Engineering degradable, ‘tuneable’ microcarriers for the bulk culture of therapeutically active mesenchymal stem cell.
Cell based therapies using Mesenchymal Stromal Cells (MSCs) are an exciting therapeutic option, using our own cells to both dampen inflammation and promote repair of damaged tissues. Unfortunately, we require large numbers of these rare tissue progenitors for effective therapy, requiring expansion in the laboratory. This can result in loss of their important immuno-modulatory and repair functions due to spontaneous differentiation. We have developed a bioreactor methodology, where cells are expanded on microcarriers to provide a greater surface area for these cells to grow on whilst receiving defined growth conditions required for expansion of large numbers of functional cells.
In this project, you will build on this current knowledge to manufacture new microcarriers which can be optimized to provide both adhesive signals, and ‘tuneable’ elasticity to provide MSCs with the optimal growth surface conditions. This ‘tuneable’ new microcarrier system will incorporate slow release crystals allowing direct delivery of growth factors than can modulate MSC function. Importantly, these carriers will be degradable, allowing easy collection of expanded cells for further testing. This project will provide you with experience of bioengineering, as well as diagnostic assays used to phenotype and functionally analyse expanded MSCs to test their quality and ability to control immune cells. We will also investigate the soluble factors released by these cells in the reactor, such as extracellular vesicles, as these are known to be involved in immunomodulation. This multidisciplinary project will generate a new, customizable microcarrier platform to allow the efficient, standardised expansion of MSCs for use in therapy or scientific research.
Funded project for UK/HOME Students
3D printing of edible biomimetic scaffolds for the engineering of animal muscle tissue
The demand for animal-based foods will increase by 70% in 2050 to meet the 22.5% growth in global population. Yet, 800 million people worldwide already suffer from hunger and malnutrition, and the livestock industry contributes 12-18% of the world’s annual greenhouse gas emissions. Cultivated’ meat is an alternative way to produce meat which is safer and kinder to the animals and the planet compared to traditional methods. Replicating meat in vitro, however, is very challenging because of the complex nature of the final product. Furthermore, cultivated meat needs to match the organoleptic properties of conventionally produced meat in order to gain consumer acceptance. Additive manufacturing using 3D printing has already been explored in tissue engineering for the creation of artificial tissues and organs and therefore holds promise for the fabrication of scaffolds to support the formation of structured cultivated meat products. There are two different approaches to 3D printing in this context: (a) building porous acellular 3D structures which are seeded with cells post-printing; and (b) direct bioprinting of cell-laden biomaterials. Although 3D bioprinting can achieve accurate cell distribution, designing a suitable bioink is not an easy task. This project aims to combine edible polymers and 3D printing to create a scaffold material which possess structural and mechanical properties that support and maintain cellular viability and function, with the production of whole cut cultivated meat as the ultimate goal.
Funded project for UK/HOME Students
Isolation of bone sarcoma biomarkers using novel devices
Although tissue biopsy is irreplaceable in identifying the nature of the tumours and is the current golden standard for cancer diagnosis and evaluation, it still suffers from several limitations. An innovative alternative to tissue-based methods, is liquid biopsy (LB), a minimally invasive approach, which relies on obtaining tumour information from body fluids, such as peripheral blood. Common biomarkers detected by LB are circulating tumour cells (CTCs), circulating tumour DNA (ctDNA), micro RNA and extracellular vesicles (EVs). LBs are already widely recognised as a valuable diagnostic and monitoring tool for cancers, but for sarcomas the technology is lagging behind, mainly due to the rarity and large heterogeneity of these cancer types. The concentration of biomarkers in LBs of sarcomas is very low, and the most commonly targeted ones to date are ctDNAs, because their production is the most frequent event in the course of cancer progression. Unfortunately, however, ctDNAs cannot give insights into tumour heterogeneity. Although alternative biomarkers such as CTCs, can be used to describe many cellular components and provide information about heterogeneity, metastasis and response to treatments, they pose challenges mainly associated with CTC enrichment from a single blood sample, particularly due to their low concentration in patients with early-stage cancer. The aim of this project is to develop a novel, selective, single-use system for the isolation of bone sarcoma biomarkers, such as CTCs and EVs, from whole blood, and enable more efficient disease diagnosis and progression for patients with bone cancers.
