2020 Student Cohort

  • Aleksandar Atanasov

    University of Birmingham

    Creating a 3 dimensional skin substitute to model normal skin, wound healing and scarring using PODS® technology

    Cell Guidance Systems occupies modern research facilities on the Babraham Research Campus near Cambridge. Babraham provides a vibrant research atmosphere for over 1,000 researchers and hosts some of Europe’s most successful biotech companies. In addition to our own well-equipped labs, we have access to shared facilities on the campus.
    PODS® technology is the primary research interest of the company. The company has multiple programs of research and collaborations in areas as diverse as biomaterial development, Parkinson’s disease and osteoarthritis, amongst others.
    The student would become part of the PODS® group and gain fundamental knowledge about PODS® biology. During their time at the company, the student will be expected to produce at least one PODS® protein that they will use in their own research. They will also be expected to work closely in collaboration with our recent KTP Associate – a PhD level materials scientist who joined the company last year.
    In addition to R&D activities, the company has a commercial division which offers research products and services. The candidate will take part in meetings and gain valuable exposure to commercial activities. This will prepare them to understand the commercial world, and will be particularly useful if they remain in academia.

    Primary supervisor:

    Prof. Anthony Metcalfe

    Secondary supervisor:

    Prof. Liam Grover

    Stakeholder:

    Dr. Michael Jones, Cell Guidance Systems Ltd

    Funder:

    EPSRC

    Edward Contreras

    Aston University

    Scaling-up of keratinocyte expansion for the treatment of large burn wounds

    Skin constitutes the first line of defence against disease-causing organisms, but is susceptible to injury such as burns. Several hundred thousand people in the UK sustain burns every year, and hundreds are fatal. Most dangerously, the loss of the barrier to pathogens means that patients can succumb to overwhelming infection – sepsis – within a few weeks after injury.
    The gold standard for treatment is to remove the dead tissue surgically and resurface with new skin. Full-thickness skin grafts are rarely used because there are few donor sites on the body surface, and this thicker skin is less likely to pick up a blood supply at its recipient site. There are several commercially available skin substitutes to replace the epidermis/dermis, or both; however, these options are expensive and have not yielded any acceptable long-term clinical result yet.
    Recent advances utilise cell-based techniques – extracting biopsies from the patient’s skin, isolating keratinocytes and expanding them in laboratory culture. There are important limitations; time constraints, difficulties in achieving sufficient numbers for clinical application, and the possibility of instigating neoplastic change due to components added during the cell culture process.
    This project aims to overcome some of these challenges by implementing novel cell culture techniques in specialised bioreactors. The key aim is to advance culture techniques that allow an optimal, accelerated growth of keratinocytes from an autograft. These expanded keratinocytes will potentially be applied to seal burn wounds, reducing morbidity and mortality after large injuries.

    Primary supervisor:

    Dr. Patricia Perez Estaban

    Stakeholder:

    Prof. Fadi Issa, Nuffield Department of Surgical Sciences/Restore - Charity

    Funder:

    EPSRC

    William Sebastian Doherty-Boyd

    University of Glasgow

    Synthetic niches for haematopoietic stem cell maintenance and genetic manipulation

    The ability to maintain haematopoietic stem cell (HSC) populations in vitro would provide large societal benefit. Haematopoietic cancers, such as leukaemia, arise from genetic alterations in HSCs. The current approach is to kill malignant HSCs and then use bone marrow transplantation to provide long-term reconstituting (LTR) HSC populations to regenerate the blood system. Bone marrow transplantation is, however, a one donor – one patient therapy and donors are in urgent demand. There have been many attempts to maintain LTR-HSCs in vitro, out of the bone marrow niche. However, out of their niche HSCs either die or expand rapidly losing long-term reconstituting phenotype as they grow; these LTR HSCs are critical to provide to patients as they are the cells required to engraft and to repopulate the marrow to produce new blood cells.
    Working with Manchester BIogel’s synthetic Peptigel® hydrogels, this project will focus on bioengineering in vitro HSC niches. Using physical cues such as stiffness and solid-phase growth factor presentation, and biological cues such as other cells, we will develop microenvironments where LTR-HSC populations can be maintained in the laboratory. Being able to conserve LTR-HSC number in vitro is important as it allows us to study and manipulate the cells. For example, in this new project, we will develop CRISPR approaches to edit the stem cells. This is important as e.g. chronic myloid leukaemia is typified by the BCR-ABL mutation. If we can edit out and correct such mutations, then we can envisage ways to repair patients’ cells ex vivo and then provide them back to the patients – removing the cancer and regenerating a disease free blood system with their own cells.

