Available PhDs

Advertised PhD positions

A number of funding opportunities are advertised by the College for prospective postgraduate research students. Most studentships are advertised between November and January. Specific studentship projects will be advertised by CIR supervisors throughout the year via FindAPhD.com.

Applications can be considered at any time. Eligibility criteria for studentships varies, depending upon the funding source.

Funding opportunities for prospective PhD students

FindAPhD

PhDs Currently Advertised:

The influence of epithelial injury and senescence on kidney fibrosis and patient outcomes

Dr David Ferenbach (The University of Edinburgh)

Characterising host-pathogen impact of light mediated approaches for treating microbial keratitis

Dr Beth Mills (The University of Edinburgh)

GRIN2AC1845A / GluN2AN615K: modelling a severe childhood-onset epilepsy in rats to assess potential therapeutics

Prof David Wyllie (The University of Edinburgh)

Application deadline has passed

Immune cross-talk in rheumatoid arthritis orchestrated by neutrophils

Dr Sonja Vermeren (The University of Edinburgh)

Application deadline has passed Precision Medicine Project

A Personalized Approach - Putting the Squeeze on Mesothelioma

Dr Carsten Gram Hansen (The University of Edinburgh)

Application deadline has passed Precision Medicine Project

Identifying the role(s) of GPR56 and GPR97 in difficult-to-treat acute myeloid leukaemia cells to find new treatments for the disease

Dr Samanta Mariani (The University of Edinburgh)

Application deadline has passed Precision Medicine Project

Meta-analysis of genome wide functional screens to identify broad-spectrum antiviral and immuno-therapeutic targets

Dr Richard Sloan (The University of Edinburgh)

Application deadline has passed Precision Medicine iCASE Project

Dissecting Macrophage-Fibroblast Cell Circuits in Liver Fibrosis using Spatial Omics

Prof Prakash Ramachandran (The University of Edinburgh)

Industrial partner: Macomics Ltd.

Application deadline has passed Precision Medicine iCASE Project

Precision Medicine for Intraoperative Brain Cancer Surgery

Prof Marc Vendrell (The University of Edinburgh)

Industrial partner: EM Imaging

Application deadline has passed EASTBIO (College of Medicine and Veterinary Medicine)

Investigating the role of senescence in ageing and cardio-renal disease in dogs

Dr Katie Mylonas (University of Edinburgh)

Application deadline has passed EASTBIO (College of Medicine and Veterinary Medicine)

Investigating phosphoinositide acyl chain composition as a novel regulator of T cell signalling during ageing

Joy Edwards-Hicks (University of Edinburgh)

Application deadline has passed EASTBIO (College of Medicine and Veterinary Medicine)

Understanding how neutrophils fine tune the immune response to Staphylococcus aureus infection

Dr Clare Muir (University of Edinburgh)

Application deadline has passed EASTBIO (College of Medicine and Veterinary Medicine)

The role of SPZ1 in cancers with deregulated Retinoblastoma (pRb) tumor suppressor protein

Prof Jurgen Haas (University of Edinburgh)

Application deadline has passed EASTBIO (College of Medicine and Veterinary Medicine)

Establishing drivers for the generation and transmission of antimicrobial resistance in the food chain

Dr Thamarai Schneiders (University of Edinburgh)

The influence of epithelial injury and senescence on kidney fibrosis and patient outcomes

Applications accepted up till Monday 17th February, 2025. Competition funded PhD Project.

Supervisors: Dr David Ferenbach (University of Edinburgh), Dr Katie Mylonas (University of Edinburgh), Dr David Baird (University of Edinburgh)

This PhD studentship will decode the interactions between healthy/ injured/ senescent renal epithelia and fibroblasts in human kidney disease and transplantation. We hypothesise that pre-existing and newly generated senescent cells (SCs) in the kidney activate fibroblasts, drive fibrosis and oppose regeneration. Characterising and blocking the SC pathways responsible for these effects should allow their physiological clearance, reduce fibrosis and promote renal regeneration.

Chronic Kidney Disease (CKD) affects around 700 million people worldwide(1). It is one of the top 10 causes of death worldwide, with 3.5 million sufferers and nearly 30,000 patients requiring dialysis for end-stage kidney disease in the UK.

Kidney transplantation is the ‘Gold Standard’ treatment for end-stage kidney disease – offering major increases in healthy life expectancy and lower healthcare costs compared to ongoing dialysis. Unfortunately, demand far outstrips supply, with over 4,700 patients in the UK awaiting a kidney transplant as of March 2022, but only around 2,200 transplants performed annually. Additionally, whilst great advances have been made in overcoming acute immunological rejection of these ‘foreign’ organs over the last four decades, far less progress has been made in treating chronic allograft nephropathy - the gradual loss of function which causes many cases of late graft failure(2). Only 56% of deceased donor transplants are still functioning 10 years post-surgery, with grafts from older living donors having worse function than their younger counterparts(2, 3).

Our group has demonstrated that increased numbers of chronic epithelial senescent cells (SCs) in the kidney promote renal fibrosis and dysfunction – with selective deletion of chronic SCs restoring regenerative capacity and reducing maladaptive repair and fibrosis after subsequent injury(4). Hence, experimental evidence supports SC:fibroblast interactions within the renal fibrotic niche as key determinants of outcome in the diseased native human kidney and renal allografts.

The recent development of single cell resolution spatial transcriptomic analysis facilitates analysis of human kidney disease and the pathways underlying this in unprecedented detail. This PhD studentship will provide instruction and support in the multi-omic analysis of native and transplanted human kidney biopsies. It will also provide comprehensive tuition in the induction, manipulation and analysis of senescent epithelia (in vitro and optionally in vivo) alongside in-depth training in bioinformatic analysis of the data above.

Aims

Human ex vivo/in silico:

Perform single cell, spatial transcriptomic and proteomic analysis of biopsies taken from native human chronic kidney disease and transplantation
Use bioinformatic analysis to explore the impact of senescent cell<>fibroblast signalling on patient/graft outcomes

Human/Murine in vitro/in vivo:

Interrogate candidate senescent cell induction stimuli, their resulting transcriptional changes and signalling pathways
Target the pathological senescent epithelia -fibroblast interactions present in human kidney disease in vitro to reduce fibrosis and promote SC clearance
Learn in vivo models of renal aging and injury to characterise the kinetics of SC induction and clearance in vivo in murine models of kidney disease

Human in vitro:

In collaboration with the Edinburgh Drug Discovery group, the PhD student will receive tuition and support in the use of high-throughput in vitro phenotypic analysis tools to screen libraries of FDA-approved drugs, target annotated tool compounds (including candidates predicted to target the pathways identified as linking to senescent cell persistence, fibrosis and functional deterioration

Training outcomes

The student will receive interdisciplinary training combining

Practical training in single-cell and spatial transcriptomic image acquisition with a post-doctoral research fellow
Tuition in bioinformatic analysis (approx. 50% of PhD) by an experienced post-doctoral bioinformatician.
Training in the use of advanced in vitro culture techniques and analysis by trained lab members and collaborators
In-person and online training and support, including statistical analysis and PhD/research manuscript preparation
Optional: Tuition and support in the use of in vivo models of fibrotic kidney injury to investigate the roles of aging and injury on SC induction and clearance
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

References

Collaboration GBDCKD. Global, regional, and national burden of chronic kidney disease, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2020;395(10225):709-33.
Hariharan S, et al. Long-Term Survival after Kidney Transplantation. Reply. The New England journal of medicine. 2022;386(5):499-500.
Lim WH, et al. Outcomes of kidney transplantation from older living donors. Transplantation. 2013;95(1):106-13.
Mylonas KJ, et al. Cellular senescence inhibits renal regeneration after injury in mice, with senolytic treatment promoting repair. Science translational medicine. 2021;13(594).