Funded project for UK/HOME Students
Translation and Manufacturing
Developing a novel in-situ monitoring system for use in bioreactor driven stem cell expansion; automating cell culture monitoring to ensure optimal growth conditions for therapeutically functional cells.
This project aims to develop an in-situ electrochemical probe for continuous cell culture monitoring within a bioreactor. Cell culture reproducibility can be directly influenced by the reaction environment. Key parameters, such as pH, oxygen, temperature, and nutrient concentration, can be used to indicate cell growth status. Aston university have developed a reliable cell culture methodology using bioreactors to allow expansion of large numbers of therapeutically functional MSCs. This new project will incorporate expertise at Zimmer and Peacock, in order to design and implement a novel in-situ probe to continually monitor culture parameters. Combining expertise from both Aston and Birmingham universities will integrate biochemical, bioengineering and biological approaches and provide a diverse training to the student. Within this project, the student will learn key technologies for sensor manufacturing, engineering design, stem cell culture and diagnostic assays to monitor their function and data analysis of these processes. This project will suit a student who is interested in applying electronical engineering approaches to a biological question, especially refining new sensor devices and their applications.
Funded project for UK/HOME Students
Programming and implementation of a clinical trials visual testing app platform for assessment of advances in tissue engineering
All tissue engineering requires clinical trials prior to licensing and this PhD will develop the tools required to support efficient and detailed clinical ophthalmic metric collection at baseline and at timepoints after treatment. As well as being embedded in the doctoral training centre education and networking, the student will work closely with a start-up medical device company to experience all the stages of medical app development and certification within ISO 13485 to develop a patient management dashboard and modules to conduct visual function tests, utilizing the mobile / smartphones inbuilt camera and sensors. Data analytics will be applied to allow machine learning to aid future clinician decision making for personalized medicine. In addition, the student will develop and clinically validate apps for home monitoring of patients to aid and assess compliance and to give real-work symptomology data.
Funded project for UK/HOME Students
Developing novel bioactive materials for bone cancer applications
Osteosarcoma is a primary bone cancer that typically affects children and young adults. Treating osteosarcoma is extremely challenging, to the extent that survival rates have not improved significantly during the past 30 years. Therefore, safe and effective therapeutic materials are required to improve the clinical outcome. The minimum key requirements for an effective biomaterial targeted toward osteosarcoma therapy are (1) to successfully eradicate any residual tumor not excised during the surgery without being cytotoxic to the surrounding tissue and (2) to provide a suitable platform for the regeneration of new bone.
The aim of this interdisciplinary PhD project is to develop and characterize new bioactive materials to improve clinical outcomes for patients suffering from bone cancer. Materials will developed to provide a control release of key metal ions to selectively induce tumour cell death and simultaneously stimulate new bone growth.
The project will build on previous studies undertaken within our group. The successful candidate will undertake a series of in-vitro studies to fully characterise these materials with the aim of developing and optimising materials for clinical applications. The project is in collaboration with the Royal Orthopedic Hospital, Birmingham.
