labonte||Development of a muscle-fibre tracking algorithm||Lab based||µCT-data of muscular tissue are almost ubiquitous, but their utility for quantitative research is limited, as automated analysis of key parameters such as muscle fibre length, radius, and pennation angle is only available in expensive commercial software, or needs to be done by hand. In this project, we aim to address this problem by developing an algorithm which enables automated tracking of muscle fibres, so extracting key parameters from segmented ÂµCT scans of insect heads.Some basic knowledge in python is required for this project.|
|David Labonte||FrankenInsects: Building an open-source and portable device for targeted insect muscle stimulation||Lab based||Many arthropods have evolved the ability to lose their limbs as a defensive strategy against predators. For example, it is thought that stick insects use a specialised muscle to facilitate autotomy of their leg. In this project, you will build a device that can stimulate insect muscles in vivo to investigate the role of certain muscles in leg autotomy. This will electrical stimulation of a specific region of the insect leg, as well as synchronised video-recordings to visualise the outcome of the stimulus. The design of the final device will be open-source for the benefit of other researchers. A background in electronics is required, and an appreciation for animal physiology is desirable.|
|David Labonte||Going out on a limb: How do insects actively lose their limbs||Lab based||Many arthropods have evolved the ability to lose their limbs as a defensive strategy against predators. Although this strategy – called autotomy – has been extensively studied in reptiles, relatively little is known about the underlying mechanisms for autotomy in insects. In this project, you will be responsible for building a set-up to record this process in 3D and to analyse the kinematics of autotomy using several different species of insects. More specifically, you will adapt an existing design that can accommodate multiple cameras to capture the movements of the insect as it autotomises, and then use DeepLabCut to reconstruct these movements in 3D for analysis. A background in robotics or electronics is required, and an introductory-level understanding of machine learning is desirable.|
|David Labonte||Markerless pose estimation to study the locomotion of load-carrying leaf cutter ants||Lab based||Imagine, instead of driving your car to the nearest supermarket, you would have to carry your cars weight in groceries over your head while doing parkour during rush hour in the middle of a crowded city for twelve hours every day What sounds insane to a human is the daily life of a leaf-cutter ant. It is widely known that ants are capable of carrying loads greater than twenty times of their own body weight when transporting food back to their colony. As they live in symbiosis with a fungus they grow, the colonies survival and growth depend on the workers ability to harvest substantial amounts of plant material to feed the fungus. What enables these tiny creatures to move freely under the weight of the cut leaf fragments? How does the additional load on their joints influence their locomotion?These questions are to be investigated in this project. Instead of relying on manual evaluation of video data, you will train a deep neural network architecture based on DeepLabCut to perform pose estimation of ants, carrying different loads. This approach enables us to automate the extraction of tracking data when comparing the influence of load on workers of different sizes and potentially different species. You will also be involved in the design of a multi-camera setup to record individual workers from various angles synchronously, in order to create 3D reconstructions of the recorded gait cycles.Due to the proposed methodology, prior experience in machine learning and computer vision, as well as mechanics are required for this project. You will gain insights into the use and implementation of deep neural networks, creation and challenges of labelled training data sets, 3D reconstruction of tracking data, and the biomechanics of insect locomotion.For more info on the group: http://evo-biomech.ic.ac.ukRecommended Literature:1. Mathis, A. et al. DeepLabCut: markerless pose estimation of user-defined body parts with deep learning. Nat. Neurosci. 21, 12811289 (2018).2. Zollikofer, C. P. E. Stepping patterns in ants. J. exp. Biol. 127, 119127 (1994).3. Wilson, E. O. Caste and division of labor in leaf-cutter ants I. Overall Pattern in A. sexdens. Behav. Ecol. Sociobiol. 7, 143156 (1980).4. Moll, K., Roces, F. & Federle, W. How Load-Carrying Ants Avoid Falling Over: Mechanical Stability during Foraging in Atta vollenweideri Grass-Cutting Ants. PLoS One 8, e52816 (2013).|
|David Labonte||Markerless pose-estimation to study the effects of leg loss on insect locomotion||Lab based||Insects regularly lose or let go of limbs, yet are still able to walk. The strategies insects use to adjust locomotion after leg loss may inspire strategies to enable robots to continue to function even when limbs are lost or damaged. In order to understand more about the adaptations deployed by insects upon leg loss, we will use deep neural network based markerless pose estimation to study insect locomotion. Our goal is to not only gather a deeper understanding of hexapod locomotion with different numbers of legs, but also to produce a versatile, robust and automated detection and tracking process for studying limb orientations in diverse climbing animals.A background in machine learning and computer vision is required for this project, as one of our main objectives is to train and evaluate an architecture based on DeepLabCut, in order to accurately estimate the limb positions of different species and investigate the transferability of the learned models. You will gain insights into the use and implementation of deep neural networks, creation and challenges of labelled training data sets, 3D reconstruction of tracking data, and the biomechanics of insect locomotion.For more information on the group: http://evo-biomech.ic.ac.uk/|
|David Labonte||The metabolic costs of insect herbivory||Lab based||Leafcutter ants are the principal insect pests in the Neotropics, harvesting up to 4500m² of plant matter per year. Using their sharp mandibles, they cut a variety of food sources such as leaves, fruit and flower petals. Herbivory at such a large scale requires a large amount of cutting, which in turn uses a lot of energy. The energetic cost of such an endeavour can vary based on both the size of the ant and the toughness of the plant. Here we will look at how material properties influence the amount of energy needed to cut by ants of one size. Our goal is to gain a deeper understanding of how energetic costs scale with material properties.In this project, you will investigate this question with a multi-disciplinary experimental approach. An artificial leaf system of repeatable and controllable material properties will be made out of polymers. Using an ultra-sensitive flow-through respirometry system, we will measure both resting metabolic rates, and active metabolic rates during cutting synthetic leaves. For more information on the group visit:http://evo-biomech.ic.ac.uk/|
|Rodrigo Ledesma||Deciphering the codon usage code and its role in metabolism with applications in synthetic biology||Lab based||The DNA codes for all the heritable information required to form life. Due to the degeneration of the genetic code, different DNAs can code for the same proteins, this is possible because several codons (groups of 3 nucleotides) can be translated into the same amino acid. This property emerges in all living systems and there are many theories that justify this mechanism. One of these theories, yet to be explored, is that the codons represent an additional level of regulation. This project will explore variations in codon usages in specific metabolic pathways or conditions in order to identify novel regulatory elements. This project could lead to important biological insights that can be used to understand diseasese and to improve synthetic biology approaches.|