The Ferenbach group is located in University of Edinburgh's Institute for Regeneration and Repair (IRR). The IRR has a broad interest in inflammation, tissue repair and regeneration in a range of tissues and settings including the lungs, kidney, liver, pancreas, bowel, bone, joints, skin, heart and brain. The Institute is located at the Edinburgh BioQuarter, a site shared by the Royal Infirmary Hospital and the University's Clinical Research facilities, and a perfect location to translate basic science into clinical therapies.

Funding Notes

The successful applicant will be awarded a Kidney Research UK funded PhD studentship for three years, which includes their stipend at the UKRI rate, tuition fees and contributions towards travel and research costs of the PhD project. Fee waivers for international students are under consideration at the moment, and so international students are advised to check with Professor Ferenbach prior to application.

Apply now

The studentship will be awarded competitively. Applicants should hold at least an upper second class degree or equivalent in a relevant discipline. Applicants should submit the following documents: (i) Personal statement about their research interests and their reasons for applying and (ii) CV to CIR.Postgraduate@ed.ac.uk no later than 12 noon on Monday, 17th February 2025. Please include the project title in the subject line of your email.

As part of the application process, applicants are also required to complete and submit the Online Application Form . Applicants should also arrange for two academic referees to submit letters of reference via email before the deadline to CIR.Postgraduate@ed.ac.uk.

Informal enquiries can be sent via email to Dr Ferenbach: David.Ferenbach@ed.ac.uk

Interviews are expected to take place 2-3 weeks after the closing date for applications.

Characterising host-pathogen impact of light mediated approaches for treating microbial keratitis

Applications accepted up till Friday 7th March, 2025. Competition funded PhD Project.

Supervisors: Dr Beth Mills (University of Edinburgh), Dr Chloe Stanton (University of Edinburgh)

Microbial keratitis (MK) is a significant cause of vision loss worldwide. Current treatment regimens rely on the application of frequent antibiotics or antifungals (up to hourly). Despite these gruelling regimens, ~60% of patients suffer from moderate or worse visual impairment, with ~15% requiring surgical interventions, such as corneal transplant. Alternative treatments are desperately required with higher efficacy.

Light mediated therapies using activatable photosensitisers (PS) for treating infections are gaining traction, with the first pre-clinical and clinical studies utilising photodynamic therapy (PDT) reported for treating MK. However, these used broad-spectrum PS that have off target effects on the surrounding ocular tissue, leading to reported stromal damage. Their efficacy against some pathogens is also uncertain. We have developed and shown initial advantages of “microbe-specific” PS, exploring their use for a more targeted approach to killing bacteria and fungi.

Primary Question:

Does pathogen-specific light mediated killing cause less off-target cell/tissue damage (including leukocytes) in our model systems compared to broad-spectrum PDT?

Aim:

To optimise, evaluate and compare performance of our microbe-specific PS for PDT in in vitro and ex vivo models of MK.

Key objectives:

1. To optimise dosing (formulation, light exposure) for maximal pathogen killing.

2. Measure off-target effects (corneal cells, leukocytes and collagen damage).

Methods:

We have a range of established in vitro 2D and 3D corneal models using cell lines and porcine primary cells for corneal epithelium and stromal keratocytes, and a well-established porcine ex vivo model of MK with bacteria and fungi.

PS formulation and illumination doses will be optimised as part of the programme of work. Microbial killing will be confirmed by colony forming unit. Tissue damage will be monitored by live-dead staining, metabolic activity assays, cytokine release assays.

Anticipated Impact:

Antimicrobial PDT has the potential to alter the treatment pathway for MK patients and improve treatment outcomes. We believe that this pre-clinical work will offer an alternative or adjunct to the sole reliance on antimicrobial eyedrops for the treatment of MK, forming a basis for translation and subsequent clinical evaluation.

Facilities and PhD Training Outcomes:

The research group is located in the Centre for Inflammation Research (CIR), a world-class research centre based within the University of Edinburgh's Institute for Regeneration and Repair. CIR has a broad interest in inflammatory disease and repair in a range of tissues including the eye, lungs, kidney, liver, pancreas, bowel, bone, joints, skin, heart and brain. The Centre is located at the Edinburgh BioQuarter, a site shared by the Royal Infirmary Hospital and the University's Clinical Research facilities, and a perfect location to translate basic science into clinical therapies.

The student will be embedded into IRR’s postgraduate community (>200 students) and PhD training framework. The student will participate in PhD training events at IRR, including journal clubs, poster presentations and scientific writing and oral presentation skills, receiving written feedback from IRR’s principal investigators. They will be assigned a PhD thesis committee within a month of starting, who provide formal (yearly) and informal academic, pastoral and career development support. The student will tailor their education using courses offered by University’s Institute for Academic Development and Edinburgh Innovations to improve study and research skills, and advance personal- and career development. The IRR and UoE’s extensive wellbeing and mental health support resources are introduced during induction and refreshers sessions.

The student has opportunities to interact with patient groups through dedicated patient involvement activities, and with the wider public through established outreach with local schools, science festivals and through at least one visit to project partners, the Aravind Eye Care System (AECS), India.

Funding Notes

The successful applicant will be awarded a 4 year studentship, which includes their stipend at the UKRI rate (AY 2025/26: £19,795) and tuition fees (at the UK home rate or international rate), and contributions towards travel and research costs for their PhD project.

Apply now

The studentship will be awarded competitively. Applicants should hold at least an upper second class degree or equivalent in a relevant discipline (e.g. immunology, microbiology, cell biology), and meet the English language entry requirements. Applicants should submit the following documents: (i) Personal statement about their research interests and their reasons for applying and (ii) CV to CIR.Postgraduate@ed.ac.uk no later than 5pm on Friday, 7th March 2025. Please include the project title in the subject line of your email.

As part of the application process, applicants are also required to complete and submit the Online Application Form. Letters of reference will be requested if you are shortlisted for an interview.

Informal enquiries can be sent via email to Dr Beth Mills (beth.mills@ed.ac.uk).

Interviews are expected to take place 2-3 weeks after the closing date for applications.

GRIN2AC1845A / GluN2AN615K: modelling a severe childhood-onset epilepsy in rats to assess potential therapeutics

Applications accepted up till Friday 7th March, 2025. Competition funded PhD Project.