Funded project for UK/HOME Students
Cell and Tissue Engineering | Translation and Manufacturing
Development of a non-invasive method to profile carotenoid nutritional status in humans
The major challenges of Alzheimer’s disease (AD) are the absence of a cure and rapidly increasing prevalence in the modern society. Emerging research into nutrition’s impact on cognition and brain health across the life span suggest that specific nutrients may preserve cognitive function, slowing the progression of AD. Oxocarotenoids, oxygen-containing carotenoid pigments, are known to counteract oxidative stress and may limit neuronal damage from free radicals. We have shown that a systemic deficit in lipid-soluble carotenoids and tocopherols related to fruit and vegetable intake is associated with AD patients. These data suggested high intake of lycopene- or lutein/zeaxanthin-rich food may be important for reducing the AD mortality risk. Therefore, regular monitoring of circulating levels of oxocarotenoids will provide important information to make recommendations for fruit and vegetable consumption. By using the excellent endogenous fluorescence nature of carotenoids, we recently applied photonics technology to characterise in real-time even subtle changes to carotenoid profile. Dermal carotenoid levels measured using such innovative, non-invasive technology offer a promising alternative assessment method to invasive blood analysis. Therefore, our research will develop a new technology that can be employed directly by those who need it such as physicians, pharmacists, or the patients themselves.
Funded project for UK/HOME Students
Engineering a novel mitochondrial-targeting drug for epilepsy in tuberous sclerosis complex
Tuberous sclerosis complex (TSC) is a rare genetic disease caused by mutations in the TSC1/2 genes. Patients of TSC present with many symptoms; including focal lesions in the brain called ‘tubers’. These tubers are highly epileptogenic; leading to 80% of TSC patients developing severe epilepsy that does not respond to conventional antiepileptic drug. Uncontrolled epilepsy in TSC is incredibly dangerous as it can lead to sudden unexplained death (SUDEP), a major cause of death for TSC patients.
Current treatment option for TSC patients include mTOR inhibitors like everolimus. While everolimus is effective for many other symptoms of TSC, its efficacy for seizure reduction is low. The only remaining treatment option is surgical removal of the tubers; which can be effective but the long-term success rate is variable. Thus, epilepsy in TSC remains an unmet clinical need and is a pressing priority for drug development studies in TSC.
We have identified a mitochondrial enzyme in lysine metabolism as a potential new drug target for epilepsy in TSC. We intend to develop a new drug that targets this enzyme in the brain cells; while minimizing peripheral circulation of these drugs. Thus, this project aims to:
- Design a drug to target this mitochondrial enzyme. This will involve medicinal chemistry, lipid biosynthesis, and packaging of the drug into bespoke mitochondrial-targeting nanoparticles. We will also measure uptake of these lipid nanoparticles using advanced spectroscopy detection.
- Testing the efficacy of this compound on induced pluripotent stem cell (iPSC) model of TSC. We will test the drug effect on: (1) electrophysiological properties of the neuron and (2) electrochemistry readout of mitochondrial reactive oxygen species formation
- Measuring the pharmacokinetic properties of designed compound to ensure availability across the blood-brain barrier
In addition to the research aims above, the student will work with our partner organizations; the Tuberous Sclerosis Association (TSA) and Birmingham Children’s Hospital; to gain the opportunity to work and interact with the TSC patients directly.
This project involves multidisciplinary collaboration and offers outstanding research training opportunity; paired with patient-public involvement (PPI) in research.
Funded project for UK/HOME Students
Cell Sensing and Cell Testing | Drug Discovery | Translation and Manufacturing
Novel portable technology for early-stage dermatological cancer diagnostics (DERMATech)
This project is of a highly interdisciplinary nature, at the interface of microengineering, biophysics and medicine, will focus on developing and engineering new methods for improved and accurate detection and assessment of skin cancers as well as understanding, monitoring and controlling the cellular and tissue responses to therapeutic treatments. Overall aim will be focused on development and clinical validation of advanced device for point-of-care diagnostics: ‘Novel Portable Technology for Early-stage Dermatological Cancer Diagnostics (DERMATech)’.
Skin cancer is one of the leading causes of morbidity and mortality worldwide, with high-complication rates. By engineering novel intelligent micronano-substrates combined with advanced spectroscopic techniques to non-invasively detect and quantify skin cancers at the point-of-care, this project will make important advancements in several fields, envisioned to lead to high-impact publications and patent protection. Designed as a portable, cost-effective platform, such novel technology will allow clinicians to rapidly assess skin at the point-of-need and detect the growth at the in-situ stages before it has become a full-blown skin cancer penetrated below the surface.