|Rodrigo Ledesma||Synthetic biology and metabolic engineering for microbial biotechnology and bioengineering||Lab based||Microorganisms are important for both industrial bioprocesses and biomedicine (i.e. gut or skin microbiota). The lab is interesting in a wide array of organisms, from yeast (S. cerevisiea and Y. lipolytica), fungus (A. gossypii) and bacteria (E. coli and Acetobacter) to complex microbial consortia (human and industrial microbiota).The manipulation and optimization of microbial metabolic pathways are the keys to biotechnology and a bio-based economy. we are highly interested in hacking metabolism using synthetic biology tools to create new properties and enhanced behaviors in microbial cells. The engineering strategies are not only designed to produce new high-value products or higher amount of pre-existing products but also to facilitate the downstream and upstream parts of the bioprocesses.|
|Jimmy Moore||Lymph Node Implant for Breast Cancer-Related Lymphoedema||Lab based||A large percentage of breast cancer patients who undergo lymph node resection develop an incurable swelling of the arm called lymphoedema. We are developing an implant to replace the fluid delivery characteristics of lymph nodes. We have developed a lymph node implant that releases a growth factor to regenerate the damaged lymphatic vessels. We would like to visualize the release and flow of the growth factor once it is implanted in the tissue. We can do this using a microfluidic chip that simulates fluid flow like in tissue. The goal of this project is to use a fluorescence microscope to live image the microfluidic device as the fluorescent-labelled growth factor flows through it over time. This will help us understand where the growth factor travels to within the surgical site.|
|Jimmy Moore||Drug mass transport in the interstitium||Desk based||When drugs are injected into interstitial spaces (e.g., intramuscularly), they may be taken up by either blood or lymphatic vessels. For some drugs, uptake into one or the other may be desirable to enhance their mechanisms of action. The direction of uptake depends on parameters such as the size of the drug (and delivery vehicles, if present), electrostatic charge, and local tissue conditions. While there is experimental evidence of the effects of some of these parameters, the underlying forces have not been analysed in a sufficiently quantitative manner. Better understanding of these forces would enhance therapeutic design and delivery. A theoretical model of drug transport through interstitial spaces will be constructed, with the possibility of performing some targeted in vitro experiments.||Maths, physics, biology|
|Jimmy Moore||MRI phantom to enable imaging of lymphatic vessels||Lab based||Lymphatic vessels are notoriously difficult to image. They are mostly <1mm in diameter, and lymph moves at small velocities on the order of mm/sec. Furthermore, the vessels contract strongly as part of their pumping function and thus empty out most of any contrast medium within. We are collaborating with MRI physicists who aim to develop novel imaging protocols targeting lymphatic vessels. This process would be greatly facilitated by an in vitro flow phantom that imitates in vivo lymphatic movement and flow. The project would involve constructing such a phantom using some combination of 3D printing, polymer casting, and pumping actuation. To be usable with MRI, there must be no metal components. This presents an interesting design challenge with potential to help revolutionise clinical capabilities to image a medically important system.||Mechanics, DIY|
|Supervisor||Project title||Project type||Project description||Pre-requisite skills/background|
|Christopher Rowlands||A New Head Mounted Display Concept: Virtual Reality in a Pair of Sunglasses||Lab based||In order to experience immersive virtual reality, a display must have a large field of view and a high resolution, otherwise the user will feel like they are 'looking at the world through a toilet roll'. Commercially available head-mounted displays like the Occulus Rift, HTC Vive and Playstation VR solve this problem by placing the screen in front of the eyes, but this is clearly an inelegant solution as it involves basically strapping a brick to your face. More recent designs such as the Microsoft Hololens and Magic Leap One use holographic gratings to project light into the eye, but these have a smaller field of view, leading to the 'toilet roll' problem described above.The Rowlands lab is currently developing a new type of holographic display, which can achieve a large field of view along with high resolution, by making the hologram itself active, rather than passive. Instead of projecting the whole image at once, the display scans a beam across the eye at high speeds, producing the illusion of high resolution but without the compromises needed for the Hololens or Magic Leap One.The student on this project will conduct theoretical and experimental studies into the feasibility of this design. They will be using finite-difference time-domain modelling and fabricating electro-optically active waveguides in an attempt to demonstrate a proof of principle, with the goal of producing a device that can project simple patterns into a stationary eye. The ideal student will have a good background in computer modelling, an interest in microfabrication and photolithography, and possibly some electrical engineering expertise. Any necessary skills can be taught however.|
|Christopher Rowlands||Advanced Microscopy for Everyone||Lab based||One of the workhorse instruments in a microscopy suite is the confocal microscope. Unlike a normal microscope, it can image objects in three dimensions, which helps explain why modern laboratories use theirs so extensively, in fields as diverse as histopathology, neuroscience and cell biology. Nevertheless, confocal microscopes are very expensive, costing hundreds of thousands of pounds in many cases, despite containing no particularly expensive parts. This enormous price puts the instrument out of reach of researchers in the developing world, and even several laboratories in developed countries as well. This project will seek to redress this balance, by developing a confocal microscope using modern low-cost rapid prototyping facilities, off-the-shelf microcontrollers and careful design, broadening access to this core technology throughout the world.The student on this project will be responsible for building this instrument, based on a modern design known as a 'rescanned confocal'. This will require some work with a CAD package (like Solidworks), some 3D printing or CNC machining (possibly outsourced) and a bit of programming experience. Students should not be put off taking this project if they don't feel they possess these skills though, as they can be taught. Motivation and a willingness to learn is much more important.|
|Christopher Rowlands||Analyzing hyperspectral oncological images using cutting-edge data processing||Lab based||Deep learning techniques have found considerable use in pattern recognition for image analysis, but in medical imaging there are often additional data dimensions which can be exploited for improved diagnosis. This project will involve one such dataset - hyperspectral Raman images taken from tumour resection margins. In this case, the goal is to identify whether any tumor remains in the image, and if so, where it is located. Neural networks and other deep learning techniques will be used to perform this analysis, incorporating spatial and spectral information to make an accurate diagnosis.|
|Christopher Rowlands||AstroTIRF: Pinning light to a surface||Lab based||Total Internal Reflection Fluorescence Microscopy is an imaging technique that can take pictures of cells with incredible resolution - it is able to see things that are the thickness of a virus. While this is very important for imaging of complex cell processes, the limitation is that we can only see the surface of the cell - we can't see inside, as we can with a normal microscope. Nevertheless, it might be possible to interfere two illumination patterns together and combine the high resolution of TIRF with the ability to see features hidden inside the cell. The student on this project will be responsible for delivering on this vision.The student will start this project by modelling the system using optical wave propagation software, before moving on to optics experiments in the lab. Initially work will be on a test system, but eventually will be incorporated into a microscope and used to image cells. The ideal student for this project would have a good background in programming, and some experience with building precise mechanical devices, but the student could be taught anything they need to know.|