Supervisors: Prof David Wyllie (University of Edinburgh), Prof Emma Wood (University of Edinburgh)

N-methyl-D-aspartate (NMDA) receptors are a class of ligand-gated ion channel that are activated by L-glutamate, the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Physiologically NMDA receptors play critical roles in fast excitatory neurotransmission and signalling, in neurodevelopment, synaptic plasticity while dysfunctional NMDA receptor function leads failure certain forms of learning and memory, cell death via excitotoxicity leading to neurodegenerative disease, and where there is imbalance in the excitation:inhibition ratios this is thought to be a significant factor that leads to several psychiatric disorders. Importantly for this project impaired NMDA receptor function can give rise to epilepsy.

Fundamental to the normal physiological functioning of NMDA receptors is the voltage-dependent block that is mediated by Mg²⁺ ions – at resting membrane potentials the permeation pathway (i.e. the ion channel pore) of NMDA receptors is blocked by Mg²⁺ and only when the membrane potential depolarizes as a result of increased electrical activity does the pore become permeable to cations, most notably Na⁺, K⁺ and Ca²⁺ ions. Without voltage-dependent Mg²⁺ block, NMDA receptors would be active at rest and this would lead to excessive excitatory drive and uncontrolled neuronal activity and potentially massive seizure activity. Hence, voltage-dependent Mg²⁺ block is critical for normal glutamatergic synaptic function. In recent years many mutations have been identified in GRIN genes (the genes that encode NMDA receptor subunits) which lead to expression of NMDA receptors with either gain- or loss- of function (1).

About the Project

In this PhD project the student will study the effects of a mutation that in humans causes a severe childhood-onset epilepsy (2) and results from the asparagine residue in the GluN2A subunit being replaced by a lysine residue – GluN2A^N615K. Our lab has previously characterized the physiological and pharmacological properties of GluN2A-containing NMDA receptors harbouring this mutation in heterologous expression systems (3, 4) but in this project we will use a transgenic rat model in which half of the GluN2A NMDA receptor subunits express the mutation – thus the heterozygous nature of the expression seen in humans is reflected in the model.

The student will use multidisciplinary approaches to gain mechanistic understanding of how the reduced voltage-dependent Mg²⁺ block exhibited by NMDA receptors expressing GluN2A NMDA receptor subunits leads to pathophysiological signalling in the CNS. The N615K mutation can be considered to be both a loss-of-function mutation (reduced Mg²⁺ block and reduced Ca²⁺ permeability) while at the same time it can be thought of as being a gain-of function mutation as the activity of NMDA receptors will not be inhibited at hyperpolarized membrane potentials. To assess the extent to which these two sides of altered function contribute to dysregulated signalling the student will combine electrophysiological recording from ex vivo brain slices to assess synaptic function and Ca²⁺-imaging to monitor network activity. Moreover, using a variety of pharmacological seizure-inducing paradigms the student will determine whether this pre-clinical model of childhood-onset epilepsy shows either spontaneous seizure-like activity or increased susceptibility to seizure initiation. Finally, using in vivo recording the student will assess whether the extent to which this mutation leads to epileptic-like activity and how such activity can be ameliorated by drug interventions.

About the ERUK-DTC

The ERUK-DTC is a virtual centre with principal investigators researching different aspects of childhood-onset epilepsies, spread across the University of Edinburgh. In addition to your research, you will be trained and nurtured to become an innovative, creative thinker, will be trained in state-of-the-art techniques, will gain insight into the needs and thoughts of patients and their families, and become equipped to engage with audiences within and beyond the research world. As an ERUK-DTC graduate, you will be ideally placed to be part of the next generation of scientific research leaders in childhood-onset epilepsies.

About the Supervisors/PI

Prof David Wyllie has a long-standing research interest in physiology, pharmacology and function of ligand-gated ion channels, particularly those activated by the neurotransmitter, L-glutamate. Through electrophysiological studies, his lab seeks to understand the structure-function properties and physiological roles of the various subtypes of NMDA receptors. In related research he uses pre-clinical models of single gene causes of neurodevelopmental disorders to study the properties of altered synaptic function and to assess the extent to which pharmacological intervention can ameliorate the changes that are observed in such models.

Prof Emma Wood’s research focuses on neural circuits mediating cognition and memory, and how they are affected in rat models of neurodevelopmental disorders such as Fragile X Syndrome and GRIN-related neurodevelopmental disorders. A major focus in the lab is on circuits mediating spatial cognition and spatial memory, which we probe using in vivo electrophysiological recording techniques for measuring the activity of individual neurons and neuronal populations in awake freely behaving rats, combined with behavioural tasks designed to measure specific cognitive abilities. We are particularly interested in how spatially tuned neurons in the brain such as place cells and head direction cells support spatial cognition, memory, and flexibility, and how the juvenile development and function of these circuits are affected in rat models of ASD/ID.

References

Applicants should also arrange for two academic referees to submit letters of reference via email before the deadline to EdNeuro.PhD@ed.ac.uk including “ERUK-NMDA” and your name in the subject. All documents should be submitted no later than 5pm on Friday 7th March 2025. Short-listed candidates will be notified by email.

Funding Notes

The successful applicant will be awarded a fully-funded 3-year ERUK Doctoral Training Centre studentship which include their stipend and tuition fees, and contributions towards travel and research costs.

Apply now

You should hold at least an upper second-class degree or equivalent in a relevant discipline (e.g., cell biology, physiology, pharmacology, neuroscience). Please apply using the form available here and using the code “ERUK-NMDA” for the project code. Informal inquiries can be made to david.j.a.wyllie@ed.ac.uk in advance of the closing date of Friday 7th March 2025.

Immune cross-talk in rheumatoid arthritis orchestrated by neutrophils

Applications accepted up till Thursday, February 06, 2025. Funded PhD Project (Medical Research Scotland).

Supervisors: Dr S Vermeren (University of Edinburgh), Dr Joy Edwards-Hicks (University of Edinburgh)

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which the immune system attacks joints, e.g. in hands and knees, causing pain and disability. ~1% of the UK population suffer from RA, and while there is treatment there is still no cure. Neutrophils, highly abundant immune cells in humans, are essential for fighting infections. Neutrophils are tightly controlled; if this control goes awry as in RA, they can inflict serious host tissue damage. Neutrophils are not only key to the generation of inflammation, but intriguingly also regulate repair processes. Once a threat is eliminated, neutrophils instruct macrophages to turn from pro- to anti-inflammatory. Recent research suggests neutrophils also modulate T cells, which in RA also attack joint tissue. With excessive stimulation, T cells may become ‘exhausted’, a positive thing in autoimmunity. This project hypothesizes that neutrophils have some anti-inflammatory functions even in the inflamed joint in RA. To test this hypothesis, neutrophils from healthy human volunteers will be treated to resemble those in the inflamed joint in RA. Their ability to perform a range of anti-inflammatory functions, alone, and in conjunction with human macrophages and T cells will be examined. The proposed work will help with understanding immune cell cross-talk in RA and may inform the design of improved therapies for people with RA.

This PhD project offers an exciting opportunity to work collaboratively at the Centre for Inflammation Research (CIR), within the new flagship Institute for Regeneration and Repair (IRR) at the University of Edinburgh, and spend 3-6 months at RoukenBio, a Scottish contract research organisation with expertise of in vitro modelling immune cell interplay of complex diseases.