The multidisciplinary nature of this project will enable developing strong collaborations and integrating scientific findings with related projects as well as building broad skills-set that will maximize the knowledge and chances in making an impact on the world’s academic and industrial stages.
By diagnosing, monitoring and clinically evaluating patients and better understanding of underlying mechanisms of the diseased tissue and biofluids, the outcomes of this research will lay a platform towards revolutionizing the ways of improving the health and quality of life for millions of people worldwide.
Cell Sensing and Testing | Translation and Manufacturing
Identifying how phosphate balance influences the bone healing process
Bone is a complex tissue. When damaged, it can fully regenerate, regaining its initial structure and properties. Large-scale damage, however, can result in fibrous tissue ingrowth and skeletal deformity. To prevent this, bone defects can be filled with grafting material e.g. calcium phosphate ceramics that drive bone formation (osteoconduction) and trigger de novo bone formation (osteoinduction). This effect arises from localized delivery of orthophosphate ions (PO43-), and codelivery of pyrophosphate ions (P2O74-) significantly enhances this effect.
Identifying why the codelivery of the pyrophosphate ions enhances bone formation is challenging since no established method for simultaneously measuring pyrophosphate and orthophosphate ions in culture exists. We will use electrochemical sensors that can differentiate between orthophosphate and pyrophosphate ions to investigate the process in a novel organotypic model of bone formation that we have developed.
The student undertaking this project will be trained in tissue-culture, micro-XRF, microCT, SEM, immunofluorescence/confocal/light-sheet imaging, “omics” (genomics/proteomics/metabolomics) to understand cell differentiation/signalling in this system. They will work with industrial partners to develop inorganic assays to determine the balance between ortho- and pyrophosphate in solution, to validate the sensitivity electrochemical sensors. This technology will allow identification of optimal bone formation conditions, enabling the intelligent design of regenerative therapies.
Cell and Tissue Engineering | Cell Sensing and Cell Testing | Drug Discovery
Tissue engineering the intestinal microbiome: establishing a manufacturing process for microbial transplant systems.
Ablation of the intestinal microbiome and antibiotic overuse contributes to the increased incidence of modern-day diseases, highlighting the importance of the intestinal microbiome in health and disease. Faecal Microbial Transplantation (FMT) is a new treatment approach that involves transplanting faecal material obtained from a healthy donor into the colon of a patient. The success of FMT in reversing disruptions of the gut microbiome is compelling, with the Queen Elizabeth Hospital and the University of Birmingham UK leaders in the field. We are at the eve of a microbial therapy revolution, however, several key issues of FMT mean it will never become a regulated and accepted medicine used in clinical practice. To overcome these problems, we need to create a synthetic FMT substitute. This project aims to tissue engineer the intestinal microbiome by maintaining synergistic commensals found within FMT while removing pathogens by culturing in ex vivo bioreactors mimicking gastrointestinal conditions yet removing the host that pathogens exploit.
The successful PhD candidate, alongside a team of biological chemists, biomaterial scientists, computational microbiologists and gastroenterologists will adapt and develop a state-of-the-art
model of the intestinal microbiome (MIMic – Model of the Intestinal MICrobiome) to produce synthetic FMT that is compositionally similar to current FMT yet safe. The project offers training in
microbiology, next generation sequencing and bioinformatics, biotechnology, computational biology and biomaterial processing.
*This project is available for UK Nationals only*
Cell and Tissue Engineering | Translation and Manufacturing
Modelling cargo loaded macrophage trafficking across liver endothelium: a new approach to drug delivery in liver cancer.