    Primary supervisor:

    Prof. Matthew Dalby

    Stakeholder:

    Prof. Aline Miller, Manchester Biogel and University of Manchester

    Funder:

    Aligned External Funding

    Ibrahim Halilullah Erbay

    CÚRAM – NATIONAL UNIVERSITY OF IRELAND GALWAY

    Development of New Experimental Models of Inflammatory Bowel Disease

    Inflammatory bowel diseases (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract, which comes in two variants, i.e., ulcerative colitis (UC) and Crohn’s disease (CD). The pathophysiology of IBD is still unclear. However environmental triggers, dysbiosis of gut-microbiota and genetic predisposition are causative. Current treatment strategies for UC are highly challenging, as the total drug dose does not reach the inflamed colon, and some drugs are associated with associated systemic toxicity in the event of absorption. Direct targeting of drugs to inflamed sites in the colon offers the potential of avoiding systemic toxicity while achieving therapeutic efficacy. There is a need for more effective treatments for IBD by delivering therapeutics locally to inflammatory sites. A significant limitation in the development of new drugs and drug delivery systems for IBD is the lack of adequate experimental models. Existing models correlate poorly with each other. The results obtained on some models often do not coincide with the results obtained on other models. It should be noted that animal models for this pathology are not optimal and show significant variability. Results obtained in animals cannot be unambiguously used in clinical practice. (Note the ethical aspect. Experiments on animals involve painful injury. Currently there is a clear need to develop new in vitro models. These models should cover all the hierarchical levels of biological systems. At the same time, the existing traditional models on cell cultures will also be used along with new tissue-engineering models.
    A key factor that will integrate in vitro models will be the analysis of data from proteomics and genomics, i.e., bioinformatics. This will allow to solve the fundamental problems associated with the etiology of this disease. In vitro models can be accurately characterized. Their physical and chemical parameters, geometrical dimensions, molecular composition, dose, and time of exposure of drugs are known. These parameters along with the bioinformatics data will allow to develop a digital portrait of this pathology. The purpose of this work is to develop new experimental models of inflammatory bowel disease. Our approach includes 4 models. Among them: monolayer cellular models; biopsy model; a model based on tissue-engineering structures; spheroid-based model. In addition, we will develop research methods for these structural models. These studies include physico-chemical methods, structural and histological methods, immuno-histochemical methods, as well as genomics and proteomics. Ultimately, the use of models and new experimental data will allow a more detailed study of the mechanisms of pathology, as well as the development and testing of new drugs, new drug deliverysystems and new effective therapeutic approaches.

    Primary supervisor:

    Dr Yury Rochev

    Stakeholder:

    Funder:

    SFI

    Anna Maria Kapetanaki

    University of Glasgow

    Label-free physical biomarkers for next generation cell sorting

    Flow cytometry is a cell analysis technique which can make measurements of cells in solution as they pass by the instrument’s laser at rates of 10,000 cells per second (or more). Because of its speed and ability to scrutinize at the single-cell level, flow cytometry offers the cell biologist the statistical power to rapidly analyze and characterize millions of cells. An extension of flow cytometry is the sorting module, allowing physical separation of the cells based on a real-time reading in the analysis module, leading to the effective isolation of sub-populations based on the extent and presence of a specific cellular marker. The current method of single cell sorting are based on fluorescent tags, directed against specific molecular targets. While this approach provides high selectivity and specificity, it is not always possible to find a unique label for a specific biological condition. Recently this limitation has been tackled by means of label-free cytometers, measuring physical parameters of the cells such as the dry mass or the elasticity. The proposed project aims at leveraging the full power of this concept, integrating the analysis with the sorting, and addressing single cell label-free sorting. The new technology will be applied to the isolation of stem cells for regenerative medicine and to the identification of Leishmania infections in the blood. Development of label free techniques will increase the power of the drug discovery pipeline for many conditions from infection, to stem cell therapies to cancer treatments.