Training outcomes

The student will benefit from the world-leading research environment at CIR, be integrated into the broader CIR PhD programme and embedded in the IRR’s Postgraduate Training Framework. They will have access to state-of-the-art research facilities at IRR and the wider University and receive cross-disciplinary training aimed at equipping graduates will skills to drive future research developments in inflammation research, regeneration and repair. IRR and the University of Edinburgh offer a wide range of training opportunities including general research skills, advanced training courses in specific areas and transferable skills.

Apply now

Full application requirements can be found on FindaPhD. Enquiries should be sent by email to Dr Sonja Vermeren: sonja.vermeren@ed.ac.uk

Apply on FindaPhD

Precision Medicine Project - A Personalized Approach - Putting the Squeeze on Mesothelioma

Applications accepted up to Monday 13th January 2025

Supervisor(s): Dr Carsten Gram Hansen (The University of Edinburgh), Prof Vincenzo D’Angiolella (The University of Edinburgh), Dr Pierre Bagnaninchi (The University of Edinburgh) & Prof Janne Lehtioe (Karolinska Institutet)

Malignant Pleural Mesothelioma (MPM) is an asbestos induced, infiltrative, aggressive and incurable cancer that originates in the pleural lining of the lung. The cancer results in high levels of fibrosis and pleural effusions. Genetic profiling of MPM tumours has unveiled specific but limited set of common loss of function mutations in tumor suppressors. These include prominent mutations within Hippo pathway members and in the deubiquitinase BAP1 (1). MPM patients have a bleak outlook: life expectancy after diagnosis is 1-1.5 years. Current treatment options are not effective and in general can be considered palliative care. Consequently, there is an urgent need for new and enhanced experimental models that replicate the disease in order for patients to access tailored treatment approaches. To this end we will leverage our recently developed and unique isogenic in vitro experimental model (2) to directly determine the tumour stroma’s role and mechanical forces in mesothelioma.

Our cellular models also contain patient derived cellular models including primary cells and organoids. These cellular models are compatible with high content imaging and a microfluidic setup combined with digital homographic imaging (3) that allow us to directly assess how mesothelioma in patients with distinct mutations differ. Targeting loss of tumour suppressors as in mesothelioma is challenging, and we will therefore seek to identify new therapeutic targets, through a targeted CRISPR screen in order to identify new potential therapeutic targets (4). We will carry out proteomics on prioritized KO targets. This combined will give insights into synthetic lethality, dysregulated protein complexes and networks. We expect these will give us new therapeutic targets, that we will directly assess by combinatorial genetic and chemical targeting approaches. In this advanced setup utilizing cellular disease models that represent the heterogeneity among patients, we can mimic critical disease relevant in vivo scenarios thereby evaluate cancerous cells drug sensitivities in scalable high content imaging compatible model systems. Experimental cellular models are in place. These cellular models combined with the unique experimental setups provides us with an opportunity to understand how mesothelioma patients differ, and discover new precision medicine therapeutic targets, that we anticipate will develop into new stratified treatment opportunities.

Aims

Determine the personalized response to changes in the mesothelioma microenvironment
Identify new therapeutic targets, through targeted CRISPR screen
Target identified mesothelioma therapeutic candidates chemically and genetically

Training outcomes

The project includes a range of interdisciplinary skillsets, including genome editing, high content and quantitative imaging, as well as holographic imaging, expertise in bioengineering, biochemistry, primary cell and organoid culture, CRSIPR screen, proteomics workflow and quantitative analysis. The project provides training in Matlab, “R” and Python combined with diverse cross disciplinary techniques and the use of clinically relevant advanced cellular model systems. The studentship includes research stays and workshops at Karolinska, which allows the candidate an international research experience. Opportunities to engage with patient interest groups are available. The candidate will furthermore have access to a suite of professional career development workshops through the Institute for Academic Development, and be part of dynamic, productive and supportive research groups located within the newly established IRR, with focus on research led training in a team environment.

Combined, this safeguards that the candidate upon completion of the PhD will become an agile researcher with a timely, comprehensive, advanced and unique skillset necessary for a successful career in Science.

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

Precision Medicine Project - Identifying the role(s) of GPR56 and GPR97 in difficult-to-treat acute myeloid leukaemia cells to find new treatments for the disease

Applications accepted up to Monday 13th January 2025

Supervisor(s): Dr Samanta Mariani (The University of Edinburgh), Dr Andrew Wood (The University of Edinburgh), Prof Vignir Helgason (University of Glasgow) & Prof Simon Arthur (University of Dundee)

Background

Acute myeloid leukaemia (AML) arises from abnormal proliferation and differentiation of myeloid cells. Current therapies are not curative to all patients and around 40% of patients relapse one year post transplant. There is a strong unmet need to identify novel therapeutic targets for AML.

High-risk treatment-resistant AML patients show a molecular signature with upregulated expression of the G-protein coupled receptor 56 (GPR56). High GPR56 protein expression has been linked to poor survival (<3 years) and higher risk of relapse post transplantation.GPR56 is a 7-transmembrane receptor in the adhesion G-coupled protein receptor family.

At steady-state, the absence of Gpr56 in mouse cells is compensated by the upregulation of Gpr97 (genetically-linked and highly-homologous to Gpr56).

GPR56 is a druggable receptor that might lead to the production of new antibodies for the treatment of GPR56-expressing high-risk leukaemia patients, but their effectiveness might be hindered by a compensatory up-regulation of GPR97, as seen in mouse haematopoiesis. Similar to GPR56, GPR97 has been associated with poor prognosis in AML.

Assessing the roles of and the possible redundancy between GPR56 and GPR97 in high-risk AML cells is needed to further stratify AML patients and to design new drug therapies, such as GPR56 mono- or GPR56/97 bi-specific antibodies.

Hypothesis

GPR56 and GPR97 (aberrantly expressed in subgroups of high-risk AML patients) have redundant/complementary functions in AML cells.

Aim

Define the role(s) of GPR56 and GPR97 in AML, with the final goal of further stratifying high-risk AML patients, and assessing GPR56/GPR97 suitability as druggable receptors for the disease.