Cases of primary liver cancer, also known as hepatocellular cancer (HCC) are rising rapidly in the UK and new therapies are urgently needed. Immune therapy has shown promising results and in this project we want to explore the potential of using a specific immune cell called macrophages. Pre-cursor macrophages, called monocytes, are found in our blood circulation but they can leave the circulation and enter organs throughout the body. Macrophages are attractive as a target for immunotherapy as their behaviour can be altered to attack tumours and they can also potentially acts as drug delivery agents because they can engulf particles and transport them to sites of disease. To help their delivery we are studying how macrophages can cross blood vessels through cells called endothelial cells. We will use cutting edge imaging and modelling to see how macrophages cross the liver endothelial cells in different physical environments of fluid flow and endothelial stiffness and assess how efficient this process is when macrophages are pre-loaded with cargo. This project will help understand the physical factors which control macrophages crossing the liver barrier and help to design new approaches to promote macrophage cell therapy for liver cancer.
Development of an imaging system for the 3D imaging of blood vessels deep inside the body using lasers and ultrasound
Are you interested in applying physics and engineering to help develop a new medical imaging technique capable of using lasers and ultrasound to image our blood vessels? Various medical procedures require knowledge of the structure and function of blood vessels. For example, knowing the shape and health status of vessels can guide the safe insertion of surgical stents and grafts to treat conditions such as aortic aneurysm. Mapping out the vasculature is challenging however, because existing imaging techniques typically provide limited spatial resolution and functional information. To address this challenge, this project will investigate developing a miniaturized photoacoustic imaging system. Photoacoustic imaging is an emerging biomedical imaging technique in which pulsed light generates ultrasound waves in living tissues. The technique provides high-resolution images of vessels and other structures. Miniaturizing a system to the sub-mm scale could allow a system to be inserted inside a blood vessel to map out the surrounding vasculature from within. However, this miniaturization is challenging, largely due to the difficulty of making small ultrasound detectors. To address this challenge, this project will investigate the feasibility of using laser-based ultrasound sensors positioned at the tip of an optical fibre. The project will involve sensor fabrication and testing, system design, and a range of optical, ultrasonic, photoacoustic imaging experiments, performed in a context of developing new medical instrumentation.
Synthesis and design of new hydrogels for nerve repair
New materials and repair concepts for peripheral nerve injury are necessary to reduce it’s burden of devastating paralysis and sensory loss, with costs to the individual, their families, communities and national health systems. To address the neurobiology of the injury and improve recovery we look for someone to develop novel scaffold materials combined with commercial systems that release neurotrophic factors. This project aims to deliver new research to direct translation to nerve repair in a collaboration between School of Chemistry and the School of Molecular Biosciences. Due to the interdisciplinary nature of the project involves a wide range of techniques, from small molecule synthesis and characterization, to mechanical and electrical testing of new synthesized materials, cell biology and the unique chance of a placement in an industrial setting.
Beating mesenchymal stem cell senescence with materials that organise growth factors
Mesenchymal stem cells (MSCs) from the adult bone marrow can differentiate into cells that support the regeneration of tissues such as bone cartilage, ligament and tendon. They also have immunomodulatory properties and so are becoming more widely used as ‘drugs’ in transplant procedures to help prevent rejection e.g. in islet transplants and in graft vs host disease. Further, they can support the growth of the blood-forming stem cells of the bone marrow and can have regenerative roles in helping in blood diseases such as leukaemias. Therefore, they have the potential to provide a key role in strategies to underpin a wide range of next-generation disease therapies.
MSCs are isolated from the bone marrow in low numbers (1000s) and yet a cell therapy would require tens of millions of MSCs per dose and forming a company to supply the therapies would require the ability to produce billions of cells in order to meet the demand of healthcare suppliers at a cost that can be justified.
As MSCs grow in culture, out of the regulation of the bone marrow, they change phenotype (differentiate) and age (leading to the stopping of growth – senescence). To provide MSC therapies, both of these hurdles need to be overcome.
We have developed polymers that can control the presentation of extracellular matrix (ECM) proteins that MSCs interact with in the bone marrow in ways that allow for better MSC growth. ECM proteins contain cryptic peptide sequences that, when exposed, allow cell adhesion to them and allow signalling proteins, such as growth factors, to bind to them allowing better control of cell signalling.