    Primary supervisor:

    Dr. Massimo Vassalli

    Stakeholder:

    John Sharpe, Cytronome

    Funder:

    EPSRC

    Chanelle McGuinness

    University of Glasgow

    Bioengineering of Pharma ready bone marrow models for cancer drug screening

    Being able to control haematopoietic stem cell (HSC) growth out of the body, out of their niche, is a major goal of stem cell biology. It would make HSC therapies, such as bone marrow transplant for leukemia treatment, more available by transforming them to become one donor – multiple recipient therapies. It will also allow us to develop in vitro niches to e.g. perform CRISPR on cancerous HSCs to provide autologous curative therapies.
    In our laboratories, we have worked to understand how the partner cells of HSCs in their niche, the mesenchymal stem cells (MSCs), are regulated by materials interfaces. This is important as MSCs, that interact with the extracellular matrix in the niche, control HSC growth and self-renewal through cell-cell interactions and paracrine signalling. The understanding we have developed has enabled us to demonstrate that we can bioengineer in vitro niches where MSCs regulate HSC growth to maintain more of the most regenerative HSCs in culture for longer.
    In this exciting new project, the student will develop 3D niche models for HSC growth using microbeads coated in our novel polymers that control how the extracellular matrix is presented to MSCs in order to produce HSC supportive MSC phenotypes. Further, we will work with our industrial partner, Atelerix, to place these marrow microtissues into their hydrogel systems that allow prolonged cell survival at room temperature. This step will be important for translation of our technologies into Pharma use by making them off-the-shelf, reproducible and easy to use.
    The student will join a thriving lab with good links to clinic and to industry and where they will be provided with world-class multidisciplinary training. This will equip the student well for their next career steps.

    Primary supervisor:

    Prof. Matthew Dalby

    Secondary supervisor:

    Prof. Manuel Salmeron-Sanchez

    Stakeholder:

    Dr. Mick Mclean, Atelerix

    Funder:

    University of Glasgow

    Antonia Molloy

    Aston University

    Optimizing Mycobacterial drug discovery using picodroplet technology

    Tuberculosis (TB) is a disease caused by the organism Mycobacterium tuberculosis which kills 1.5 million people each year and is thought to infect one quarter of the world’s population. Treatment of TB is becoming ever more difficult with the emergence of antibiotic resistance, and this has propagated an urgent unmet need to discover new antibiotics with novel mechanisms of action. The development of high throughput microfluidics has revolutionized the way in which we can discover new antibiotics. In this collaborative, multidisciplinary project, we aim to optimize one such platform for use in screening for antibiotics with activity against M. tuberculosis.
    The successful candidate will be trained by and work with Sphere Fluidics to engineer a platform that is optimized for Mycobacterial drug discovery, controlling various aspects of bacterial culture to produce a platform that is physiologically relevant and suitable for high throughput drug discovery. Subsequently, they will transfer this platform to Aston University to the Mycobacterial Research Laboratory for use in screening a highly valuable set of anti-TB drugs, to discover their activity and investigate their mechanisms of action. The selected student will benefit from cross-disciplinary training in both engineering and biological sciences and have the opportunity to apply that training to develop technology that improves the discovery and development of novel antibiotics.

    Primary supervisor:

    Dr. Johnathon Cox

    Secondary supervisor:

    Prof. Ivan Wall

    Stakeholder:

    Dr. Marian Rehak, Sphere Fluidics

    Funder:

    EPSRC

    Sorour Nemati

    CÚRAM – NATIONAL UNIVERSITY OF IRELAND GALWAY

    Fibrotic Glial Scar Formation and Modulation in Vitro

    The inflammatory response following traumatic spinal cord injury induces formation of a fibrotic scar at the lesion site. Many questions remain regarding the extracellular matrix deposited after spinal cord injury and the inhibitory molecules that are upregulated. This project will focus on matrix deposition by glial cells and leptomeningeal fibroblasts. A novel culture system will be utilized and combined with anti-fibrotic compounds for spinal cord repair. An important focus of this project will involve analysis of cell glycosylation, as glycosylation has been shown to play an important role in many biological processes including tissue repair.

