Fully funded 4 Year PhD studentships in Biomedical Sciences

Project location 

TBC

Contact

Tijana.mitic@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Jian Liu (Zhejiang University, ZJE) 

Dr Andrea Caporali (Edinburgh INCR) A.Caporali@ed.ac.uk 

Prof Tomasz Guzik (Edinburgh, INCR) tguzik@ed.ac.uk

Project description

Aortic ascending aneurysm (AscAA) is a life-threatening cardiovascular condition across the world, marked by silent dilation of the aorta, potentially leading to fatal dissection or rupture. The exact mechanisms behind AscAA formation remains unclear, although epigenetic regulation are known to be implicated (1).

Currently, identification of biomarkers and effective pharmacological treatment is a common global effort to significantly impact patients’ care. Recent evidence suggests that the non-coding-RNA (lncRNA and microRNAs) are involved in developing many cardiovascular diseases. Data from Caporali lab shows direct protection from apoptosis in vascular cells with microRNA-26b (miR-26b) depletion during injury (2), with miR-26b expression inversely correlating with medial microcalcification, a hallmark of aortopathies. 
More, data from Mitic lab demonstrates lncRNA-MEG3 involvement in directing the chromatin conformational changes over microRNA promoters and nearby enhancer regions in the aortic cells/tissue (3). These specific genomic elements overlap regions with genetic variants with causal mutations for aortic aneurysm (3-4).

Together, we wish to unravel the epigenetic layers of regulation of these genomic elements in aortic aneurysm. We propose that, by analysing target genes and the epigenetic modifiers at relevant enhancers/promoters, it is possible to identify the treatments and protect aortopathy.

The main hypothesis for this work is that loss of two identified regulatory enhancers promotes dysregulation of signalling in vascular cells, leading to AscAA initiation and progression.

Approaches used in project

This project will integrate computational, genomic and molecular approaches to investigate miRNA-26b regulatory mechanisms in AscAA (1). Circulating miRNA-26b levels will be assessed for their potential as disease biomarkers. 

Using multi-omics analyses (e.g. Hi-C, RNA-seq, ChIP-seq, ATAC-seq) we will explore upstream regulation of key enhancer elements, supported by an established ChIP-seq analysis framework (4) and initial data processing by the Beijing Genomics Institute. Epigenetic regulators with therapeutic relevance will be prioritised using existing patient samples and animal models of AscAA (1). 

The project will also support comprehensive research training and professional development of the PhD candidate through TNE and HEA activities.

Relevant references for project background

[1] Luna Buitrago D, Mameli E, Jover E, Mellis D, Nosalslki R, Charlton L, Bauza Sanso R, Dunn-Davies H, MacAskill M, Tavares A, Fletcher A, López-Andrés N, Hadoke P,. Wagner BD, Robinson ML, Baker AH, Newby D, Mitić T, Caporali A. (2025) The loss of microRNA-26b promotes aortic calcification through the regulation of cell-specific target genes. Cardiovasc Res, 2025 Sept, 121(11):1778–1792. 

[2] Debono S, Nash J, Fletcher AJ, Syed M, van Beek EJR, Williams MC, Falah O, Tambyraja A, Dweck MR, Newby DE, Forsythe RO. Aortic sodium [18F]fluoride uptake following endovascular aneurysm repair. Heart. 2023 Oct 26;109(22):1677-1682;     

[3]  Martello A, Mellis D, Meloni M, Howarth A, Ebner D, Caporali A, Al Haj Zen A. Phenotypic miRNA Screen Identifies miR-26b to Promote the Growth and Survival of Endothelial Cells. Mol Ther Nucleic Acids. 2018 Dec 7;13:29-43. doi: 10.1016/j.omtn.2018.08.006  

[4] Dunn-Davies H, Dudnakova T, Nogara  A, Rodor J, Thomas AC, Parish E, Gautier P, Meynert A, Ulitsky I, Madeddu P, Caporali A, Baker A, Tollervey D, Mitić T. Control of endothelial cell function and arteriogenesis by MEG3:EZH2 epigenetic regulation of integrin expression. Mol Ther - Nucleic Acids. 2024 Jun; 35(2):102173.    

[5]  Monteiro JP, Rodor J, Caudrillier A, Scanlon JP, Spiroski AM, Dudnakova T, Pfluger-Muller B, Shmakova A, von Kriegsheim A, Deng L, Taylor RS, Wilson-Kanamori JR, Chen SH, Stewart K, Thomson A, Mitić T, McClure JD, Iynikkel J, Hadoke PWF, Denby L, Bradshaw AC, Caruso P, Morrell NW, Kovacic JC, Ulitsky I, Henderson NC, Caporali A, Leisegang MS, Brandes RP, Baker AH. Mir503hg loss promotes endothelial-to-mesenchymal transition in vascular disease. Circ Res. 2021;128:1173-1190.