In this project, we will study primary human MSC growth in relation to the biological presentation of the ECM proteins with growth factors in order to optimise MSC growth in vitro. We will use both biological (PCR, flow cytometry, qPCR, microscopy) and biomechanical (mechanical cytometry, nanoindentation and Brillouin microscopy) to look for markers of preserved MSC phenotype and senescence (eg stiffening of the cell nucleus). We will also employ transcriptomics (RNAseq) and metabolomics to look for signalling targets that we can inhibit as drug targets to further prevent MSC ageing while promoting MSC expansion.
The project is in collaboration with the industrial partner QKine who develop animal-product free growth factors for stem cells.
Automated cell sorting platforms using AI-assisted RAMAN spectroscopy
We are seeking a highly motivated student to undertake a multidisciplinary project to establish a plug-and-play microfluidic platform for sorting cells based on single cell Raman spectra (SCRS). SCRS contains rich information on the biomolecular composition of a cell, which reflects its type and metabolic function. Coupling SCRS with artificial intelligence and advanced optical imaging provides a powerful tool for discovering cellular traits associated with diseases (e.g. cancer). This project will work with oncology scientists and a global Raman spectrometer company (HORIBA) to discover and sort resistant cells against cancer therapies for downstream studies. This will facilitate the discovery of potential metabolic biomarkers for early cancer diagnosis and screening for potential therapies. The project is highly interdisciplinary, involving collaborations between engineers, cell biologists, data scientists and industry. The student will gain a broad range of skills ranging from microfluidics to imaging methods and analytical techniques.
Development of next generation integrative in-vitro models of the synovial joint
The synovial joint is the home for the development of painful and life-threatening chronic inflammation (arthritis). The synovium is a complex environment, subjected to sustained mechanical stimuli and the natural action of the immune system is not sufficient to resolve the inflammatory insult. Arthritis is a major problem of the ageing population, in terms of life quality and economic pressure on the healthcare system but no effective treatments currently exist, mainly due to the absence of proper model systems that can direct pre-clinical research.
Animal models do not recapitulate the complex physiology of the human synovium, and their use raises ethical other than technical concerns. Existing cellular in-vitro models based on 2D cell cultures are very limited, as they do not include the mechanical stimuli and rarely mimic the viscoelastic properties of the human microenvironment.
With this project we aim to develop a dynamic bioreactor that integrates different mechanical stimuli with a 3D-like cell culture environment. The student will work in collaboration with scientists with different backgrounds, from biology to bioengineering, and with Animal Free Research UK, to design, develop and test an animal-free in-vitro model of human synovium suitable for arthritis research.
Engineered living biomaterials in humanised multiphasic in vitro models – optogenetics to control the dialogue between the immune system and stem cells
The immune system plays a key role in physiology and disease. Macrophages interact with stem cells to enable or prevent regeneration and modulate cancer progression. Macrophages acquire two major phenotypes (M1 and M2) that promote regeneration or inflammation, albeit a number of intermediate phenotypes have also been described at the interface with biomaterials. Here, we will develop multi-phasic in vitro 3D systems to investigate the relationship between macrophage polarization and mesenchymal stem cells. Unconventionally, we will develop living biomaterials – a novel generation of biomaterials that contain genetically engineered bacteria cells – that will be engineered to contain optogenetic bacteria that secrete cytokines in response to light and drive macrophage polarization into defined phenotypes.
The project in multidisciplinary and will develop living biomaterials to control macrophage polarization using light. By using 3D printing, we will develop multiphasic models that organize macrophages and stem cells and will investigate their interaction using light as an external trigger of the system. The models developed will be free of animal products, and will provide a step forward in incorporating and controlling the role of the immune system in advanced in vitro models.
This project is joint supervised by Prof Tom Van Agtmael (firstname.lastname@example.org) and Prof Manuel Salmeron Sanchez (email@example.com)
Cell Sensing and Cell Testing | Drug Discovery| Translation and Manufacturing
Developing RAMAN-based methodology to investigate cell glycosylation signatures
Rheumatoid Arthritis is a chronic inflammatory condition affecting 1% of the global population, but we still lack methods to predict disease phenotype or responses to drugs. Recent results obtained in our lab identify cell glycosylation as a potential target to overcome this scientific impasse.