    Primary supervisor:

    Dr. Siobhan McMahon

    Stakeholder:

    Funder:

    SFI

    Jessica Roberts

    University of Glasgow

    Modulating the Surface Immunogenecity of Bone and Nerve Bioengineered Constructs

    Current limitations with the use of biomaterials for complex tissue engineering are centralised on mass transport limitations, vascularisation and host tissue integration. A cornerstone for the applicability and clinical translatability of bioengineered tissues, will be developing a thorough understanding of the interplay between the biomaterial and the host immune system. Biomaterials exhibit intrinsic immunogenicity and are not immunologically inert, activating a foreign body-like innate immune response. Despite recent advances, a clear understanding of the immune reactivity of the host against biomaterials remains elusive. Physiochemical modification of the biomaterials to therefore modulate the host immune response will likely be crucial to the success and onward advances of tissue engineering for reconstructive and regenerative medicine. This PhD project will develop a stable, bioengineered delivery system for the application of immune inhibitory molecules to bioengineered constructs, to induce enhanced immunotolerance.

    Secondary supervisor:

    Prof. Manuel Salmeron-Sanchez

    Stakeholder:

    NHS

    Funder:

    NHS

    Sabah Sardar

    University of Glasgow

    Identification of label-free biomarkers in visceral myopathy

    Chronic intestinal pseudo-obstruction (CIPO) indicate a class of rare gastrointestinal disorders sharing the same symptoms (mainly abnormalities affecting the involuntary, coordinated muscular contractions) but for which a clear and definite genetic marker has not been identified yet. Mistreatment associate to lack of diagnosis is a burden that might hardly influence the development of the disease. Nevertheless, cells extracted from patients appear to share similar phenotype and the proposed study aims at characterizing the physical phenotype (mechanics, morphology) with high throughput to identify a label-free marker that might be prognostic for the disease.

    Primary supervisor:

    Dr. Massimo Vassalli

    Stakeholder:

    Mauro Dalla Serra, The National Research Council of Italy

    Funder:

    Aligned External Funding

    Aoibhín Sheedy

    CÚRAM – NATIONAL UNIVERSITY OF IRELAND GALWAY

    Advanced Immunotherapies and Delivery Strategies for the Treatment of Ovarian Cancer

    Globally, >295,000 women are diagnosed with ovarian cancer (OC) each year and the 5-year survival rate is unacceptably high at 30-50%. There are three main reasons for this high mortality: late detection, resistance to platinum-based therapies and insufficient concentration of the therapeutic at the target. This project aims to address the latter two of these.
    In this project we focus on cell-based immunotherapy for OC. Natural Killer (NK) cells have been shown to kill cancer cells and reduce tumor burden by our group and others in pre-clinical studies of OC, and furthermore have the potential to be used as an off-the-shelf therapeutic. Production of Chimeric Antigen Receptor (CAR) NK cells, targeted to receptors commonly expressed on the surface of OC cells, is hypothesised to further increase this cytotoxicity. Despite a hypothesised enhancement in cytotoxicity modified NK cells still need to concentrate in the peritoneum to exert a potent therapeutic effect. We propose an implantable device for repeated site-specific targeted delivery of immunotherapy. This strategy aims to prolong and evenly distribute the therapeutic agent to the target region while also considering repeated minimally invasive delivery of therapy, ease of placement/insertion, patient comfort and effect on the therapy. The PhD student will develop this concept by designing, testing, optimising and manufacturing CAR-NK delivery devices for both mouse and human/porcine implantation with a focus on translation to the clinic.