|Christopher Rowlands||Building a next-generation scanning microscope||Lab based||Scanning optical microscopy is a workhorse tool for modern biology - it can see things deeper into tissue, with 3D resolution, and observe fast dynamic events. Recently, Drs Rowlands and Pantazis have been interested in developing a technology called Primed Conversion (https://www.nature.com/articles/nmeth.3405) in order to make it easier to use for researchers around the world. Primed conversion involves optically tagging cells as they develop, allowing us to trace the development of an organism from a single cell all the way up to a complete animal and seeing which cells are destined to form which parts.The missing piece for the widespread use of Primed Conversion is the integration of the system into microscope systems. The student on this project will build an add-on to a microscope which can perform Primed Conversion, aligning two lasers and scanning them in parallel through the sample. The skills required involve programming, electronic engineering, some mechanical design and some optical engineering, but any skills that the student doesn't possess can be taught. The most important thing is an aptitude for learning quickly and hard work.|
|Christopher Rowlands||Detecting bioweapons with stand-off Raman spectroscopy||Lab based||Bacillus anthracis, commonly known as anthrax, is a potent bioweapon. Having first been used in World War Two, there have been a number of attacks and close calls, ranging from a 1979 accidental release of spores in the former Soviet Union which killed 69 people, several attempts at terrorist attacks by the Aum Shinrikyo cult in Japan in the 1990s, and the 2001 anthrax letter attacks on senators in the United States.Anthrax is a powerful bioweapon not only due to its pathogenicity, but because it can form spores which are extremely difficult to eradicate. These spores are stable for decades, and are resistant to radiation, ultraviolet light, dessication, extreme heat and cold, as well as a number of chemical disinfectants. Identification and detection of these spores is critical to decontamination of an area after a suspected attack, but for obvious reasons, it is not a good idea for a user to get too close to a suspected contamination. Finding a way to detect these spores at ranges of 10m and above would be extremely beneficial for first-responders who wouldn't have to risk their lives to test a suspected release site.One way to perform this detection is using Raman microscopy. The student on this project will be responsible for building a system to perform Raman detection at long distances, without compromising on sensitivity. This system will be able to detect Bacillus subtilis (a benign analog of anthrax) without the need for the user to come near the sample location, and the project will involve some optical engineering, programming, and potentially some electrical engineering.|
|Christopher Rowlands||Developing algorithms to sculpt light in 3D||Lab based||Photolithography (literally 'light stone-writing') is widely used in the semiconductor industry for patterning microchips, but using light to trigger a chemical or physical change has many uses in biology as well. 3D bioprinting, photodynamic therapy, image recording, and optogenetic control of neurons all employ light to induce a change in a biological system. One important limitation of conventional projection-based optics is that the change is induced by a single photon. This has a subtle problem in 3D applications, because if one wishes to confine the photo-response to a particular plane, the regions above and below the plane are also illuminated.This is a particular problem in optogenetics, a cutting-edge technique in which light is used to excite neurons in the brain. Here, it is desirable to excite one neuron but not the ones above or below, yet this is impossible with conventional optical projection. Fortunately, there is a potential solution - one can use high-speed projectors to make holograms that change very rapidly. None of the projected images are intense enough to trigger a neuron on their own, but the sum of many of them is. One can therefore find a series of patterns that trigger the desired cell, but cause the light above and below the desired cell to 'miss' the important regions, thus having no effect.The student for this project will work on developing an algorithm that can, for a given distribution of neurons, find a sequence of holograms that trigger a single cell but don't affect the surrounding cells. They will develop software to control a projector in order to make these patterns, and if everything goes according to plan, it may be possible to test the algorithms in a laboratory setting.The student for this project should have a moderate to strong mathematical background, and some experience in Matlab or another similar programming environment. If necessary they should have, or be able to develop the lab skills necessary to test their software in real life.|
|Christopher Rowlands||Diagnosing Disease with Speedy-Scanning Raman Readout||Lab based||Ordinary microscopes can use light to diagnose diseases but they do so using a limited number of colours. If we replace the three colours of the spectrum with thousands of wavelengths in a spectrum, we can learn much more about each pixel in an image. This is the promise of Raman microscopy.Raman microscopy uses highly intense laser light to illuminate a sample. When the laser scatters from the sample, a very small fraction of it changes in wavelength, and this change is unique to a particular chemical bond. By mapping the sample using a spectrometer (which can image and quantify these wavelength changes) we can therefore gain chemical information about the sample, which is sufficient to diagnose a number of diseases, including (most notably) cancer.The downside of Raman microscopy is that it is slow, and while it can be sped up by increasing the illumination intensity, eventually this comes at the cost of damaging the sample. The key to increasing imaging speed is therefore to share the laser out over more pixels, recording from them in parallel. The student on this project will develop a new system that can illuminate dozens of points simultaneously, thus significantly speeding up the imaging process. This will involve working on an existing Raman microscope, modifying it to implement this new scanning process. The work will then progress to methods for rapidly diagnosing cancer using tissue biopsies.The ideal student on this project would have a reasonable background in programming, but all other skills and techniques can be taught.|
|Christopher Rowlands||Drugs on Demand - towards an automated synthesis platform||Lab based||Modern drug synthesis occurs in large chemical plants, or at the very least on a lab bench, and requires extremely well-trained researchers, lots of glassware or plant components, and great expense. This project tries to do away with all of those limitations, allowing essentially any synthesis to be performed on a reconfigurable microfluidic chip. Microfluidics has great promise, particularly for small-scale syntheses, in that it can perform reactions more rapidly, under more tightly controlled and uniform conditions, and in an entirely automated manner. Unfortunately, chip designs for one reaction cannot be easily modified or used for another reaction, which limits flexibility. This new microfluidic chip will be able to emulate any other design, changing reaction conditions and configuration rapidly and easily, ushering in a new era of microfluidic drug synthesis.The student on this project will be working with a postdoc to develop the new microfluidic chip. It uses tiny an array of tiny wax motor valves, so first the student will be responsible for designing and characterizing these valves, before scaling up to larger arrays. The ideal student will have some experience in CAD modelling, design of simple electrical circuits, and basic programming, but these are by no means essential - all candidates will be considered, and any required skills can be taught.|
|Christopher Rowlands||Dynamic Dichroic Mirrors - making reprogrammable optical filters for stand-off chemical imaging||Lab based||Hyperspectral imaging is used in applications from chemical weapon detection to cancer diagnosis, from fraud monitoring to industrial quality control. Currently wide-field camera-based hyperspectral imaging systems are based around single filters - you must know exactly what you're looking for in order to select the right filter. The Rowlands Lab is working on a new type of optical filter which can be reprogrammed at will, allowing arbitrary chemicals to be searched for, for example.Currently, the optical components have been assembled, but need to be tested and new materials tried out. The student on this project will be responsible for taking this system from prototype stage to working tool, and will have to develop a number of skills, from instrument development and debugging, to materials development and optimization and finally development of robust testing methods. There is also the potential for publication or intellectual property development, should groundbreaking advances be made.The ideal student on this project would have a willingness to learn, adaptability and some background in the physical sciences, engineering or computer science. That said, talented students from any background will be considered, and the relevant knowledge taught.|