Project location 

Hugh Robson Building, George Square. 

Contact

q.zhou@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Wenwen Huang, ZJE. Email: Wenwenhuang@intl.zju.edu.cn 

Prof Timm Krueger, UoE. Email: Timm.krueger@ed.ac.uk 

Project description

The rupture of aneurysms developing in the brain are the leading cause of subarachnoid haemorrhage, a main type of stroke (about 1.3 million people live with stroke in the UK and the associated deaths amount to ca. 38,000 each year). However, there are still unmet needs for new therapies to treat risky aneurysms while reducing the use of exogenous implants (e.g. metallic coils or flow-diverting stents), which may cause post-operative formation of blood clots and ischaemic stroke especially in hypertensive patients. Recently, novel micro/nanorobots (MNRs) have achieved active delivery of embolic agents to aneurysms for precise robotic embolisation [1]. 

Notwithstanding, more demanding pre-clinical developments in both anatomically and physiologically realistic environments mimicking the human vasculature are necessary preceding clinical trials (e.g. using animals). One critical question is then how physical/animal experiments of MNRs in surrogate models can seed and safeguard ethical trials in humans.

Whereas conventional clinical trials require stringent regulations and time-consuming phases, the maturing in silico technologies, empowered by supercomputing and machine learning, provide a timely and efficient alternative to assess the emerging MNR therapies through digital twins, which would significantly accelerate their clinical translation and regulatory approval towards a leap. 

This project aims to unravel the effect of cellular interactions and oscillatory haemodynamics on the controlled motion of MNRs in a realistic vascular environment through computational modelling and simulations, in combination with supplementary experimental validation. Additionally, the efficiency of solute transport for drug-delivering (e.g. thrombolytics) MNRs under physiological blood flow conditions will be investigated. 

Approaches used in project

i) Model development: Integration of numerical modules for simulating MNRs in biofluids on the basis of a reported flow solver [2]

ii)Model validation: 1) MNR optimisation with the developed model for different vascular geometries and physiological flow conditions; 2) Validation against literature for uncertainty quantification.  

iii) Model consolidation: 1) Extension of the simulation toolkit by integrating data assimilation and parameter inference; 2) In silico trials of animal-tested MNRs reported in literature.  

iv) Device innovation and MNR fabrication: 1) Setup innovation subject to functional extension [3]; 2) MNR fabrication for experiments in bio-fabricated phantoms [4,5].

Relevant references for project background

[1] J Wang, Q Zhou, Q Dong, J Shen, J Hao, D Li, T Xu, X Cai, W Bai, T Ying, Y Li, L Zhang, Y Zhu, L Wang, J Wu, Y Zheng. Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy. Small 20(36): 2400408, 2024. (featured as Editor’s Choice)

[2] Q Zhou, T Perovic, I Fechner, LT Edgar, PR Hoskins, H Gerhardt, T Krueger, and MO Bernabeu. Association between erythrocyte dynamics and vessel remodelling in developmental vascular networks. Journal of The Royal Society Interface, 18(179):20210113, 2021. 

[3] Qi Zhou, T Petit, H Choi, BJ Nelson, and L Zhang. Dumbbell Fluidic Tweezers for Dynamical Trapping and Selective Transport of Microobjects. Advanced Functional Materials, 27(1):1604571, 2017. (featured as journal front cover) 

[4] H Zhao, B Yu, D Yu, T Ji, K Nie, J Tian, X Shen, K Zhang, J Ou, X Yang, D Xiao, Q Zhou, W Huang*. Electrochemical‐Genetic Programming of Protein‐Based Magnetic Soft Robots for Active Drug Delivery. Advanced Science, 2503404 (featured as journal inside front cover) 

[5] D Zhong, K Jin, R Wang, B Chen, J Zhang, C Ren, X Chen, J Lu, M Zhou. Microalgae-Based Hydrogel for Inflammatory Bowel Disease and Its Associated Anxiety and Depression, Advanced Materials, 36(24): 202312275, 2024.

Project location 

Hugh Robson Building, George Square. 

Contact

Richard.Sloan@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Matt Brook, Centre for Cardiovascular Science. Email: Matt.Brook@ed.ac.uk

Dr Wanlu Liu, ZJE. Email: Wanluliu@intl.zju.edu.cn

Project description

The aim of this project is to understand how genomic endogenous retroelements influence bats’ unique immune responses and thus their role as viral reservoirs. Bats have been the source of viral spillovers such as SARS-CoV-2, Marburg virus, and Nipah virus. Their ability to cope with the metabolic stress of powered flight is thought to necessitate an anti-inflammatory immune state.