Objectives

1Knock-out line generation: To understand if the redundancy between GPR56 and GPR97 is present in leukaemia cells, four leukaemia cell lines, MUTZ-3, MOLM13, MV4-11 and NOMO1 (characterised by different oncogenic mutations) will be transfected (CRISPR/Cas9 constructs) to generate single and double knock-out lines.
Test the effect of GPR56 and GPR97 loss-of-function: Proliferation curves of wild type (WT) and CRISPR-engineered MUTZ-3, MOLM13, MV4-11 and NOMO1 cells will be generated to understand whether the absence of either or both receptors affects leukaemic cell proliferation, and if the effects are mutation specific (i.e. different outputs in different AML cell lines). Progenitor potential/lineage bias, differences in cell cycle and/or apoptosis, and the effect of different anti- cancer treatments (5-Fluoruracil, Cytarabine, Radiation, Daunorubicin) will also be tested.
Define the intracellular signalling pathways of GPR56 and GPR97: The downstream pathways of GPR56 and GPR97 in the haematopoietic compartment are yet unknown. To assess GPR56 and GPR97 signalling directly at protein level, high-resolution quantitative proteomics will be performed on WT and GPR56-/-, GPR97-/-, GPR56-/-/97-/- MUTZ-3, MOLM13, MV4-11 and NOMO1 cells. Results will be validated by flow cytometry and western blotting.
Translation to human primary BM-derived CD34+ leukaemia cells: Thanks to an active collaboration with the Erasmus MC, we have access to microarray, RNAseq and prognosis data of >600 AML patients, among which there are AML patients showing overexpression of GPR56 and/or GPR97. The available data will be integrated with the proteomic data and will be bioinformatically analysed to find specific GPR56/GPR97-related signature(s) to further stratify high-risk AML patients. Moreover, key experiments to validate the data obtained on cell lines will be performed on primary AML samples expressing or not GPR56 and/or GPR97 (4-5 samples per group, Erasmus MC cohort - ethical approval obtained by Prof Delwel at Erasmus MC. Approval number: MEC-2015-155)

Training outcomes

The student will learn different wet and dry laboratory techniques, including but not limited to: Cell culture (both cell lines and primary cells)

CRISPR/Cas9 targeting High-resolution proteomics Bioinformatic analysis of proteomic and RNAseq data Multi-colour flow cytometry Western blotting Proliferation assay Haematopoietic progenitor assay

References

Daga S, Rosenberger A, Quehenberger F, Krisper N, Prietl B, Reinisch A, et al. High GPR56 surface expression correlates with a leukemic stem cell gene signature in CD34-positive AML. Cancer Med. 2019 04;8(4):1771-8.
Yang J, Wu S, Alachkar H. Characterization of upregulated adhesion GPCRs in acute myeloid leukemia. Transl Res. 2019 Oct;212:26-35.
Maglitto A, Mariani SA, de Pater E, Rodriguez-Seoane C, Vink CS, Piao X, et al. Unexpected redundancy of Gpr56 and Gpr97 during hematopoietic cell development and differentiation. Blood Adv. 2021 Feb 09;5(3):829-42.

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

Precision Medicine Project - Meta-analysis of genome wide functional screens to identify broad-spectrum antiviral and immuno-therapeutic targets

Applications accepted up to Monday 13th January 2025

Supervisor(s): Dr Richard Sloan (The University of Edinburgh), Dr Kenneth Baillie (The University of Edinburgh), Dr Finn Grey (The University of Edinburgh) & Dr Robert Young (The University of Edinburgh)

Background

The recent SARS-CoV-2 pandemic has exposed our need for broad-spectrum antiviral therapeutics and also our need to understand variable clinical outcomes in regards viral disease, morbidity and mortality. CRISPR/Cas9 knockout screens or similar have been extensively used in recent years to functionally identify required viral co-factors and regulating immune antiviral factors at the genome scale. Together these provide new leads in identifying viral therapeutic targets, susceptibility factors in patients, and targets for immunotherapy. Our laboratories have been engaged in such screening against viral pathogens such as influenza A virus, SARS-CoV-2 and Pseudorabies virus resulting in the identification of therapeutically tractable viral cofactors such as CMTR1.

However, screening via functional genomics inevitably reveals many potential targets. Equally, when further considering the extensive collective output of other laboratories world-wide engaged in parallel studies, there then exists a vast amount of extant functional data that is minimally exploited. In our own work, we have developed systematic rank aggregation tools to aid target prioritization from identified gene lists such as the meta-analysis by information content (MAIC) algorithm. More recently, we have further developed computational tools to automate ingestion of functional genomic data from published CRISPR/Cas9 screens.

When these approaches are used together, we can combine the collective output of dozens of functional viral screens augmented with our own in-house unpublished data. This allows us to systematically identify the most consistently identified viral co-factors or restriction factors with increased study power. Analysis may be segregated according to virus type, family or at the pan-viral level, allowing nuanced insights to b made. Hits can be crossed referenced to GWAS data to help understand clinical outcomes, while hits can also be followed with systematic meta-analysis of published literature to determine novelty and therapeutic tractability. Collectively, systematic meta-analysis of functional genomic data allows us to identify the most robust targets for therapeutic identification and patient stratification across multiple functional data sets, while simultaneously being able to compare and contrast across virus types. This will allow the identification of novel broad-spectrum antiviral therapeutic approaches.

Aims

The overall aim of this PhD project is to perform a meta-analysis of CRISPR/Cas9 viral functional screen data to identify, rank and then experimentally characterize host gene products that dictate the outcome of viral infection. This includes:

Meta-analysis to identify proviral and antiviral targets across published and in house functional genomic screens.
Meta-analysis tools such as MAIC and data ingestion tools will be employed to identify and initially rank recurring proviral and antiviral targets of importance both across and within viral species. Priority will be given to viral pathogens of pandemic potential.
Secondary ranking and filtering of viral targets through orthogonal omic-level data and meta-analysis.
The target list identified will be further ranked and filtered according to identification in GWAS studies, evolutionary positive selection analysis, defined protein-protein interactions, transcriptomic profiles, and through systematic meta-analysis of published literature.
Experimental sub-screening and validation of identified proviral and antiviral targets using CRISPR/Cas9 knockout

Training outcomes

The project will involve a mix of both computational and wet lab approaches. The ideal candidate will have shown prior interest in computational approaches in biology, but full training will be given in the use of R, working in a Linux environment, use of in-house analysis tools (such as MAIC), transcriptomic analysis and data visualization.

In the laboratory full training will be provided in cell culture, CRISPR/Cas9 screening approaches, viral culture, cloning and plasmi preparation, qPCR, and flow cytometry. At the end of this studentship the student will have all of the necessary skills to seamlessly transition between biological, clinical, and computational elements of biomedical science.

References

Pairo-Castineira E , Rawlik K, Bretherick AD, Qi T, Wu Y, Nassiri I, McConkey GA, Zechner M, Klaric L, Griffiths F, ..., Baillie JK. GWAS and meta-analysis identifies 49 genetic variants underlying critical COVID-19.Nature. (2023); doi:10.1038/s41586-023-06034-3
Bo Li, Sara M. Clohisey, Bing Shao Chia, Bo Wang, Ang Cui, Thomas Eisenhaure, Lawrence D. Schweitzer, Paul Hoover, Nicholas J. Parkinson, Aharon Nachshon, Nikki Smith, Tim Regan, David Farr, Michael U. Gutmann, Syed Irfan Bukhari, Andrew Law, Maya Sangesland, Irit Gat-Viks, Paul Digard, Shobha Vasudevan, Daniel Lingwood, David H. Dockrell, John G. Doench, J. Kenneth Baillie & Nir Hacohen. Genome-wide CRISPR screen identifies host dependency factors for influenza A virus infection.Nature Communications. 11: 164 (2020)
A genome-wide CRISPR/Cas9 screen reveals the requirement of host sphingomyelin synthase 1 for infection with Pseudorabies virus mutant gD–Pass. Hölpe, J. E. R., Grey, F., Baillie, J. K., Regan, T., Parkinson, N., Hoper, D., Thamamongood, T., Schwemmle, M., Pannhorst, K., Wendt, L., Mettenleiter, T. C. & Klupp, B. G. (2021)Viruses. 13, 8, 1574.
Identification of Host Factors Involved in Human Cytomegalovirus Replication, Assembly, and Egress Using a Two-Step Small Interfering RNA Screen. Dominique McCormick, Yao-Tang Lin, Finn Grey.mBio9:3 (2018). https://doi.org/10.1128/mbio.00716-18