|Christopher Rowlands||High-precision LEGO photonics||Lab based||Optical instruments require the most precise modern precision machining techniques - even a basic biomedical microscope contains components aligned to sub-micron accuracy. This precision alignment comes at a cost, and commercial microscopes can easily cost hundreds of thousands of pounds. To try to reduce this cost, we can turn to one of the planet's foremost experts in low-cost high-precision engineering - the LEGO Group.LEGO is a miracle of modern engineering - each brick is moulded to a tolerance of 20 microns, smaller than the diameter of a white blood cell. By designing optical systems that can accommodate slightly degraded tolerances we can dramatically broaden the ability of researchers worldwide to construct custom optical systems without the need for expensive machined parts and precision alignment methods. The student on this project will be constructing high-precision optical systems for biological applications based on low-cost LEGO parts. These might include beam expanders, automated stages, power controllers, adjustable mirrors, and even full microscopes (complete with automated stages, cameras, autofocus and a variety of illumination sources).The ideal student for this project will be innovative and creative, quick to learn and willing to work hard. Some programming skill may be helpful, but a problem-solving mindset and curiosity are more important. All necessary practical skills (especially traditional optical alignment) can be taught.|
|Christopher Rowlands||Making a true 3D camera||Lab based||When it comes to microscopes, there are no shortage of approaches to imaging a 3D sample: multiphoton microscopy, light-sheet microscopy, confocal and so on. What is notable about these techniques however is that they work by imaging a volume one plane at a time, and thus aren't really imaging in 'true' 3D. This project will change all that, as the student will be working on a system that can really image a volume (animal heart, brain, cancer organoid, tissue sample etc.) in 3D.The system itself is based on a design called a Framing Camera. This uses a mirror to reflect light to a number of cameras, each of which can see a different plane in the sample. The student in this project will be constructing the prototype of this system, which will involve assembling the cameras and the optical system, programming the mirrors, and ultimately building the world's first true 3D microscope.The ideal student for this project will have a good background in mechanical, electronic or software engineering, and a keen interest in picking up new skills. He or she will be ambitious and self-motivated, and a quick learner. There is no specific requirement on skills as these can all be taught.|
|Christopher Rowlands||Next-Generation Drug Synthesis: Optimizing bioreactors with lasers||Lab based||A great many modern drugs are manufactured, not in chemical reactors, but in bioreactors: steel or glass vessels housing many litres of cell culture medium and a colony of genetically-modified cells which produce the drug itself. As this mass-manufacturing technology underpins the production of pharmaceuticals worldwide, there is considerable interest in achieving even modest gains in efficiency and yield which, when scaled out over a large-scale manufacturing process, contribute to dramatic cost-savings. Unfortunately, if optimising a chemical reactor is hard (with all the inhomogeneities in temperature, pressure, reagent concentration and so on), optimising a bioreactor is much harder still, because cells are much more sensitive to their local environment. Fortunately, researchers in the Polizzi lab in Chem Eng, and the Rowlands Lab in Bioeng are working on a way to monitor these cells in situ, using optical imaging and fluorescent reporter cells.The student will work on a system to image the fluorescence from a variety of locations within a large (liter-scale) volume using a large number of optical fibers coupled to a microscope. The student will use the system to monitor reactions in the reactor, and try to reconstruct the resulting fluorescence distribution. The student will need some basic precision manufacturing skills and an ability to prototype ideas quickly, but the most important is a willingness and ability to learn quickly.|
|Christopher Rowlands||Speedy Spectroscopy - investigating new ways to speed up vibrational spectroscopy||Lab based||Raman spectroscopy is an analytical technique which provides a wealth of information about a sample, allowing identification of molecules and even diagnosis of diseases (especially cancer). It requires no labelling of the sample, is extremely specific, and applicable to almost any compound imaginable. Given these virtues, it is fair to ask why it is not more ubiquitous in medical diagnosis, and the answer is that it is painfully slow. Spontaneous Raman microscopy takes around a second to collect even a low-quality spectrum, and this is simply too slow as a tool for mapping tissue, or screening cells. Finding a way to speed the process up would be ideal.In this project you will be exploring techniques to speed up Raman microscopy, for example by using parallel excitation, light-sheet imaging, electron-multiplying CCDs, high-power lasers or high-performance signal-processing methods. Some useful skills might include programming hardware devices / signal processing algorithms, optical alignment or precision machining, but these are not required, and the requisite skills can be taught.|
|Christopher Rowlands||Towards a Raman-Activated Cell Sorting system for cancer screening||Lab based||Nobody needs to be told how much of a threat cancer poses to the population; even worse, certain types of cancer (such as pancreatic cancer, or certain types of ovarian cancer) are so difficult to detect that once they are observable, the prognosis is very poor. A screening method that can detect the limited number of cancer cells circulating in the blood would be of interest in these cases.Fluorescence Activated Cell Sorting, or FACS, is a routinely-used method for sorting cells into different categories based on fluorescence. Unfortunately, cancer cells aren't fluorescent, and finding a good label is arduous and often ineffective. The alternative is to use some form of intrinsic contrast, such as the Raman effect. The Raman effect allows molecules to be identified by the characteristic vibrational frequencies of the bonds in the molecule itself, thus it is very specific and requires no labelling or staining. The goal of this project is to take the first steps towards a combined Raman-Activated Cell Sorting (RACS) and single-cell sequencing instrument that can identify rare circulating tumour cells early.The student on this project will first be responsible for designing, building and programming a Raman microspectrometer, and then using it to analyse different cell populations (some made up of known cancer cells, some not) to see whether the system can distinguish an individual cancer cell from the thousands of other cells also found in the blood. The ideal student will have a background in programming, some CAD skills, and experience building instrumentation, but these are by no means a requirement; the student will be taught anything necessary that they do not already know.|
|Christopher Rowlands||Virtually Microscopic - building a virtual-reality interface to complex microscopic data||Lab based||The design of a microscope has remained the same for 350 years: the user looks down an eyepiece, moves a stage and focuses the lens to see features of interest in a sample. Nevertheless, the recent availability of low-cost virtual reality systems means that users need no longer be tethered to the instrument; researchers, doctors and students alike can explore the rich datasets that are gathered by modern microscopy, or even guide the microscope in real time, gaining a new perspective which hopefully leads to new insight.As a researcher on this project, you will have good programming skills and some familiarity with complex Software Development Kits (SDKs). You will be programming a head-mounted display to project part of a large microscopic dataset, updating the display as the user moves around the environment. As the project progresses, you will be incorporating control over the microscope as well, rapidly capturing data to allow the user to explore a sample with as much freedom as possible.|