All living cells are covered by a distinct layer of glycans [or sugars]. We know that a tight connection exists between the dysregulation of glycan expression and the onset of chronic inflammation, but the details of this process are still unclear, mostly due to the lack of suitable analytical methods. We plan to explore the adoption of Raman spectroscopy as an innovative label-free approach to explore the glycocalyx. This tool will shine a new light on the field of glycomics, enabling new scientific discoveries not only to provide more effective ways to investigate pathophysiological changes in cell glycosylation, but also to understand new aspects of cell biology to bridge inflammatory responses, structural glycobiology and mechanical properties of cells both in health and disease.
Moreover, thanks to the collaboration with an industrial leader in Raman instrumentation, HORIBA, we will address the potential of the approach to translate towards the clinic, designing a Raman-powered diagnostic device for inflammatory states.
Smart wearable biosensors for healthcare and wellbeing
As a PhD student, you will work with our partner Zimmer and Peacock Ltd, to develop novel advanced wearable biosensors, which can be used either for healthcare applications or assessing lifestyle and wellbeing markers. The devices, which will either be a watch or a patch/bandage will comprise microfabricated electrochemical biosensors to measure the metabolic activity of the body, non-invasively. The project will be built upon recent innovations to sample both interstitial fluid (ISF) and/or sweat from the skin, using a network of microchannels to carry the fluid to the biosensors. Such advances will dramatically expand the range and number of biomarkers that can be measured simultaneously.
You will obtain experience and knowledge in the development of wearable sensors including those to measure hydration state/electrolytes (important for the elderly and as an endurance exercise tool), pH (characteristic of metabolic disease) as well as more complex analytes including cortisol and adrenaline (for determining stress). Local near-field communications will send and data from the device to a smartphone, where signals will be interpreted using artificial intelligence,run on the GPU to deliver accurate and precise results to the end user.
You will also work with the wider public and other stakeholders (including clinicians) to understand the device design and how the wearable can best be used for healthcare and/or health and wellbeing.
Our partnership with Zimmer and Peacock will provide you with exposure to industrial applications within a vibrant research environment. The new methodologies will be demonstrated through a range of applications, tested in humans.
Organ-on-chip: animal-free methods for drug safety testing
The predictive power of animal tests of new human drugs is poor, so we must find a new and better way to test the safety of new drugs. Our overall ambition is to develop new high throughput methods that advance preclinical testing using advanced human tissue culture with long term aims that will positively impact humans (with safer, more effective medicines), whilst replacing the use of animals in in vivo drug testing.
To achieve this, we will work with our partner, the charity Animal Free Research UK (AFRUK) to transform pharmaceutical testing of new drugs using novel optical spectroscopic methods to probe deep into cell-based constructs of animals’ organs (as a so-called “organ-on-chip). The new methodologies will be demonstrated within pharmacokinetic applications by exploring parameters involved in the metabolism of drugs in the liver (and their toxicity) and/or the adsorption of drugs either across the skin or within the GI tract. The ambition is to provide accurate models of the processes of drug uptake and metabolism in vitro, without using in vivo animal testing.
The project will provide you with experience of working at the interface between the biological sciences and physics/chemistry/engineering, with the opportunity to develop new spectroscopical/optical sensing methods and novel organ-on-chip cell culture techniques. The work will be aligned to the principles of AFRUK, and “organs” will be assembled as spheroid constructs in microfabricated devices using animal free culture methods.
High-throughput electrical characterization of living cells in droplets.
In this project, we will work with our partner Sphere Fluidics Limited to transform single cell analysis by unlocking the ability of electric fields to probe into cellular properties at high throughput. The ambition is to expand cell sensing capabilities, from optical systems, which require cumbersome and complex biomolecular labeling of cells, into rapid and sensitive label-free analysis, which utilizes electrical signatures of cells.