    Primary supervisor:

    Dr Eimear Dolan

    Secondary supervisor:

    Prof Gerard Graham

    Stakeholder:

    Funder:

    SFI

    Sundararaman Sugunapriyadharshini

    CÚRAM – NATIONAL UNIVERSITY OF IRELAND GALWAY

    Building a 3D Spatial Spheroid Atlas of Tumour Stromal Interactions

    Research Need: 3D spheroid models greatly enhance our ability to develop ex vivo models of both disease and normal physiology. Much advancement has been made with the use of scaffolds and hydrogels. Once of the next challenges is to create a 3D spatial atlas of the cell-cell interactions that occur with spheroids and in turn human tissues. This will allow is to visualize in 3D the signals that are activated within cells as influenced by their proximity to different cell types, hypoxic regions and nutritional availability and/or drug responses. Suguna’s PhD project will use 3D tumour epithelium-stromal versus 3D normal epithelium-stromal spheroid models to investigate (1) the impact of stromal cells on tumour metastasis, and (2) to develop new methods to visualize protein expression, hypoxic regions, cell morphology while maintaining tissue architecture so that a 3D protein-cell map of the spheroid can be built. This will greatly enhance our ability to confirm the relevance of 3D models to real patient pathological conditions. Research from project supervisor Dr. Sharon Glynn’s laboratory have shown that bone metastatic prostate cancer cells preferentially induce differentiation of healthy MSC to a pro-inflammatory stromal cell that promotes PrCa proliferation and invasion (Ridge et al, 2018). In collaboration with the NIH we are developing CODEX based spatial digital pathology to assess the protein patterns and cellular milieu in triple negative breast cancer patient specimens which we will apply to our tumour-stromal 3D models. Using these models Suguna’s PhD will address the following aims:
    • Establishment of 3D spheroid models of normal/tumour – stromal cell co-cultures
    • Development of multiplexing imaging system that preserves the 3D cellular orientation.
    • Investigation of cellular dynamics of response to therapy in 3D spheroid models
    • Explore the exploitation of the immunosuppressive properties of MSCs by tumour cells for immune tolerance and immune suppression during tumour metastasis & chemotherapeutic response.

    Primary supervisor:

    Dr Sharon Glynn

    Stakeholder:

    Dr. David Wink and Dr. Stephen Lockett, National Institutes of Health, Frederick, Maryland, USA

    Funder:

    SFI

    Alexandre Trubert

    University of Glasgow

    Bioactive hydrogels for stem cell engineering

    Cells need three dimensional environments to grow and to differentiate, and thus efforts have been made to engineer materials that can display adhesion ligands, growth factors and that have controlled properties. ECM-derived matrices, such as Matrigel, are currently widely used and support the growth and function of a wide variety of cell types in vitro. However, Matrigel is an undefined mixture of ECM proteins and growth factors (GFs), with undefined composition undefined, lack of control of mechanical properties and to lot-to-lot variability. Matrigel is widely used as it contains GFs that provide biological activity not yet achieved by synthetic systems. Given this, there is a pressing need to design synthetic matrices that can fulfil the roles of the ECM.
    This project will provide further functionality to Manchester Biogel’s synthetic Peptigel® hydrogels (MBG) by incorporating solid-phase presentation of growth factors into the hydrogels. This will enhance bioactivity of MBG gels to target (a) stem cell differentiation (e.g. BMP-2 to promote osteogenesis) and maintenance of stem cell phenotypes. The PhD project will work to engineer this new family of self-assembling hydrogels that have the potential to recruit and present growth factors. We will also show proof of concept of biological functionality by triggering stem cell differentiation and maintenance of phenotypes.

    Secondary supervisor:

    Prof. Matthew Dalby

    Stakeholder:

    Prof. Aline Miller, Manchester Biogel and University of Manchester

    Funder:

    Aligned External Funding

    Chloe Wallace

    University of Glasgow

    New Hydrogels for Encapsulation and Biomedical Applications

    When producing in vitro models, animal derived matrices such as collagen, lack reproducibility and have a high to batch-to-batch variation. Synthetic peptide hydrogels may offer an effective alternative. These hydrogels are relatively cheap to manufacture, easy to use, and have a defined chemical composition making them highly reproducible. This project focuses on developing novel peptide hydrogels for cell culture. Cell Guidance systems have developed PODs technology which can be attached to the cell scaffolds to allow sustained release of growth factors. This project will be highly multidisciplinary; involving aspects of synthesis, gel formation, characterisation, and using the gels as cell scaffolds.