|Christopher Rowlands||Watching Sound - creating a new technique for stand-off ultrasound imaging||Lab based||Ultrasound is one of the safest, cheapest and most powerful ways to image deep within the body. Compared to MRI it is fast, easy to use and significantly less onerous on the patient. Nevertheless, there are limitations which we are working to overcome.All current forms of ultrasound imaging require the user to place an ultrasound probe in contact with the skin. This in turn requires a skilled ultrasound technician to apply ultrasound gel and move the probe to image the organ of interest. A more elegant solution would be to use optical imaging to see the acoustic signal (as well as exciting it), thus removing the need for the technician, gel or even for the patient to lie on a bed. The acoustic signal could be simply recorded by imaging the patient's body with a very fast camera.The Rowlands lab is working on developing optical ultrasound detectors based on evanescent wave sensors; these are extremely sensitive to minute changes in the position of an array of nanoparticles, and thus to a passing acoustic wave. The student working on this project will help develop this new type of ultrasound detector, building the nanoparticle suspension, excitation optics and imaging / readout. The ideal student would have a background in the physical sciences or engineering, with a willingness to try new things and learn. The Rowlands lab is highly multidisciplinary, with lots of different researchers studying lots of different things, so new perspectives and approaches are encouraged. The student can be taught most (if not all) of the skills and techniques they will need to know.|
|Christopher Rowlands||World's Fastest Video Camera||Lab based||High-speed imaging requires specialized cameras to capture fleeting events like explosions, hypersonic flow, or even the passage of light. In this project, we are interested in the oscillations of an ultrasound bubble, which occurs at frequencies of a few megahertz. As such, we will need to build a camera that can image at around one hundred million frames per second, for a duration of around one second. These requirements are far beyond even the fastest cameras available today, necessitating a new development program.The student on this project will be building part of the camera, specifically a small piece of the sensor. Using newly-available silicon photomultiplier arrays, we will be constructing a small-scale prototype with the sensitivity and speed necessary to capture data at these incredible speeds. The ideal candidate will have a good background in electrical engineering, and will be designing and testing readout circuitry for the camera. Once this is complete, they will begin testing a small-scale prototype by building the large-scale optical system required to magnify the bubbles enough to be seen by the sensor. This project will also involve a certain amount of programming, in order to reconstruct the data after the experiment is complete.|
|Simon Schultz||Mapping amyloid plaques in whole brains using serial section two photon tomography||Lab based||Alzheimer’s Disease (AD) is the most common type of dementia – accounting for about 70% of the nearly 50 million dementia cases in the world. It is characterised by neuronal degeneration caused by the presence of extracellular amyloid plaques and neurofibrillary tangles in the brain. Genetically modified rodent models have helped advance our understanding of the underlying mechanisms of this disease. One of these models, called 5xFAD, recapitulates many AD-related phenotypes and has a relatively early and aggressive presentation. Amyloid plaques are seen in mice as young as two months of age. However, the degree to which the amyloid plaques affect behavioural performance in these models is still not well known. In this study, high throughput serial two-photon whole brain imaging will be performed in order to map the spatial distribution of amyloid plaques across age in 5xFAD mice, labelled with Methoxy-X04, using the TissueCyte imaging platform. Together with the region-specific progression of plaque densities in critically affected brain structures, these models present an invaluable tool for early intervention and improved pre-clinical assessment of potential therapeutic approaches for AD. This project will involve wet lab work as well as development of python or MATLAB based image analysis code.|
|Barry Seemungal (Brain Sciences), Simon Schultz||Assessing the effect of Dopamine on mutual information of Perceptuo-Motor Coupling in humans via transcranial magnetic stimulation||Lab based||The human brain is an information processing machine. Our brain can accurately decode external and internal events, like when our finger moves, this could be from our voluntary command or passively from an external force. Transcranial magnetic stimulation (TMS) to the human motor cortex causes an involuntary hand muscle contraction which uncouples muscular contraction from volitional control. If we apply low intensity TMS then we can objectively measure muscular contraction (via Myogenic Evoked Potentials) sometimes without conscious awareness of the contraction. This setup allows us to assess the efficiency of sensory processing by measuring the mutual information between MEP responses and perceived contraction (contraction versus no contraction). Mutual information is the difference between two entropies, a “noise + signal” and a “noise” entropy, and enables an optimal measure of changes in cortical sensory processing. We will assess how a Dopamine agonist modulates sensory processing measured by changes in mutual information. Dopamine is an important neurotransmitter and its loss mediates several features of Parkinson’s Disease (PD). We hypothesise that dopaminergic activation enhances the mutual information of perceiving a TMS-evoked MEPs in healthy subjects. Future studies will involve PD patients. See here for output from a similar Masters project: https://www.jneurosci.org/content/36/36/9303||Programming and data analytical skills. Students will receive training specific to the laboratory setup.|
|Claire Stanley||Development of microfluidic technologies for biological research||Lab based||Our research focusses on developing microfluidic or "Organ-on-a-Chip" technologies to probe the interplay between soil-dwelling organisms at the single cell level. This technique has a great potential to provide a unique view of biological events at the level of single organisms and cells by enabling precise environmental control, high-resolution dynamic imaging, the simulation of environmental complexity and affording quantitative information. We are involved in projects positioned at the interface between bioengineering, microbiology and plant biology, including the study of bacterial-fungal interactions at the single cell level, the defence response of fungi upon predation by nematodes and the adaptation of plant roots towards environmental asymmetry. Please contact Dr Claire Stanley (firstname.lastname@example.org) to find out more about available projects. More information about our research can be found at www.claire-stanley.com|
|Molly Stevens||Developing innovative biomaterials for regenerative medicine, advanced therapeutics and biosensing||Lab based||We have a range of projects available focused on the design of novel material-based strategies applied to disease diagnostics, regenerative medicine, advanced therapeutics and drug delivery. Our portfolio includes fascinating research from understanding the fundamental mechanisms of the cell-material interactions to developing highly translatable technologies such as ultrasensitive point-of-care diagnostics, bioinspired tissue engineering scaffolds and pioneering bionanomaterial characterisation equipment. Our research group provides a welcoming, inclusive and stimulating environment to develop creative and collaborative early career researchers. We are an award-winning, highly multidisciplinary team looking for the very best students in chemistry, engineering, cell biology, physics, materials science and medicine. Diversity in all its forms is important to us, and we welcome students from all over the world. Please contact Akemi Nogiwa (email@example.com) for more information. www.stevensgroup.org.|