By reducing the need for labels in cell analysis, the project will enable researchers to access cell states outside of the limited characterization afforded by specific molecular markers, which potentially hide significant cell properties and dynamics. The use of electrical measurements within droplet-based devices, also opens up the ability to dramatically increase analysis throughput. Both advantages allow more information to be obtained from in vitro testing on cells, leading to a reduction in in vivo studies towards translation.
The student will have the opportunity to develop novel microfabricated devices for single cells analysis, as well as skills in live cell analysis. Our partnership with Sphere Fluidics Ltd will provide the student with exposure to industrial applications and research environment. The new methodologies will be demonstrated within tissue engineering applications by exploring activation and differentiation of cells driving chronic inflammation.
In situ monitoring of synovial fluid alterations during osteoarthritis progression via impedance spectroscopy
Arthritis describes mild-severe joint inflammation, it is accompanied by structural damage of the joint and leads to severe pain and loss of joint function. Over 100 different types of arthritis have been identified to date, with osteoarthritis (OA) being one of the most common types that globally affects approximately 250 million individuals. As there is no cure to the disease, it is urgent to detect and monitor OA symptoms in situ and in real-time to slow the
progression of the disease and help improve pain and restore joint function. The aim of this project is to generate a bioimpedance sensor that will allow us to monitor synovial fluid (the joint lubricant)
alterations in situ during OA progression and in the long-term to adjust appropriate treatment/injections of proper drugs in real time. The project is a collaboration between the Centre
for the Cellular Microenvironment, the Glasgow Equine Hospital, the Glasgow Small Animal Hospital and Zimmer and Peacock Ltd having renown expertise in biosensors. The project will
develop a novel biomedical tool to (i) answer biolubrication questions (correlation of SF alterations with its lubricating capabilities) (ii) allow early diagnosis and monitoring of disease progression and
(iii) allow appropriate real-time (local) treatment / injection. Overall, it combines a range of techniques from advanced microscopy, impedance spectroscopy and bioengineering.
Exploiting metabolite GPCR mechanotransduction to find new treatments for metabolic disorders
GPCRs are the largest family of membrane proteins and most successful drug targets. Recently a group of metabolite sensing GPCRs has attracted interest in the treatment of metabolic disorders, including obesity and diabetes. In these disorders significant remodeling of adipose tissue occurs, leading to changes in the mechanical properties of the tissue. Although previous work has demonstrated that the function of many GPCRs is altered by mechanical stimuli, very little is known about how these mechanical changes in adipose affect the function of metabolite GPCRs. This project will use advanced microscopy techniques to first define how manipulation of metabolite GPCRs affects the mechanical properties of adipocytes. It will then establish how these changes in mechanical properties alter the signaling profiles of the receptors. Ultimately, this information will be used to establish better cell models and drug screening pipelines that properly account for changes in the mechanical properties of adipose tissue that occur in metabolic disorders.
From the bee’s knees to biotechnology: Resilin-based hydrogels for cell-culture and bioprinting
Hydrogels belong to the most promising materials for cell-culture and tissue engineering. While biocompatibility and degradability of hydrogels are vital for use in cell-culture, mechanical properties have a significant impact on the cell differentiation. Therefore, hydrogel systems with well-controlled and tailorable mechanical properties are highly sought after. The present project will investigate the use of resilin in hydrogel fabrication as an environment for cell-growth with the ultimate goal of tissue engineering. Resilin has remarkable properties (as an elastomer it is literally the bee’s knees), which facilitates the introduction of a broad range of mechanical properties together with crosslinking chemistry, e.g. via carbon nitride in the visible light. Moreover, the project will make use of a modular approach to introduce further functions into the hydrogels in order to enhance cell-growth. Overall, the project will give rise to new robust ‘tuneable’ gels that will address many of the shortcomings of existing cell culture media and will represent realistic alternatives to animal derived materials in research.