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

iCASE PROJECTS

MRC’s iCASE awards provide students with experience of collaborative research with a non academic partner, enabling the student to spend a period of time with the non-academic partner (usually no less than three months over the lifetime of the PhD)

Precision Medicine iCASE Project - Dissecting Macrophage-Fibroblast Cell Circuits in Liver Fibrosis using Spatial Omics

Applications accepted up to Monday 13th January 2025

Supervisor(s): Prof Prakash Ramachandran (The University of Edinburgh), Dr Linus Schumacher (The University of Edinburgh) & Mr John Cole (University of Glasgow)Industrial partner: Macomics Ltd.

Background

This project will use spatial -omics, computational biology, mathematical modelling and functional studies to study how macrophage-fibroblast circuits regulate fibrosis in chronic liver disease (CLD), how these can be therapeutically targeted and how they can improve approaches to stratify patients.

CLD is a global healthcare problem, affecting 1.5 billion people worldwide, with over 2 million deaths per year. Irrespective of cause, chronic liver damage can lead to scarring or fibrosis, ultimately progressing to cirrhosis and organ failure. The degree of fibrosis is the best-known predictor of adverse clinical outcomes in CLD, meaning there is huge interest in developing new antifibrotic treatments. No such therapies are currently available. Therefore, a more comprehensive understanding of the mechanisms orchestrating fibrosis is needed to inform precision medicine for CLD.

In liver fibrosis, scar-producing fibroblasts and monocyte-derived macrophages accumulate in areas of scarring, termed fibrotic niches. Single-cell RNAseq (scRNAseq) studies have identified disease-associated macrophages and fibroblasts (1). Interactions between these populations within the fibrotic niche might regulate fibroblast proliferation and activation (2). However, spatial information is lost in scRNAseq studies, meaning direct evidence of the molecular mechanisms regulating macrophage-fibroblast interactions in the liver fibrotic niche is lacking. High-resolution spatial -omics approaches promise to address this, for the first time enabling the in situ detection of which cell types, molecules and pathways are active within this niche.

Cell interactions in a tissue can be described as ‘cell circuits’ with dynamical systems theory using differential equations (3). Modelling of fibroblast-macrophage circuits has suggested that inflammatory fibrotic neighbourhoods, termed “hot” fibrosis, show greater scope for remodelling and therapeutic manipulation (3). However, these circuit models have been based on simplified data without the full understanding of which ligands and receptors are expressed by scar-associated macrophages and fibroblasts in in situ. Newer computational approaches based on tissue-level spatial cellular neighbourhood data (4) provide a framework to dissect the complexity of the fibrotic niche and link it to interpretable predictions of how macrophages can be targeted to abrogate fibroblast proliferation and activation.

Aims

Generate spatial -omics data (RNA and protein) on liver biopsy tissue from patients with different causes and stages of fibrosis.
Computational analysis of spatial -omics data to identify the cellular and molecular composition and of the liver fibrotic niche.
1. Detailed phenotyping of macrophages and fibroblasts within the fibrotic niche and integration with existing scRNAseq data
2. Cellular neighbourhood analysis to define features of “hot” fibrosis in the human liver
Construct mathematical cell circuit models of macrophage-fibroblast interactions in the fibrotic niche, informed by spatial -omics data (e.g. using One-Shot Tissue Dynamics Reconstruction
1. Perturbation modelling of cell circuits to study effects of candidate therapeutic interventions on fibroblast proliferation and activation
Target identification, patient stratification and functional validation
1. Collaborate with industry partner (Macomics Ltd. to identify tractable targets to modulate macrophage-fibroblast interactions
2. Assess which cell-circuits are enriched in CLD patients with adverse clinical outcomes using established disease cohortsFunctional studies testing cell circuit modulation using in vitro macrophage-fibroblast co-culture models

Training Outcomes

The student will get interdisciplinary training comprising laboratory science, bioinformatics, mathematical modelling and statistics. They will also gain industry experience with Macomics Ltd., learning to translate research findings into potential therapeutics and biomarkers.

Spatial -omics platforms will include CosMx/Xenium and PhenoCycler-Fusion, building on existing data from the Ramachandran lab. The Cole lab will provide expertise in bioinformatic analysis of spatial data. The Schumacher group will support the mathematical model. Target identification and functional validation will be done in collaboration with Macomics Ltd. and based on models, assays and samples available in the Ramachandran lab and/or at Macomics.

References

Ramachandran P, et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level. Nature. 2019;575(7783):512–518.
Bhattacharya M, Ramachandran P. Immunology of human fibrosis. Nat Immunol. 2023;24(9):1423–1433.
Adler M, et al. Principles of Cell Circuits for Tissue Repair and Fibrosis. iScience. 2020;23(2):100841.
Somer J, Mannor S, Alon U. Temporal tissue dynamics from a single snapshot. bioRxiv. 2024;2024.04.22.590503.

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

Precision Medicine iCASE Project - Precision Medicine for Intraoperative Brain Cancer Surgery

Applications accepted up to Monday 13th January 2025

Supervisor(s): Prof Marc Vendrell (The University of Edinburgh) & Prof Paul Brennan (The University of Edinburgh)Industrial partner: EM Imaging

Background

Glioblastomas are one of the most common and aggressive brain cancers. Current treatments provide a mean survival of 14 months, with most tumours recurring post-resection. Optical agents to aid resection are penetrating routine clinical use but improvements are needed in both sensitivity and specificity to better identify and remove malignant cells. Our strategy is to harness the metabolic signature of tumour cells to develop a molecularly-targeted approach for safer and more precise intraoperative resection of brain tumours. The ability to accomplish this has been hindered by the lack of molecular tools that retain the properties of natural metabolites. We have now invented a new class of non-invasive optical agents that function as both fluorophore and photosensitizers, enabling effective optical imaging and light-induced resection. We aim to perform a metabolomic study of patient-derived glioblastoma cell lines that will allow us to identify metabolites that are highly taken up and create optical agents that will be tested fresh tumour tissue samples from surgical resections. We will finally prepare for translation and clinical readiness of the lead compounds together with EM Imaging enabling us to move this technology into early phase clinical trials to provide patient benefit as quickly as possible.

Aims

Our main aim is to combine metabolomics, chemistry and imaging to develop a panel of biomarkers to characterise metabolic signatures of glioblastoma and translate them into a decision-making tool for high precision brain cancer surgery.