|Majid Taghavi||Soft-rigid hybrid robotic material||Lab based||Soft robotics built from highly compliant materials suggests safe and adaptable technologies for many applications including human-machine interactions (e.g. surgical robots, implants, and wearables). In practical uses, it is usually needed to integrate dissimilar materials, such as soft with rigid and electrodes with non-conductors, in the architecture of soft robots for applying mechanical support and electrical connections. Inspired by nature, where dissimilar materials are found with progressive compositional changing (e.g. muscle-tendon-bone), in this research we will develop a novel robotic material with a smooth transition from soft to rigid, embedding a unique capability of interacting with the environment. This soft-rigid hybrid muscle will benefit from a reliable connection to rigid bodies, withstanding diverse mechanical deformation and robust electrical connections.||You may have a background in physics, materials, electronics, mechanical engineering, mechatronics, biomedical engineering or relevant engineering or science degrees.|
|Majid Taghavi||Origami muscle||Lab based||Origami is a technique for folding paper in order to create 3D structures from 2D sheets and thus provides a simple fabrication method for developing sophisticated structures. Origami has been received growing attention in the robotics community because of its potential for miniaturization and reconfiguration. Origami can help robots achieve considerable change in size, and to adapt their shapes in order to undertake tasks such as locomotion and manipulation in a varied environment. In this project, we will use a novel electronic actuation concept to turn the origami structures into active muscles performing a useful task for a robot.||You may have a background in physics, materials, electronics, mechanical engineering, mechatronics, biomedical engineering or relevant engineering/Science degrees.|
|Majid Taghavi||Electric artificial muscle for wearable robotics||Lab based||This project will focus on a new and exciting area of research in soft robotics muscles. Dielectrophoretic liquid zipping (DLZ) is a new actuation concept that can be used as an electroactive artificial muscle. A pair of insulated electrodes contract like a zipper when a high voltage is applied to the electrodes [Majid Taghavi et al, Science Robotics, 2018]. Application of a tiny bead of dielectric liquid (oil) to the zipping area leads to a gigantic force amplification through a synergistic interplay of various physical phenomena. In this research, we will develop a new embodiment of this actuation concept in a soft structure with the aim of reducing the input voltage, allowing it to be used on the human body for restoration and augmentation of motor functions. You will be trained in actuation development, data acquisition, and characterization.||You may have a background in mechanical engineering, mechatronics, robotics, biomedical engineering, materials, and relevant engineering or science degrees.|
|Majid Taghavi||Interactive robotic skin||Lab based||Human can examine structures or areas for size, shape, consistency, texture, and other characteristics simply by moving their fingers and palms over the surfaces. Dexterous movement, flexible and soft architecture, and a variety of sensing capabilities on the skin enable this palpation. In this project, we will develop an interactive composite to act as a robotic skin, allowing for scanning a soft surface and detecting pressure variations applied by the external objects. This new soft robotic composite will be composed of embedded electroactive artificial muscles and tactile sensors.||You may have a background in mechanical engineering, mechatronics, robotics, biomedical engineering, materials, and relevant engineering or science degrees.|
|Majid Taghavi||Multimodal haptic device||Lab based||While audio and visual senses are well targeted by today’s technology, such as in smartphones, the physical sensation (e.g. touch) is poorly addressed, with most modern devices only using vibration to deliver notifications. In this project, you will develop a device that delivers various gentle mechanical stimulation to a person. This device could be used for sending multiple physical sensations or for communication when the user cannot use audio and visual sense or does not wish to be disturbed when busy.||You may have a background in mechanical engineering, mechatronics, robotics, electronic engineering, biomedical engineering, materials, and relevant engineering or science degrees.|
|Reiko Tanaka||Automatic quantification of fungal burdens in histology images using deep neural networks||Desk based||Invasive aspergillosis (IA) is a critical lung disease that is characterised by uncontrolled fungal growth of Aspergillus fumigatus in the lungs. IA occurs in immunocompromised patients, such as patients undergoing chemotherapy, and is treated with antifungal drugs. Due to the increase of antifungal resistance, there is a real need to locate novel treatments. Experiments investigating new IA treatments usually evaluate treatment responses by reported fungal burden. However, the fungal enumeration methods in the community are not standardised, resulting in different quantifications of pulmonary fungal burden, making quantitative evaluation of disease progression often challenging. Quantifying fungal burden in murine models of infection remains a difficult task. The most accurate and sensitive qPCR-based methods cannot capture fungal viability. As a result, the community relies on less sensitive metrics such as conidial forming units (CFUs), which require comparison with histology images. Histological images of murine lung biopsies can give us an idea of disease progression caused by viable fungal burden. However, enumeration of fungal burden, extent of tissue invasion and occlusion of the airspaces is still done manually. Recently, we proposed a fully automated image analysis pipeline to identify the fungal regions on histological images. The histology images are first transformed into different colour space channels that preserve fungi-related colour information. After applying image enhancement methods to accentuate the fungal regions’ pixel intensity, the pixels are clustered by their intensity values to identify the fungal region in the image. The results broadly show good agreement with the reference annotations, achieving an average Dice score of 65% across 5-fold cross-validation with an 80/20 train/test split of a dataset of 33 images.This project aims to further improve this pipeline by utilising deep neural networks to automatically detect and classify fungal lesions into “spores” and “hyphaes” and subsequently enumerate them (number of spores and hyphael length). The student is expected to review, implement, and validate the different stages of the image analysis pipeline using off-the-shelf deep-learning and image analysis software packages for segmentation, classification and quantification of “spores” and “hyphae” regions.|
|Reiko Tanaka||Computational design of antifungal drug treatment schedules||Desk based||tbc|
|Reiko Tanaka||Development of automated evaluation tool for clinical signs of atopic dermatitis using machine learning image analysis||Desk based||Machine learning methods and their application to image processing have shown a rapid progress over the last decades. Automated classification of melanoma malignancy has already achieved a good progress (Esteva et al. 2017, Nature), thanks to the large number of available images (129,450 images used), as well as advances in characterisation of melanoma severity. This project aims to develop an automated evaluation tool for clinical signs of atopic eczema, a chronic skin disease, by applying machine learning methods to the images of the lesional skin sites. It will enable the daily monitoring of the disease symptoms by patients by themselves, without coming to a clinic.Strong programming skills and a good understanding of statistics are required.|