Endogenous retroelements propagate themselves throughout genomes, causing genetic disruption and inflammatory responses to their nucleic acids. These inflammatory responses can shape innate and adaptive immunity, impacting areas like lymphocyte development, senescence, and B/T cell function. Generally, endogenous retroelements are then suppressed by host epigenetic and post-transcriptional mechanisms.

Our analysis of mammalian genomes shows that genes coding for proteins that regulate retroelement expression (e.g. HUSH complex) are under positive selection, suggesting the evolution of altered function in bats. Potentially, the strong selection pressure to curtail inflammation in bats leads to selection for endogenous retroelement-regulatory gene products to be more suppressive. Our preliminary data also shows altered transposon integration patterns in some bat species.

We will conduct evolutionary genetic analysis with newly sequenced bat genomes to further identify bat retroelement regulators with altered functions. Using RNA sequencing and molecular biology methods, we will then examine effects on epigenetic marks, retroelement transcription, and RNA metabolism. Next, we will explore how variations in retroelement expression affects antiviral and inflammatory responses in bat cell lines and iPSC-derived immune cells. 

Overall, this research will reveal how differential regulation of endogenous retroelements underpins bats’ status as key viral reservoirs.

Approaches used in project

This project will use a mix of computational, molecular, and immunological approaches. Genes of interest will be identified through positive selection analysis of mammalian genomes. Panels of cloned endogenous retroelement regulators will be screened for effects on human and bat endogenous retroelements. Both qPCR and RNA sequencing will be used to determine levels of endogenous retroelement RNA in knockout bat cell lines. Alternative qPCR or sequencing technologies to define changes in transcription or epigenetic modifications may also be used. Innate immune responses will be measured in cell lines as well as bat iPSC derived immune cells.

Relevant references for project background

1. Bat genomes illuminate adaptations to viral tolerance and disease resistance Morales A et al. Nature. (2025) 638, 449–458

2. Lessons from the host defences of bats, a unique viral reservoir. Trent-Irving A et al. Nature. (2021). 589, 363–370

 3. Alternative splicing expands the antiviral IFITM repertoire in Chinese horseshoe bats. Mak N, Zhang D, Li C, Rahman K, Datta SAK, Taylor J, Liu J, Shi Z, Temperton N, Trent-Irving A*, Compton AA*, Sloan RD*. PLoS Pathogens. (2024) 20,12: e1012763.

 4. MORC1 represses transposable elements in the mouse male germline. Pastor WA, Stroud H, Nee K, Liu W, Pezic D, Manakov S, Lee SA, Moissiard G, Zamudio N, Bourc’his D, Aravin AA, Clark AT, Jacobsen SE. Nature Communications. (2014). 5:5795.

 5. Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation. Brook M, Tomlinson GH, Miles K, Smith RWP, Rossi AG, Hiemstra PS, van 't Wout EFA, Dean JLE, Gray NK, Lu W, Gray M. Proceedings of the National Academy of Sciences. (2016). 113(16):4350-4355.

Project location 

TBC

Contact

Robert.Young@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Chaochen Wang, ZJE. Email: chaochenwang@intl.zju.edu.cn

Project description

Variation across species, populations and individuals is thought to arise less from changes to protein-coding genes than from differences in how these genes are regulated. This regulation is often mediated through promoters and enhancers which are noncoding loci that frequently harbour genetic variants responsible for medical phenotypes and disease risk.

Pervasive creation and destruction of promoters and enhancers across evolution is increasingly recognised. Our recent work shows that, surprisingly, those loci which have been created along the human lineage are more likely to regulate molecular phenotypes than their conserved counterparts. These observations contrast with the clear utility and importance of evolutionary conservation in protein-coding genes, e.g. when studying disease models in non-human species such as mouse.

This project will attempt to resolve this conflict by exploring the importance of evolutionary conservation and volatility in gene expression and regulation within a biomedically-relevant context, namely breast cancer. While most your time will be spent in Edinburgh, you will have the opportunity to spend time performing research at our international campus at Haining, China.

The project has three elements:
1)    Bioinformatic characterisation of differential gene expression data across 21 well-annotated breast cancer-associated genes contained within the Cancer Gene Census which have been studied in both human and mouse systems and are publicly available from the ARCHS4 database.
2)    Molecular biology experiments to generate enhancer landscapes across human and mouse cell lines to directly compare with gene expression differences across species identified in stage 1.
3)    Differentially-regulated genes, promoters and enhancers will be subsequently investigated using bioinformatics analyses, e.g. evolutionary trajectory reconstruction and association with approved drug-gene interactions. 