Training Outcomes

Generic and transferable skills provided by the supervisory team:

Development of an in vitro metabolomic platform for the selection and optimisation of agents.
Data analysis and management, mining skills and bioinformatics.
Design and characterisation of light-activatable metabolites.
Cell culture, microscopy, flow cytometry, functional assays and immunohistochemistry.
Assessment of optimal agents in ex vivo human tissues.
Image analysis (qualitative and quantitative).
Research ethics and health and safety skills.
Target Product Profile based on current standard of care, health economics data and technical feasibility (with Medical Innovations Team and EM Imaging).
Participation in the development of marketing strategy through competitive landscape and future emerging technologies (with EI and EM Imaging).
Study IP landscape and freedom to operate. Secure emerging IP, including paper and patent writing.
Communication skills.
Training in GMP-compliant facilities

Apply Now

Click here to Apply Now

The deadline for 25/26 applications is Monday 13th January 2025
Applicants must apply to a specific project. Please ensure you include details of the project on the Recruitment Form below, which you must submit to the research proposal section of your EUCLID application.
Please ensure you upload as many of the requested documents as possible, including a CV, at the time of submitting your EUCLID application.

Precision Medicine Recruitment Form (878.42 KB / DOCX)

EASTBIO (College of Medicine and Veterinary Medicine)

Investigating the role of senescence in ageing and cardio-renal disease in dogs

Applications accepted up to Friday 17th January 2025

1st Supervisor: Dr Katie Mylonas (University of Edinburgh)

About the Project

Cells can become old or ‘senescent’ with age and disease. These senescent ‘zombie’ cells are long-lived, metabolically active and release chemicals that drive inflammation and scarring as well as limiting tissue healing. Senescent cells accumulate in organs, including the kidney and heart with age and disease, and are detrimental to function. For example, senescence levels in transplanted kidneys negatively correlate with how well they perform and last. Eradicating senescent cells dramatically increases healthy lifespan in mice. Our research in mice has shown that using senolytic drugs that kill senescent cells before kidney injury leads to less scarring, preserved kidney tissue and better kidney function (Mylonas et al, Science Translational Medicine, 2021). Senolytic drugs are now in phase 2 clinical trial in patients with chronic kidney disease (CKD; NCT02848131).

CKD increases with age in humans. Dogs > 12 years old are also much more likely to develop CKD and our unpublished data demonstrates senescent cells in kidneys from aged dogs. Despite being an active research area in human disease, there is minimal knowledge about senescence in canine CKD. Other chronic conditions also increase with age and in about a third of dogs with CKD, it combines with heart disease to cause death and disability, referred to as cardio-renal disease. Our work suggests that senescent cells are a key link between kidney and heart disease, as mice with injured kidneys exhibit both senescent cells and scarring in their hearts. This may go both ways as our collective research indicates that a common canine cardiac disease called myxomatous mitral valve disease can drive kidney injury. This heart/kidney link merits further exploration.

Close collaborators have identified 2 urinary biomarkers that tightly correlate with kidney cell senescence and scarring on kidney biopsy in human CKD and importantly predict clinical outcome. Intriguingly, one of these biomarkers is linked to canine CKD severity. In this project, we will determine whether these urinary biomarkers of cellular senescence are conserved in dogs or perhaps whether there are additional senescence biomarkers unique to dogs.

During this PhD project we will use commercially available canine cells and tissue/urine provided by the University of Edinburgh companion animal biobank to identify and characterise canine senescent cells (kidney, heart) in vitro and in vivo by established methods, and explore the hypotheses that the tissue senescent cell burden correlates with disease severity and that biomarkers of senescence in canine kidney are detectable in the urine.

Funding Notes

UKRI-funded studentships are open to students worldwide and will cover tuition fees at the UK rate, plus a stipend to support living costs and an annual research grant of £5,000 for the first three years of the PhD research. The proportion of international students appointed through the EASTBIO DTP is capped at 30%. All students must meet the eligibility criteria as outlined in the UKRI guidance on UK, EU and international candidates. This guidance should be read in conjunction with the UKRI Training Grant Terms and Conditions, esp. TGC 5.2 & Annex B.

Apply Now

EASTBIO Webpage (to download the documents required for email application process, detailed below)

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms can be downloaded via link above

Please send your completed EASTBIO Application Form and EDI survey along with a copy of your academic transcripts to CIR.Postgraduate@ed.ac.uk before the deadline.

You should also ensure that two references have been sent to CIR.Postgraduate@ed.ac.uk by the deadline using the EASTBIO Reference Form.

The EASTBIO team will run a series of 1-hour online sessions in December 2024, open to applicants who have queries about the application process. Please view EASTBIO How to Apply webpage for details.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

EASTBIO (College of Medicine and Veterinary Medicine)

Investigating phosphoinositide acyl chain composition as a novel regulator of T cell signalling during ageing

Applications accepted up to Friday 17th January 2025

1st Supervisor: Dr Joy Edwards-Hicks (University of Edinburgh)

About the Project

Healthy life expectancy is declining in the UK, particularly in deprived areas where the number of years spent in good health can vary by up to 26 years. The immune system is the body’s defence against infections and cancer, and a decline in immune system function contributes to increased disease burden in the elderly.

Challenge addressed by the project

T cells form a critical part of the adaptive immune system, important for killing infected or cancerous cells. T cell activation through the T cell receptor (TCR) and co-stimulatory receptors is hampered in older individuals, leading to poor downstream signal transduction, defective metabolic reprogramming, and reduced effector function. To address this decline in T cell response in the elderly, this project investigates a novel mode of phosphoinositide regulation mediated by acyl chain composition. Phosphoinositides are a small family of bioactive lipids with key roles in signal transduction downstream of the TCR. While regulation of phosphoinositides through phosphorylation of the inositol headgroup is well-established, regulation through acyl chain composition, which is dependent on cell metabolism, is of rapidly growing interest with relevance across multiple areas of cell biology. Dysregulated metabolism is a hallmark of ageing, but how this affects phosphoinositide acyl chain composition and interlinked signal transduction is unknown.

Aim

The aim of this project is to mechanistically investigate how phosphoinositide acyl chain composition regulates phosphoinositide dynamics, interlinked signal transduction, and cell function in aged human T cells.

Model

T cells will be isolated from healthy human blood samples using age-matched male and female samples to compare age- and sex-driven phenotypes (ethics approved, sample size determined with power calculations).

Objectives

1. Elucidate how ageing impacts T cell phosphoinositide acyl chain composition and phosphoinositide dynamics.2. Determine how acyl chain composition regulates phosphoinositide-protein binding and signal transduction. 3. Determine whether phosphoinositide acyl chain composition can be targeted to improve aged T cell function.

Key techniques

• Liquid Chromatography-Mass Spectrometry (LC-MS)• Flow cytometry• Processing human blood samples• T cell phenotyping

Potential applications and benefits

By understanding the basic biological mechanisms that underpin dysfunctional T cell signalling in the elderly, this project aims to improve immune system health as a strategy to increase healthy life expectancy.Informal project enquiries are encouraged and can be made to: J.EdwardsHicks@ed.ac.uk.