|Reiko Tanaka||Development of computational tools to predict the occurrence of eczema using machine learning methods||Desk based||One of the main difficulties experienced by people with atopic dermatitis (AD, or eczema) is the day to day unpredictability of AD symptoms. Patients and their families are often perplexed by flares appearing out of the blue for no obvious reason. It is difficult to predict when AD flare-ups occur, whether the flare-ups persist or whether they are going to be mild and transient and thus do not require step-up treatments. The aim of this project is to develop computational models that can predict patient-specific dynamics of AD severity, like weather forecasting, in order to develop interventions that may offer AD patients novel ways of better disease control by a personalised medicine approach. Using the existing data from two large published clinical trials in which participants recorded AD severity scores daily or weekly, we will extract patient-specific intrinsic dynamic patterns in fluctuations of the AD severity, by applying model-based machine learning.|
|Reiko Tanaka||Learning from noisy labels by EczemaNet||Desk based||tbc|
|Reiko Tanaka||Mathematical modelling of filamentous fungal growth in vivo||Desk based||Invasive fungal infections are often critical in vulnerable patients, such as immunocompromised patients. Quantifying the extent of fungal growth in murine infections models during infection remains a difficult task. Currently, qPCR methods form accurate estimates of total fungal burden but cannot capture viability, while CFU counts can capture viability but are inaccurate measures of fungal burden. The community currently relies on using a mix of these measures to quantify fungal burden during disease resulting in contrasting quantifications of fungal burden. There remains a real need to understand the viable fungal burden count during disease progression, without which, we cannot accurately assess the effect of anti-fungal therapeutics in the mouse. This project aims to model the latent viable fungal burden count in vivo using the observed qPCR total fungal burden and inaccurate viability data (in CFUs). The student is expected to propose several mathematical models of Aspergillus fumigatus growth in vivo and compare them using state-of-the-art model selection tools. Model development and comparison will be based on various different forms of Aspergillus growth data in vivo obtained by our collaborators (Ms Natasha Motsi).|
|Reiko Tanaka||Mechanistically inspired non-linear mixed effects models of invasive fungal infections||Desk based||tbc|
|Reiko Tanaka||Removing skin colour bias in eczema severity scoring using image-to-image translation||Desk based||Eczema is the most common form of skin disease. The eczema severity is currently assessed by trained clinical staff. However, the subjective nature of assessing these disease signs could be a source of significant inter and intra-observer variability. Our group recently developed EczemaNet, a prototype novel computer vision pipeline using CNN for automated evaluation of eczema severity from camera images (Pan, Hurault et al. 2020). EczemaNet was trained using the camera images that are predominantly from white skin with the under-representation of darker skin tones.This project aims to develop an AI tool to automatically detect the skin colour on each image and synthesise equivalent skin images of other tones of interest by image-to-image translation. Once the model learns the unique characteristics of an image collection (e.g. eczema on black skin) and figuring out how these characteristics could be translated into the other image collection (e.g. eczema on white skin), the model could synthesise an image of white skin from that of black skin and vice versa. The student is expected to review, implement, and validate the image-to-image analysis pipeline using off-the-shelf deep-learning and image analysis software packages for automated image-to-image translation of skin images.|
|Reiko Tanaka||Systems biology approach for cancer immunotherapy: Dynamical mechanisms to turn "cold" tumours into "hot" tumours||Desk based||Immunotherapy is a promising treatment for cancers. Several immunotherapy treatments have already achieved clinical success. For example, checkpoint inhibitors (CPIs) targeting PD1 and CTLA4 achieved up to 11% of cure rates in advanced melanoma. However, its treatment response rates remain low for a majority of cancers. This project aims to apply a systems biology approach to increase the efficacy of CPI therapies.CPI therapy achieves cancer regression by preventing exhaustion of T cells that pre-exists in the tumours but does not exhibit strong antitumour immunity if tumours have few immune cells. One way to improve the CPI efficacy is to convert immune-excluded cold tumours into immune-infiltrated hot tumours, by enhancing infiltration of tumour-specific immune cells into the tumour tissue. Ishihara et al have recently engineered a tumour-homing anti-tumour cytokine IL-12 (Nat Biomed Eng 2020) that turns immunologically cold tumours into hot ones, and demonstrated a high antitumor efficacy of a combination therapy using IL-12 and CPI for cold tumors. However, the actual dynamical mechanisms by which IL-12 converts cold tumours to hot tumours and how IL-12 acts in combination with CPI therapy is still elusive.This project aims to investigate the cellular mechanism of immune cells infiltration during the combined therapy. The student will develop and analyse a computational model of immune cells infiltration based on the results from in vitro and in vivo experiments, to suggest the best timing of adding CPI theraty to achieve the most anti-tumour efficacy.|
|Reiko Tanaka||Systems biology approach for mechanistic understanding of paediatric asthma exacerbations||Desk based||Asthma is the most common chronic disease of childhood, affecting up to 10% of children in Westernised societies and 200,000,000 individuals worldwide. Many factors indicate the importance of the microbiome in asthma. Asthma is rare in rural societies, and its prevalence has been increasing markedly in the developing world as populations become urbanised. Exacerbations of asthma are often precipitated by otherwise trivial viral infections. Our studies have shown that the normal human airways contain a characteristic microbiome that is altered in children and adults with the illness. Asthmatic airways contain an excess of pathogens (which may damage the airways) and also lack particular commensal species that may be necessary for normal airway functions.This project will take a systems biology approach, by combining experiments with primary bronchial epithelial cells, in silico modelling, and clinical data analysis, to elucidate the effects of the airway bacterial microbiome in asthma, and the role of epithelium barrier integrity in disease initiation and control. We already have - a preliminary mathematical model that will be used to quantify the dynamic interactions among pathogen, commensals at the airway surface, the airway barrier and the immune system, - preliminary data from in vitro experiments, and - clinical data to be analysed. The student(s) will conduct several computational methods to identify the model structures and model parameters, using Matlab.|
|Joseph van Batenburg-Sherwood||Experimentally modelling the interactions between red blood cells and endothelial cells in disease||Lab based||"Microvessels, smaller than a hair, are embedded in all living tissues to deliver nutrients and exchange gases. The regulation of microvascular blood flow must be tightly controlled and dysregulation is associated numerous diseases, such as diabetes.
A major mechanism of regulation involves endothelial cells (ECs) that line all blood vessels and sense shear stresses from the flowing blood. ECs then release bioactive compounds that dilate or constrict the vessel to control blood flow. While much research is focused on how ECs are affected by disease, less attention has been paid to how the blood itself changes. Clinical studies have reported the red blood cells (RBCs) of patients with diseases are different, for example they can be less deformable or aggregate (stick-together) more readily. We are interested in understanding how these changes to the blood can affect endothelial cell responses and thus disease progression. To investigate the flow of blood in microvessels, we have developed a specialised micro-particle image velocimetry system for measuring the flow of blood in microchannels that mimic the microvasculature. We have also developed microvessel-on-a-chip models that incorporate both human ECs and RBCs. By using controlled modifications to one or both of the cell types, we can evaluate the interactions between the two. The project may involve aspects of experimental design, cell culture, immunofluorescence microscopy, fluids dynamics measurements and data analysis. Depending on preference of the student, it could focus more on the RBC or EC side of the research."