Approaches used in project

Most computational work will be performed on the University of Edinburgh’s high-performance computing cluster Eddie. You will use a combination of various computational software (BEDTools, Bowtie, DESeq2) and statistical analyses (in the R programming language). 

An ideal candidate will have prior experience in computational and statistical biology, such as working in a Linux environment. Molecular biology (qPCR, Western blots, etc) and multi-omics (ATAC-seq, CUT&Tag-seq) will be performed at ZJE alongside researchers in the Wang lab who routinely use these technologies.

Relevant references for project background

1. Jubb AW, Young RS, Hume DA, Bickmore WA. Enhancer Turnover Is Associated with a Divergent Transcriptional Response to Glucocorticoid in Mouse and Human Macrophages. Journal of Immunology 196(2), 813-822 (2016). https://doi.org/10.4049/jimmunol.1502009  

2. Young RS, Talmane L, Marion de Procé S, Taylor MS. The contribution of evolutionarily volatile promoters to molecular phenotypes and human trait variation. Genome Biology 23(1), 89 (2022). https://doi.org/10.1186/s13059-022-02634-w  

3. Wong ES, Thybert D, Schmitt BM, Stefflova K, et al. Decoupling of evolutionary changes in transcription factor binding and gene expression in mammals. Genome Research 25(2), 167-178 (2015). https://doi.org/10.1101/gr.177840.114  

4. Li M, Han Y, Wang C, Kang W, et al. Dissecting super-enhancer driven transcriptional dependencies reveals novel therapeutic strategies and targets for group 3 subtype medulloblastoma. Journal of Experimental & Clinical Cancer Research 44(1), 311 (2022). https://doi.org/10.1186/s13046-022-02506-y 

5. Lachmann A, Torre D, Keenan AB, et al. Massive mining of publicly available RNA-seq data from human and mouse. Nature Communications 9, 1366 (2018). https://doi.org/10.1038/s41467-018-03751-6  

Project location 

Hugh Robson Building, George Square.

Contact

David.Hay@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Prof Paul Le Tissier (INCR). Email: Paul.LeTissier@ed.ac.uk

Project description

The anterior pituitary is a highly vascularised organ at the base of the brain which secretes hormones which are essential for regulation of metabolism, reproduction, stress and growth. 

The organisation of cells and their relationship to the capillary network within the gland is important in both exposure of cells to regulatory factors and delivery of secreted hormones to target organs [1]. Induced pluripotent and resident pituitary stem cells are able to differentiate and maintain gland function [2] and recent studies have demonstrated their use to model in vitro normal pituitary development and pathology [3] but this has not included the vasculature. 

This project will adapt our novel approaches for 3D culture in microwells [4] to differentiate pituitary stem and endothelial cells and image the dynamics of their interaction. High-throughput screening of candidate factors altering the interaction of the endocrine cells with the vasculature will then provide an understanding of its normal regulation. This may provide therapeutic targets for modifying pituitary output in treatment of endocrine deficiencies and pituitary tumours. 

Approaches used in project

Isolation and culture of pituitary stem cells; culture and differentiation of induced pluripotent stem cells; live imaging; primary cell transduction (potentially including CRISPR-Cas gene editing); high throughput screening. 

Relevant references for project background

[1] Le Tissier P et al., Nat Rev Endocrinol. 13(5):257-267. doi: 10.1038/nrendo.2016.193.  

[2] Andoniadou CL et al., Cell Stem Cell. 13(4):433-45. doi: 10.1016/j.stem.2013.07.004.  

[3] Mac TT et al ., Elife.12:RP90875. doi: 10.7554/eLife.90875.

[4] Kasarinaite A et al ., Stem Cell Res Ther. 16(1):130. doi: 10.1186/s13287-025-04238-0. 

Project location

TBC

Contact

Mikael.Bjorklund@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Prof David Hay Email: David.Hay@ed.ac.uk

Project description

Precise coordination between cell size and metabolic activity is essential for normal cell function, with mitochondria playing a key role (Meliala et al, PNAS 2025; Caldez et al, Dev Cell 2018). Building on our most recent work (Meliala et al, PNAS 2025), this project aims to establish that manipulating NAD+/NADH redox balance between mitochondria and cytoplasm can simultaneously optimize cell size and metabolic function. 

By focusing on improving mitochondrial function in defined cell culture systems such as human pluripotent stem cells, we hypothesize that an engineered liver tissue derived from such cells with improved mitochondrial function better recapitulates metabolic function of mature hepatocytes. 

We further hypothesize that lipid accumulation occurs as a compensatory mechanism to mitigate redox imbalance, and therefore the optimized tissue engineering platform will be applied to study early steatosis. 