    Primary supervisor:

    Prof. Dave Adams

    Stakeholder:

    Dr. Chris Pernstich, Cell Guidance Systems

    Funder:

    EPSRC

    Hannah Williamson

    University of Birmingham

    On-Demand Sensors for Cell Therapy Bioprocessing

    The project will include an industry placement with the Cell and Gene Therapy Catapult at Guys Hospital, London Bridge, London. The placement will enable the student to gain an understanding of the roles of process development and analytic/data analysis teams. They will apply their knowledge and the technology generated to a range of scalable bioreactor cell cultures and to gain a deeper understanding of typical industry workflows, by working with one of the leading translational cell and gene therapy institutes in the world. It will also enable the student to understand the wider commercial and R&D ecosystem that underpins the regenerative medicine sector.

    Primary supervisor:

    Prof. Paula M. Mendes

    Secondary supervisor:

    Prof. Ivan Wall

    Stakeholder:

    Dr. Damian Marshall, Cell and Gene Therapy Catapult

    Funder:

    EPSRC

    Matthew Woods

    University of Glasgow

    Droplet based microfluidics for probing the metabolom of cells

    Droplet microfluidics have shown exceptional promise for cell and tissue engineering, single cell study, cell testing and sorting. This typically involves complex experiments, which require a microfluidic platform to be able to perform multiple functions on each droplet. In this project, we will focus on different cell types and examine their behavior when exposed to different environments in order to understand how cells can be influenced and how to cause desired differentiations. This application if highly relevant for cell engineering, as well as medical exposure studies.
    The student will exploit state-of-art microfluidic techniques to design and fabricate new prototypes and devices to probe the response of multiple cell types to different environments. This encompasses the use of established methods like soft-lithography and molding but also requires gaining expertise in more advanced techniques combining microfluidics with optical, dielectrophoretic and acoustical setups. Droplet based microfluidics is essential and the key and the student will become an expert in all aspects of this technology.

    This project will allow us to both probe cell behavior in controlled environments and to look for beneficial cellular responses.

    Primary supervisor:

    Prof. Thomas Franke

    Secondary supervisor:

    Prof. Matthew Dalby

    Stakeholder:

    Dr. Jens Plasmeier, BASF

    Funder:

    EPSRC

    Abigail Wright

    University of Birmingham

    Control of ECM organization and the mechanical environment in a 'Joint on a chip' device

    ‘Organ on a chip’ (OOAC) devices provide new miniaturized culture systems for co-culture of multiple tissues such as in the joint. These tools offer new approaches for screening of new drug targets and for diagnostics in studying disease. These devices organise multiple cell types from complex tissues in potential 3D environments with or without dynamic loading. The development of effective biological scaffold materials for OOAC devices relies on the ability to present precise environmental cues to specific cell populations to guide their position and function. Ordered dynamic nano-scale structures such as fibres in the extracellular matrix can modulate cell behaviors in health and disease. Understanding the role of dynamic environments on joint behaviour is fundamental to these model. In this project, we set out to establish natural gels such as collagen with defined oriented fibre architecture. Using magnetic forces, we will position magnetic micro and nanoparticles in a defined 2-dimensional magnetic array which guides the self-assembly of fibrils remotely and dynamically. These topographic fibres can allow the investigation of fibre orientation during health and disease in the tissues of the joint. In addition, the targeted magnetic nanoparticles (MNPs) can be used to provide mechanical stimuli to the cells remotely in a controlled intermittent manner. In addition, we will deliver different mechanical profiles to cells in the chip through targeted MNPs and design complex load profiles in an chip device..The micro-tissues investigated will be cartilage, bone and tendon.

    Primary supervisor:

    Prof. Alicia El Haj

    Stakeholder:

    Prof. Martyn Snow, The Royal Orthopaedic Hospital

    Funder:

    EPSRC