|Joseph van Batenburg-Sherwood||Technical advancements to a low-cost, high-performance ventilator||Lab based||In response to COVID-19, we designed JAMVENT (see JAMVENT.com), a novel solution to ventilation that can be built using off-the-shelf parts and perform the functions required by ICU ventilators. The technology has potential for both treatment of COVID-19 and long-term use in addressing the global shortage. The current system is designed for adult use and in settings with compressed oxygen and air supplies. To expand the application range of the technology, additional design work is required. This project is a great medical technology design project, and will involve designing, building, testing and evaluating new features for the JAMVENT system. The project would also be guided by Dr Jakob Mathiszig-Lee will, a consultant anaesthetist and clinical lead on the JAMVENT project|
|Julien Vermot||Lowering costs of super-resolution imaging by developing expansion microscopy||Lab based||Primary cilia are essential cellular organelles involved in cardiovascular development and cardiovascular diseases. Primary cilia ultrastructure remains difficult to assess even though it is clear that pathological cilia function stem from abnormal organisation. Super resolution imaging is a key method for imaging primary cilia ultrastructure. Nevertheless it requires complex labelling methods and expensive microscopes. Expansion microscopy (ExM) is a recent and innovative imaging method based on the physical expansion of biological samples, with the aim to reach super-resolution precision with conventional light-microscopes available in most biology laboratories. The principle is that the specimen of interest (isolated organelles, cells, pieces of tissue, â€¦) is embedded in a swellable hydrogel that will physically expand upon water addition. The physical expansion therefore increases the distance between molecules physiologically close to each other, that cannot be distinguished with regular light microscopes.|
|Julien Vermot||Machine learning for 3D segmentation of large datasets to detect normal and pathological hearts||Lab and desk based||Cardiovascular diseases (CVDs) take a huge toll on the world population. An estimated 19 million people died from CVDs in 2010, representing 30% of all global deaths. This project aims at developing a data analysis pipeline allowing to assess 3D tissue shape changes associated with pathological hearts. The student will develop an image analysis method allowing to quantify 3D heart shape robustly using large 3D imaging datasets collected in the Vermot lab. The goal is to develop and train a segmentation network using deep learning in order to achieve 3D image segmentation of large image stacks. A model based approach will be used to quantify the 3D tissue deformation and predict pathological hearts. The project is shared between the Vermot (in vivo cardiovascular imaging) and Bharath labs (3D segmentation and machine learning).|
|Choon Hwai Yap||Computational Modelling of Cardiac Biomechanics and Tissue Architecture to Understand Heart Failure||Desk based||During many heart diseases, the heart remodels and changes its shape, size, and micro-tissue architecture. However, to date, little is known about how these remodeling features affect the heart biomechanics and its ability to function. Our preliminary work has led us to hypothesize that these remodeling changes to the heart brings about an inefficient configuration of the heart, significantly impede function, and is a mechanism that leads to heart failure. However, a more comprehensive investigation is required to validate initial findings, which is the focus of this project. We will use clinically acquired MRI images of cardiac anatomy and myocyte orientations to build realistic finite element computational models of the heart to investigate their function, and investigate the effects of each remodeling feature. An existing database of MRI images of a cohort of cardiomyopathy patients, and an existing finite element model of the heart will be used for the studies. 3D histological imaging of heart samples can further be done to obtain high resolution data to complement MRI images. The student will work with a team of two supervisors, Dr. Sonia Nielles-Vallespin, an expert in clinical MRI Physics and Dr. Choon Hwai Yap, an expert in cardiac biomechanics, so as to gain exposure to both clinical and engineering aspects.||Students with some experience with computational work will be advantaged, but we welcome all students interested to understand heart diseases and computational biomechanics.|
|Choon Hwai Yap||Catheter Intervention in the Fetal Heart to Prevent Congenital Malformations||Desk based||Congenital heart malformations, or heart birth defects, occur to about 1% of pregnancies, and are devastating. There are evidence that these malformations are caused by abnormal blood flow forces in the fetal heart. In recent years, cardiologists investigated using fetal heart intervention, or catheter-based manipulation of the fetal heart, to restore normative hemodynamic conditions, and found that many fetal babies could subsequently avoid having malformed hearts at birth. Here, we propose to study one such procedure, the aortic balloon valvuloplasty, on a specific malformation, the evolving hypoplastic left heart syndrome, and try to understand the biomechanics impact of the procedure, so as to help doctors understand how to improve the procedure. We also hope to build a tool that can help predict outcomes of the intervention, so that doctors can more accurately select patients to minimize unnecessary risks and maximize benefits.Working with pediatric cardiologists in Austria, and other members of our lab, we will analyze 4D ultrasound images of diseased fetal hearts before and after the intervention. Using existing software tools under interactions with our lab members, we will then perform image motion tracking to extract heart motion, and then use this information to build a finite element modelling (FEM) of the fetal left ventricle, to understand what changes in biomechanical and heart function can be brought about by the intervention, and to explore using this FEM tool to predict the outcome of the intervention, using only pre-intervention data.|
|Choon Hwai Yap||Fine Tuning a Novel Hemostatic Bandage for Commercialization||Lab based||During serious wounds, such as automobile accidents, battlefield wounds, terrorist knife wounds, blood loss is the number one reason for death. The next most important cause of death is infection. We recently discovered a new nano-fibrous material that can be an excellent hemostatic material to address these two factors. This material is superhydrophobic, and has extremely repellency of fluids such as blood, so that it can repel blood fluid and prevent it from leaking or seeping out of the wound. Secondly, it causes fast clotting to seal the wound even without soaking up the blood. Thirdly, after clotting, it peels off with extremely small forces. We can remove the hemostatic bandage without re-tearing the wound again, and causing infection. Finally, the materialâ€™s surface structures prevents bacteria attachment to it. This combination of excellent qualities makes the material very suitable for commercialization as a hemostatic medical device. This material is patented, and published in a good journal: https://doi.org/10.1038/s41467-019-13512-8. We now need to perform further tests to optimize the material design, and collect more data for clotting effectiveness, as well as understand the mechanism of clotting better.The work entails designing the physical form of the hemostatic device, fabricate the material with various composition concentrations and testing with human blood to determine clotting effectiness, and performing assays to understand the clotting pathways. He candidate will collaborate with hematology and critical medicine experts, as well as commercialization champions.|
|Choon Hwai Yap||Importance of the Forces of the Heart During Embryonic Heart Development||Desk based||Congenital Heart Malformations affects about 1% of pregnancies, and can be devastating. There are evidence that abnormal biomechanical forces and subsequent abnormal mechano-biology expressions could be responsible for the malformations. For example, fetal aortic stenosis can prevent normal contractions of the heart, and the lack of deformational stimuli may lead to underdevelopment of the ventricle. In this project, we will perform analysis of 4D microscopy images of zebrafish embryonic hearts, and develop a finite element model for this embryonic heart, so that we can characterize the stresses and strains within the embryonic heart. We will study the normal zebrafish embryonic heart and compare it to disease models, and correlate the mechanical environment to their biological expressions, to understand the importance of proper mechanical stimuli on embryonic heart growth. The project will be co-advised by Dr. Yap on the mechanics part, and Dr. Vermot on the biology part.|