This work addresses critical questions in cell biology as well as aims to remove barriers in tissue engineering (metabolic immaturity) and metabolic dysfunction-associated steatotic liver disease (MASLD) research (lack of physiological human models), with potential for drug screening and future development of tissue implants for a disease affecting ~25% of the global population. 

More broadly, these findings will advance fundamental understanding of how cells coordinate size, mitochondrial function, and metabolism with potential applications to other areas of regenerative medicine.

Approaches used in project

2D and 3D tissue culture, fluorescence microscopy and holotomography,  metabolic assays, omics

Relevant references for project background

Caldez et al, Dev Cell 2018 (PMID: 30344111); Meliala et al, PNAS 2025 (PMID: 40478883)

Project location

TBC

Contact

Gedi.Luksys@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Robin Hill, Edinburgh Informatics. Email: r.l.hill@ed.ac.uk

Project description

Research in decision making has been an interdisciplinary success story; however, recently the focus has shifted from basic experiments to ecological settings, including online platforms. Information collected there, also called digital phenotyping, is more complex yet can provide insights beyond basic mechanisms of decision making to help answer questions of enormous relevance, such as what are societal implications of our interaction with news media or when gaming can lead to addiction and other mental health problems. 

In this project we focus on our developed news aggregator platform, mynewsscan.eu, to investigate neurocognitive factors that shape our interaction with news media and how it can be linked to mental traits and states in health and disease. We also developed the Paintings/Quotes experiment to investigate the role of schemas and modulatory factors (e.g. risk, novelty) in decision making as well as computational models that use error-based learning, motivation, and drift-diffusion model components. 

The PhD will build upon findings from both experiments to employ MyNewsScan as a community-driven platform for large-scale collection of data, with some Edinburgh-based participants recruited for biometric (eye-tracking, heart rate, emotional expressions) and/or neuroimaging (fMRI/EEG) studies. 

In addition to our collaboration with HealthyGaming company, that aims to understand the gaming disorder, our core aim is to understand how biometric and neuroimaging markers of decision making relate to behavioural metrics and questionnaire-based data (including factors like stress, motivation and sleep), and whether easily collectable digital markers can predict neuropsychiatric conditions that require costly clinical assessments.

Approaches used in project

Depending on student’s expertise and interests, the project will include (but is not limited to) a number of the following methods: behavioural/cognitive experiments in humans, both online and in laboratory, collection and analysis of biometrics and/or neuroimaging data, management and further development of MyNewsScan platform and its user community, computational modelling of learning and decision making (e.g. reinforcement learning, drift diffusion, motivation models) and their parameter estimation, advanced statistics (e.g. mixed models), machine learning and natural language processing, questionnaire-based and clinical characterisation of neuropsychiatric disorders, investigation of mental health and decision making data from gaming platforms.

Relevant references for project background

Vosoughi et al., “The spread of true and false news online”, Science 2018; 

Huckvale et al., “Toward clinical digital phenotyping: a timely opportunity to consider purpose, quality, and safety”, npj Digital Medicine 2019; 

Strasser et al., “Glutamine-to-glutamate ratio in the nucleus accumbens predicts effort-based motivated performance in humans”, Neuropsychopharmacology 2020; 

Shinn et al., “A flexible framework for simulating and fitting generalized drift-diffusion models”, eLife 2020; 

Luksys et al., “Stress, genotype and norepinephrine in the prediction of mouse behavior using reinforcement learning”, Nature Neuroscience 2009

Project location

TBC

Contact

Duncan.Macgregor@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Prof Mike Ludwig (INCR). Email: Mike.Ludwig@ed.ac.uk

Project description

Mechanisms based mainly in the brain’s hypothalamus act to regulate thirst, water loss, and salt excretion, in order to maintain the homeostasis of osmotic pressure (the balance between salt and water). Water is regularly lost through respiration and perspiration. Salt is gained through feeding, and lost through perspiration. The hormone vasopressin, secreted by hypothalamic neurons, acts at the kidneys to regulate water loss in response to signals that encode osmotic pressure. Oxytocin similarly acts to regulate salt excretion, and other signals including aldosterone act to regulate thirst. 

To understand how all these elements interact we want to build an initially simple physiological model of this system starting from very basic assumptions and gradually building complexity, working towards integrating the new physiological model with our existing modelling of the hypothalamic neural mechanisms.

The initial focus of this project will be on modelling the process of water consumption, including drinking, absorption, loss through the kidneys, and the transfer of water between extracellular and intracellular compartments. As well as the modelling this will require gathering and analysing, from published sources and our own experimental archives, quantitative experimental data with which to base the mechanisms and test the behaviour of the model.

