2022 Student Cohort

  • Emily Baker

    Aston University

    Cell-free lung model for mycobacterium abscessus 3D-biofilm formation

    Mycobacterium abscessus is an environmental microorganism that has found a deadly niche in the cystic fibrosis (CF) lung. Both adults and children infected with M. abscessus face 18 months of intensive antibiotic intervention, including both intravenous and nebulised formulations which result in severe and traumatic side effects. Furthermore, treatment is often unsuccessful, and patients present with recurrent infections that contribute to the high mortality rate associated with M.abscessus. Additionally, incidence of infections is rising. The bacterial persistence within the lung environment is thought to be attributed to biofilm formation, aided by the thick mucus matrix typical of the CF lung. We have previously developed a 2D in vitro lung model that enables us to assess the efficacy of nebulised antibiotics against M. abscessus. Beyond this, we have identified compounds that potentiate the antibacterial efficacy of known antibiotics when delivered in combination with them. As a next step, we would like to further develop this model into a 3D hydrogel-based system to determine this efficacy in a more physiologically relevant biofilm as would be observed in the CF lung environment. This will provide us with a much clearer understanding of the way in which M.abscessus grows and responds to antibiotic stress within the host lung, and will enable us to further test the efficacy of the potentiator compounds in a cell-free culture system.

    Primary supervisor:

    Dr Jonathan Cox

    Secondary supervisor:

    Dr Patricia Perez Esteban

    Stakeholder:

    Mr Luke Williams, Manchester Biogel

    Funder:

    EPSRC

    Rory Barnes

    University of Glasgow

    Developing DNA-based schistosomiasis blood diagnostics at the point of care in community settings

    In this project, we aim to develop disruptive technologies that enable highly sensitive and specific disease diagnosis, using DNA or RNA signatures, to be carried out on low-cost paper-based microfluidic assay formats, for use within low-resource communities, globally. The overall vision is to translate nucleic acid testing for both infectious and non-communicable diseases onto lateral flow devices, so that they can be used without centralised laboratory facilities. We have previously pioneered paper-based DNA testing, demonstrating its application in rural low-resource settings, and in this project our aim is, working with Global Access Diagnostics, to explore manufacturing solutions, including cassette design, reagent storage and power management, to enable an integrated assay flow. By way of an exemplar assay, we will develop blood based LAMP amplification with either optical or electrochemical outputs for test results to detect schistosomiasis. Such an assay has the potential to address the public health need for schistosomiasis diagnostics that are practical for use in low-resource settings yet can match the sensitivity and specificity of more complex assays. We will explore the efficacy of devices in field studies in Uganda and/or Tanzania, working with healthcare professionals and community leaders to inform the design and operation of the assay.

    Primary supervisor:

    Prof Jonathan Cooper

    Secondary supervisor:

    Dr Julien Reboud

    Stakeholder:

    Dr Emily Adams, Mologic

    Funder:

    EPSRC

    Eleanor Barton

    Aston University

    Development of a novel in vitro vascular model for analysis of blood flow through medical devices

    Cardiovascular disease (CVD) is the leading cause of death globally. The development of grafts, which can be used to patch an injured or diseased section of artery, or replace diseased tissue entirely, are a vital treatment option for many patients.
    To better understand CVD, a model is required which would allow researchers to visualise blood flow through the vascular system. This would include healthy, diseased and treated systems in order to look for markers of arterial wall shear stress and relative residence time which can indicate problems with blood flow and cell degradation.
    Currently, this visualisation is performed using computer simulations, limited experimental setups and/or animal models. The aim of this PhD project is to develop an innovative, optically transparent, geometrically and physiologically representative ‘phantom’ of the human vasculature. This will involve computer-aided-design, model making, 3D printing and material characterisation. The phantom will be used to capture haemodynamics using particle image velocimetry (PIV) alongside traditional sensing technologies e.g. flow sensors.
    This new model could be used in the development of new treatments, replacing animal models and supporting computational simulations. The aim is for this to be approved as a test methodology for regulatory bodies such as FDA and MRHA.