Funding Notes

Apply Now

EASTBIO Webpage (to download the documents required for email application process, detailed below)

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms can be downloaded via link above

Please send your completed EASTBIO Application Form and EDI survey along with a copy of your academic transcripts to CIR.Postgraduate@ed.ac.uk before the deadline.

You should also ensure that two references have been sent to CIR.Postgraduate@ed.ac.uk by the deadline using the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

EASTBIO (College of Medicine and Veterinary Medicine)

Understanding how neutrophils fine tune the immune response to Staphylococcus aureus infection

Applications accepted up to Friday 17th January 2025

1st Supervisor: Dr Clare Muir (University of Edinburgh)

About the Project

Neutrophils protect us from infection by engulfing prey into membrane bound vesicles called phagosomes. Phagosomes become highly microbicidal environments following the tightly regulated delivery of microbial effectors to the phagosome. This process is co-ordinated by the lipids that form the phagosome membrane and there is growing evidence that phagocytes alter lipid-signaling in response to prey. However, how pathogen processing is controlled and how this adapts to different microbes remains a major gap in our knowledge.

This project will use the optically transparent larval zebrafish to image the recruitment of lipid- reporters to the phagosome membrane of neutrophils during a live S.aureus infection. Key bacterial components that trigger changes in phagosome lipid composition will be identified with support from Prof Ross Fitzgerald, a world leading expert in S.aureus pathogenesis. Phagosome maturation will be measured using pH/ROS sensitive dyes and fluorescent markers of proteolysis which together will inform our knowledge of how prey digestion changes following alternations in lipid-signaling. The functional consequence of changes in phagosome fate will be assessed by using zebrafish that lack or gain function of specific lipid signaling pathways. This will allow the student to interrogate the whole-body immune response to S.aureus infection and therefore identify key signaling pathways that could be manipulated to improve pathogen killing and/or inflammation resolution. An in vitro model of lipid signaling in neutrophils will also be developed in parallel, with guidance from Professor Sarah Walmsley, a world leading expert in neutrophil biology. Together, these models will provide key insights into how neutrophils fine tune the immune response to S.aureus infection.

This studentship would best suit a biologist with enthusiasm and experience of imaging, microbiology and/or immunology. However, we do not expect candidates to have all the relevant skills for this studentship and we will provide training in imaging, zebrafish husbandry, and transfection as required. This project complements a recently awarded Wellcome Discovery Award and as such the student will work closely with our team members at the University of Sheffield.

Funding Notes

Apply Now

EASTBIO Webpage (to download the documents required for email application process, detailed below)

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms can be downloaded via link above

Please send your completed EASTBIO Application Form and EDI survey along with a copy of your academic transcripts to CIR.Postgraduate@ed.ac.uk before the deadline.

You should also ensure that two references have been sent to CIR.Postgraduate@ed.ac.uk by the deadline using the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

EASTBIO (College of Medicine and Veterinary Medicine)

The role of SPZ1 in cancers with deregulated Retinoblastoma (pRb) tumor suppressor protein

Applications accepted up to Friday 17th January 2025

1st Supervisor: Prof Jurgen Haas (University of Edinburgh) & Dr Kate Cushieri (NHS Scotland)

About the Project

In many cancers the Retinoblastoma tumor suppressor protein pRB is either mutated or inhibited. This includes cancers that are caused by persistent infection with high risk Human Papillomaviruses (HPV) such as cervical cancer, which is one of the most frequent cancer in women world-wide. HPV encodes two major oncogenes which cause transformation, E6 and E7. E7 interacts with pRb and leads to it’s degradation. In previous work we showed that the host protein SPZ1 interacts with E7 and counteracts it’s function, leading to an increased half-life of pRB. Intriguingly, SPZ1 is not only expressed within the cell, but also secreted via a non-classical secretion pathway. We were able to show that secreted SPZ1 is also able to act on neighbouring cells and increase the pRB stability in them. Like many growth factors, SPZ1 is expressed at high levels during the embryonal development and might play a regulatory role at some stages of development. In this project, we will investigate the role of SPZ1 in different cancers, and the mechanisms of how SPZ1 stabilizes pRB and inhibits cellular transformation. It will also be investigated whether recombinant SPZ1 can be used as a therapeutic in cancers with mutated or deregulated pRB, both in-vitro as well as in animal models. We will apply a broad range of different molecular, biochemical and cellular methods and use cutting edge new technologies including CRISPR/Cas9 gene editing, next generation sequencing and organoid cell cultures.

Funding Notes

Apply Now

EASTBIO Webpage (to download the documents required for email application process, detailed below)

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms can be downloaded via link above

Please send your completed EASTBIO Application Form and EDI survey along with a copy of your academic transcripts to CIR.Postgraduate@ed.ac.uk before the deadline.

You should also ensure that two references have been sent to CIR.Postgraduate@ed.ac.uk by the deadline using the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

EASTBIO (College of Medicine and Veterinary Medicine)

Establishing drivers for the generation and transmission of antimicrobial resistance in the food chain

Applications accepted up to Friday 17th January 2025

1st Supervisor: Dr Thamarai Schneiders (University of Edinburgh) & Dr Kate Cushieri (NHS Scotland)

About the Project

Pathogenic microorganisms pose a significant threat to food security and in the spread of infectious diseases, particularly the transmission of antibiotic resistant organisms (ARO) which remain a critical concern1. The drivers for the selection or maintenance of ARO’s within the environment represents an important route for the dissemination of these organisms via the food chain. As such, the occurrence and presence of ARO’s in the environment can arise simply as a result of selection by endogenous antibiotics, or the application of antibiotic or antibiotic-like compounds within the environment1. As such, recent data reveals that the genetic factors which contribute to pesticide resistance also confer antibiotic resistance2. Despite this evidence, little is known about the impact of pesticide exposure and the potential for the development of antimicrobial resistance in common microorganisms found within the foodchain. In this application, our overarching aim is to establish a mechanistic basis for pesticide exposure and the transfer of AMR organisms from the environment into the food supply; where the specific aims are to (1) develop and validate a relevant model system to evaluate the selection and transmission of ARO’s (2) determine using an “omics” approach the impact of commonly used agricides in the generation of mutations linked to both pesticide and antibiotic resistance (3) Using in-vivo models establish if microbial transmission and persistence is enhanced in pesticide-exposed plants.This project is led by the University of Edinburgh in collaboration with SRUC and an industrial partner, NCIMB Ltd. It provides an opportunity to cross disciplines between clinical and environmental microbiology, taking a true One Health approach. Partnership with NCIMB Ltd provides access to one of the UK biobanking companies, showcasing the application of microbiology in commercial settings.

Funding Notes

Apply Now

EASTBIO Webpage (to download the documents required for email application process, detailed below)

EASTBIO Application
Equality, Diversity and Inclusion (EDI) survey
Reference Forms can be downloaded via link above

Please send your completed EASTBIO Application Form and EDI survey along with a copy of your academic transcripts to CIR.Postgraduate@ed.ac.uk before the deadline.

You should also ensure that two references have been sent to CIR.Postgraduate@ed.ac.uk by the deadline using the EASTBIO Reference Form.

Unfortunately due to workload constraints, we cannot consider incomplete applications.

This article was published on 2024-09-10