The core technique will be differential equation based system modelling, implemented in our HypoMod software, using coding in either C++ or Python. The first major objective will be to assemble sufficient components to simulate the basic vasopressin and thirst control of water intake and loss, able to maintain osmotic homeostasis under a realistic simulation of periodic drinking events.  

Approaches used in project

Computational modelling, systems approach, data analysis, literature review

Relevant references for project background

Ramsay DJ. The importance of thirst in maintenance of fluid balance. Baillieres Clin Endocrinol Metab. 1989 Aug;3(2):371-91. doi: 10.1016/s0950-351x(89)80008-4.  

Zimmerman CA, Leib DE, Knight ZA. Neural circuits underlying thirst and fluid homeostasis. Nat Rev Neurosci. 2017 Aug;18(8):459-469. doi: 10.1038/nrn.2017.71.   

Verbalis JG. Disorders of body water homeostasis. Best Pract Res Clin Endocrinol Metab. 2003 Dec;17(4):471-503. doi: 10.1016/s1521-690x(03)00049-6.

Project location

Hugh Robson Building, George Square. 

Contact

John.Menzies@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Richard Fitzpatrick EMS/ZJE. Email: Rfitzpa2@ed.ac.uk. 

Prof Shuang Qiu ZJU/ZJE. Email: Qiushly@zju.edu.cn

Project description

How do biomedical sciences students feel about the animals used in research? How do we help them develop an ethical and scientifically productive relationship with the animals they use and how does this affect the science they do? We use animal models because their physiology is similar enough to ours to simulate mental and physical health conditions. Thus, a tension may form, with animals considered similar enough to us to afford translational work, but sufficiently dissimilar to permit their (non-consensual) use in research. This tension might manifest as a downplaying of the experiences of animals, particularly lab animals such as rats and mice, and as a dismissal of animals’ sentience and individuality as anthropomorphism.

How can we explore these challenging and contentious ideas? One way is via play. A video game may foster common ground in which these complex ethical situations can be confronted in ways that are contextually authentic, that offer ethically meaningful choices, and that drive genuine introspection. The PhD will continue the development of a digital game that encourages players to explore beliefs and values towards laboratory animals. 

The aims are (1) to create a game which acts as an open, compassionate, supportive and scientifically robust multi-audience setting for raising ethical and scientific questions, and (2) use the game as a tool to explore ethical stances in biomedical students, researchers and aligned groups. 

Approaches used in project

Game development will involve working with one of the common game engines (e.g., Unity, Unreal Engine), based on prior experience and skillset, as well as our existing protypes. A modular, scenario-based approach will be used to generate authentic laboratory-based gameplay. 

Appropriate systems for collection of game telemetry within ethical frameworks will be designed, applying inclusive and accessible UX design as much as feasible. Latterly, the project will involve using an iterative mixed methods approach, using focus groups, interviews and questionnaires to gather information on attitudes and beliefs related to the use of lab animals.

Relevant references for project background

Fitzpatrick R, Romanò N, Menzies J. Exploring Compassion towards Laboratory Animals in UK- and China-Based Undergraduate Biomedical Sciences Students. Animals. 2023;13(22):3584. doi:10.3390/ani13223584; 

Vezirian K, Bègue L, Bastian B. Mindless furry test-tubes: Categorizing animals as lab-subjects leads to their mind denial. Journal of Experimental Social Psychology. 2024;114:104629. doi:10.1016/j.jesp.2024.104629; 

Despret V, Buchanan B. What Would Animals Say If We Asked the Right Questions? University of Minnesota Press; 2016. 

Project location

TBC

Contact

John.Menzies@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Celine Caquineau (BMTO). Email: Celine.Caquineau@ed.ac.uk

Project description

The University of Edinburgh-Zhejiang University Joint Institute (ZJE) is a transnational higher education (TNE) partnership based in Haining, China. ZJE hosts ~600 undergraduate students on two dual-award, research-rich programmes in biomedicine. These students are taught in-person by academic staff based in either China or the UK. 

To date, research on Teaching and Student Learning (T&L) in China-UK TNE contexts is sparse, but ZJE provides a unique, supportive and accessible setting for an educational research project on staff and student experiences in UK-China internationalised learning. We will explore diverse themes such as teaching staff and student’s practices, motivations, agency, identity and senses of mattering and belonging, and focus on key factors that lead to high-quality learning and teaching experiences. 

We anticipate this distinctive project will have wide-spread influence in the field of TNE research by providing key foundational evidence to better understand T&L practices at ZJE and across the many other UK-China TNE partnerships. Being exploratory in nature, we believe this project provides a unique, pioneering and potentially transformative opportunity for a PhD researcher to develop a strategic direction for research into TNE. 

The supervisory team has extensive experience in T&L in both UK and China. Both supervisors have Advance HE accreditations and have supported numerous PhD researchers in the development of their teaching practices. 