    Primary supervisor:

    Dr Laura Leslie

    Stakeholder:

    Dr Craig MacLean, Terumo Aortic

    Funder:

    EPSRC

    Ella Boswell

    University of Glasgow

    Paper microfluidic diagnostics for human papillomavirus

    We will work with Global Access Diagnostics with a vision to produce self-powered autonomous DNA-based medical devices, bringing high performance assays into communities at the point-of-care. Key will be low-cost technologies that can be manufactured at scale, close to where they are needed most. Outcomes will involve developing innovative methods for detecting rare nucleic acid biomarker signatures in the sample, integrated with frugal digital innovations that will enable self-powered autonomous tests with digital assistance – so ensuring that the tests can be performed by non-experts. Our aim is to produce a test as simple as a pregnancy test or a lateral flow COVID test – but able to perform sophisticated highly sensitive and specific multiplexed diagnosis. The detailed work description will include combining thin film technologies with microfluidics in order to detect multiple biomarkers, as required to identify genotypes of human papillomavirus (HPV), to guide patients towards the appropriate treatment pathway in communities. The project will be carried out in close collaboration with healthcare professionals and members of the community in Senegal or Uganda, to ensure that aspects of PPIE are carefully considered and that the developments are fit-for-deployment, with the possibility of field testing in these countries.

    Primary supervisor:

    Prof Jonathan Cooper

    Secondary supervisor:

    Dr Julien Reboud

    Stakeholder:

    Dr Emily Adams, Mologic

    Funder:

    Aligned

    Imen Boumar

    University of Birmingham

    Screen-printed nanobody switchable sensors for cell therapy process monitoring

    Cell and gene therapies are poised to transform medicine by providing personalized and effective treatments for patients with chronic or life-threatening diseases. However, the complexity and high costs linked with the manufacturing of cell and gene therapy products have been severely constraining market availability and patient accessibility to these life changing therapies. There is an urgent need for innovative technologies that can address current challenges facing cell and gene therapy manufacturing. Major advances are needed in process integrated analytical tools to accurately and reliably measuring in real-time key attributes of cells throughout the manufacturing process. This interdisciplinary project aims to develop disposable, low-cost electrochemical sensor technology for real-time monitoring of cell secreted protein biomarkers. We are combining for the first time the capability to control binding on-demand using switchable receptors with screen-printing technology. Conceptually different from established biosensors where the surface immobilised affinity binding receptors act as passive probes, we introduce sensor devices, which enable active manipulation of single-domain antibodies, i.e. nanobodies. Consequently, analytes can be capture in space and time for detection, allowing the sensor devices to support real-time data capture for different periods of time. It will provide an exceptional opportunity to implement fully automated, robust cell therapy culture processes and bring down production costs, ultimately delivering cost-effective and impactful therapeutics to patients in need.

    Primary supervisor:

    Prof Paula Mendes

    Secondary supervisor:

    Prof Ivan Wall

    Stakeholder:

    Dr Martin Peacock, Zimmer Peacock

    Funder:

    EPSRC

    Justine Clarke

    University of Glasgow

    Engineering the next generation of biologically active vascular grafts

    Vascular grafts have been used for over 50 years and are the established practice for the replacement of any diseased segments of aorta from the aortic valve to the iliac bifurcation. Two of the main clinical problems of these medical devices are the risk of infection and risk of thrombotic stenosis due to the material’s pro-thrombogenic activity which typically lead to new surgeries. It has been hypothesised that the lack of endothelisation of these grafts could significantly contribute to these problems. This project will develop new biomaterials with enhanced biological functionalization using growth factors and extracellular vesicles that maximize the process of endothelisation and develop next generation of vascular grafts. The project will be developed between the University of Glasgow and Terumo Aortic – a world leader in the fabrication of vascular grafts. This is a multidisciplinary project that will work at the interface between materials and cells. The project will allow the student to develop skills in a number of experimental techniques including extracellular vesicle isolation and characterization, characterisation of functional biomaterials, atomic force microscopy, confocal microscopy and cell and molecular biology at the interface between biomaterials and cells. It will also give them significant industrial exposure through close collaboration with and placements at the company.