Approaches used in project

First, the student will carry out a systematic review of TNE research to identify knowledge gaps. Informed by the review, the student will then identify and agree the focus of their investigation. The project will encompass mixed quantitative and qualitative methods to directly address specific research questions. The project will use different ways of generating and analysing data to provide an in-depth and inclusive understanding of the ZJE community, and thus to identify potential challenges and opportunities in enhancing student and staff experiences. 

Relevant references for project background

www.ed.ac.uk/biomedical-sciences/connections-outreach/international-activities/zje-institute

www.britishcouncil.cn/en/programmes/education/higher/TNE

Project location

TBC

Contact

Matt.Brook@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Elizabeth Haythorne (INCR). Email: Ehaythor@ed.ac.uk

Project description

Type 2 diabetes (T2D) afflicts >4.5 million people worldwide. It is characterised by chronic hyperglycaemia due to inadequate insulin secretion from pancreatic β-cells [1]. Additionally, chronic hyperglycaemia also gradually damages β-cells so that they release even less insulin over time, leading to further hyperglycaemia and more β-cell damage [2,3]. However, the molecular mechanism(s) by which chronic hyperglycaemia impairs insulin secretion, remains unclear.

 RNA-binding proteins (RBPs) are crucial regulators of insulin secretion, playing a key role in the post-transcriptional control of gene expression in pancreatic β-cells. They influence various aspects of RNA metabolism, including mRNA splicing, translation, and stability, all of which impact insulin production and secretion [4]. Given their central role in β-cell function, a better understanding of the connection between RBPs and insulin secretion is essential. It is also important to understand how this process changes during chronic hyperglycaemia (as occurs during T2D). This knowledge is crucial for comprehending the molecular mechanisms that regulate β-cell function and may also provide insights into the pathophysiology of T2D.

Thus, this project aims to investigate how regulation of RBPs underpins normal β-cell glucose responsiveness and how this is dysregulated during glucotoxicity, as experienced during chronic hyperglycaemia in vivo, resulting in impaired insulin production. This will be done using cutting-edge molecular and cellular methods in vitro β-cell models and in vivo T2D models that recapitulate physiological and pathophysiological glucose/insulin homeostasis.

Approaches used in project

i) in vitro, in cellulo, and in vivo models of T2D; 

ii) RNA-binding protein capture; 

iii) proteomics/transcriptomics; 

iv) bioinformatics/human genetics

Relevant references for project background

[1] U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group. Diabetes. (1995). 44:1249-58.   

[2] Haythorne E, Lloyd M, et al. Altered glycolysis triggers impaired mitochondrial metabolism and mTORC1 activation in diabetic β-cells. Nat Commun. (2022). 13:6754.   

[3] Haythorne E, Rohm M, et al. Diabetes causes marked inhibition of mitochondrial metabolism in pancreatic β-cells. Nat Commun. (2019). 10:2474.   

[4] Quezada E, Knoch KP, et al. Aldolase-regulated G3BP1/2+ condensates control insulin mRNA storage in beta cells. EMBO J. (2025). 44(13):3669-3696. 

[5] Gebauer F, Schwarzl T, Valcárcel J, Hentze MW. RNA-binding proteins in human genetic disease. Nat Rev Genet (2021). 22(3):185-198

Project location

TBC

Contact

Matt.Brook@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Di Chen, ZJE Institute. Email: DiChen@intl.zju.edu.cn

Project description

Poly(A)-binding protein C1 (PABPC1) is an RNA-binding protein that binds to mRNA poly(A) tails to coordinate mRNA translation and decay. Dysregulated PABPC1 level and/or function are emerging factors in human disease, but particularly in multiple cancer types. Greater understanding of the functions and regulation of PABPC1 is therefore urgently required to reveal points for potential therapeutic intervention.

Much is known about how PABPC1 forms protein complexes with key partners to regulate aspects of mRNA metabolism (e.g. eIF4G interaction in translation stimulation, eRF3 interaction in translation termination, TNRC6A interaction in nonsense-mediated decay) but PABPC1 has >20 confirmed interaction partners, many with disparate or antagonistic functions, and how these interactions are coordinated is poorly understood. We, and others, previously identified many post-translational modifications (PTMs) on PABPC1, including phosphorylation (S/T/Y), acetylation (K), methylation (K/R/D/E) and more. We have demonstrated that PABPC1 PTM status is dramatically altered in certain cellular contexts, e.g. cell cycle stages, and have characterised one PTM that alters PABPC1 affinity for the translation termination factor eRF3a. However, it is otherwise unclear which PTMs regulate specific PABPC1 interactions to modulate the utilisation and fate of PABPC1-associated mRNAs. 