    Primary supervisor:

    Dr Catherine Berry

    Secondary supervisor:

    Prof Manuel Salmeron-Sanchez

    Stakeholder:

    Dr Niall Paterson, Terumo Aortic

    Funder:

    EPSRC

    Tahmineh Ghari

    CÚRAM – NATIONAL UNIVERSITY OF IRELAND GALWAY

    Bioprinting vascular and immune-enhanced cardiac organoid injury models

    TBC

    Primary supervisor:

    Dr Andrew Daly

    Secondary supervisor:

    Dr Aideen Ryan

    Stakeholder:

    Funder:

    SFI

    Abin Jose

    University of Birmingham

    Developing a 3D in vitro model of the retina to understand and treat age-related macular degeneration

    The development safe and effective therapies for treating age-related macular degeneration, the world’s leading cause of blindness, is a major priority for patients and healthcare providers. This blinding disease is characterized by irreversible loss of central vision due to progressive degeneration of retinal cells within the macula. Translation of new therapies has been limited by the lack of experimental models being able to faithfully mimic the human pathology. Typically, mouse models are used to induce certain pathological features of AMD but they lack a macular and the models are limited to faithfully replicate the human condition. The use of human cell based co-culture systems may offer a significant advantage to using animal models and enable us to model the human disease more closely. Additionally, developing more advanced in vitro models would help to replace the use of animals in research.
    Together with a team consisting of biologists, biomaterial scientists and clinicians, along with input from our industrial collaborator, this PhD project will develop a state of the art in vitro human model to induce and treat AMD pathology. Once developed, this model will be used to screen new therapies to identify candidate agents for further translation.

    Primary supervisor:

    Dr Lisa Hill

    Stakeholder:

    Manchester Biogel

    Funder:

    EPSRC

    Francesca Kokkinos

    University of Glasgow

    Small molecule induced stem cell differentiation

    Use of stem cells has the potential to transform regenerative medicine, if appropriate strategies can be identified for the controlled differentiation of these progenitors. One way to control stem cell differentiation in the lab is to use small signaling molecules like the synthetic steroid dexamethasone. This approach can’t generally be used in patients though, because the required drug concentrations are too high, and would lead to major side effects. We’re trying to overcome this limitation using several related methods, including developing more potent compounds, and exploring the possibility of delivering drugs directly at the site of action. We’ve got some preliminary results that look promising, and hope that you’ll join our team to help carry this work forward.

    Primary supervisor:

    Dr David France

    Secondary supervisor:

    Prof Matthew Dalby

    Stakeholder:

    Dr Michael Jones, Cell Guidance Systems

    Funder:

    University of Glasgow

    Narjes Meselmani

    CÚRAM – NATIONAL UNIVERSITY OF IRELAND GALWAY

    The design and development of an electrochemical device for the detection of soft tissue necrosis

    TBC

    Primary supervisor:

    Dr Manus Biggs

    Stakeholder:

    N/A

    Funder:

    SFI

    Xally Montserrat Valencia Guerrero

    University of Glasgow

    Designing animal-free organoids based on engineered vegetables and protein crystals [VegFold]

    The project aims at developing the next generation of animal-free scaffolds for tissue engineering and regenerative medicine based on material of vegetal origin.
    We address a strategy where plant leaves are decellularized and used as a scaffold to seed human stem cells in. The natural vasculature of the leaf closely resembles the human one, and it offers an intriguing platform to grow perfusable human organoids or microtissues on. Nevertheless, the cellulose wall is inherently poorly cytogenic and this limits the potential of this “vegetal way”.
    We propose to explore an innovative strategy to increase the efficiency of vegetable scaffolds (VegFolds) by engineering the plants to produce the required molecular moieties for the stem cells to adhere to the cellulose scaffold and start proliferating. Moreover, we plan to integrate PODS, a patented technology from the industrial partner Cell Guidance Systems, to support the osteogenic differentiation potential of the scaffold on a longer term

    Primary supervisor:

    Dr John Christie

    Stakeholder:

    Dr Michael Jones, Cell Guidance Systems

    Funder:

    EPSRC