We will analyse previously unstudied PABPC1 PTMs to identify their effects on protein and RNA binding, regulatory effects on target mRNAs, and both the upstream signalling pathways and effectors required for the PTM and the downstream gene expression pathways affected by the PTM. In doing so, we will reveal novel PABPC1 PTM-dependent gene regulatory networks of potential relevance to human health.

Approaches used in project

1) Cell culture models/gene editing/reporter gene systems 

2) proteomics and transcriptomics 

3) human genetics/genomics 

4) structural biology

Relevant references for project background

1) Farouk, I.A., Low, Z.Y., et al. (2024). PABPC1: A Novel Emerging Target for Cancer Prognostics and Anti-cancer Therapeutics. In: Sobti, R.C., Sugimura, H., Sobti, A. (eds) Molecular Biomarkers for Cancer Diagnosis and Therapy. 

2) Sun, C., Xu, X., Chen, Z. et al. Selective translational control by PABPC1 phase separation regulates blast crisis and therapy resistance in chronic myeloid leukaemia. Nat Cell Biol 27, 683–695 (2025). 

3) Mangkalaphiban, K, Ganesan, R, and Jacobson, A. (2023) Direct and indirect consequences of PAB1 deletion in the regulation of translation initiation, translation termination, and mRNA decay. BioRxiv doi: 10.1101/2023.05.31.543082. 

4) Brook M, McCracken L, et al. (2012) The multifunctional poly(A)-binding protein (PABP) 1 is subject to extensive dynamic post-translational modification, which molecular modelling suggests plays an important role in co-ordinating its activities. Biochem J. 441(3):803-12. 

5) Shan, P, Fan, G, et al. (2017) SIRT1 Functions as a Negative Regulator of Eukaryotic Poly(A)RNA Transport. Curr Biol. 27(15):2271-2284.

Project location

TBC

Contact

Matt.Brook@ed.ac.uk

Name, location and email of co-applicants (Supervisory Team)

Dr Rob Semple (INCR). Email: Rsemple@ed.ac.uk

Project description

Fully understanding the processes by which preadipocytes differentiate into mature adipocytes is crucial to our ability to identify pathways that can be manipulated to benefit human health; E.g., preventing either the acquisition of excess adiposity or the loss of adipose depots during ageing/disease. Mouse cell culture models, and limited studies utilising human adipocyte precursor systems, have been used to identify numerous pathways and effector molecules that function in adipogenesis. 

However, most studies focused on transcriptional regulation of gene expression, and it is now very clear that a significant proportion of adipogenic gene regulation is occurring at the post-transcriptional level (splicing, polyadenylation, translation, mRNA decay) but the majority of this regulation remains unstudied and the RNA-binding proteins (RBPs) that are required to coordinate it remain to be identified.

We are currently identifying the RBPs that coordinate gene expression during the full process of human adipogenesis (specification to mature adipocyte), quantifying their regulation, and simultaneously capturing target mRNAs. In collaboration with colleagues in Edinburgh and Copenhagen, we are leveraging RBPomics, transcriptomics, mass spectrometry, and human genetics to reveal new insights into adipogenic post-transcriptional gene regulatory networks with a view to gaining a new understanding of this cell type/tissue that is so crucial to human health.

This project will delineate the target mRNAs and functional regulation conferred by prioritised RBPs, will interrogate the molecular mechanisms therein, and will reveal the novel upstream control pathways and the downstream gene expression outcomes that are critical to identify potential points for therapeutic intervention in adipocyte/adipose function.

Approaches used in project

i) Human Mesenchymal stem cell culture and adipocyte differentiation models; 

ii) RNA-binding protein capture; 

iii) proteomics/transcriptomics; 

iv) bioinformatics/human genetics

Relevant references for project background

1) Koletsou, E., Huppertz, I. RNA-binding proteins as versatile metabolic regulators. npj Metab Health Dis 3, 1 (2025). 

2) Conn, CS. et al. (2021) The major cap-binding protein eIF4E regulates lipid homeostasis and diet-induced obesity. Nat Metab. 3(2):244-257. 

3) Zhang, P.;Wu,W.; et al. RNA-Binding Proteins in the Regulation of Adipogenesis and Adipose Function. Cells 2022, 11, 2357. 

4) Siang DTC, Lim YC, et al. The RNA-binding protein HuR is a negative regulator in adipogenesis. Nat Commun. 2020 Jan 10;11(1):213. 

5) Yan, S., Zhou, X., Wu, C. et al. Adipocyte YTH N(6)-methyladenosine RNA-binding protein 1 protects against obesity by promoting white adipose tissue beiging in male mice. Nat Commun 14, 1379 (2023).