Fully funded 4 Year PhD studentships in Biomedical Sciences

Applications are invited from outstanding students wishing to pursue a 4 Year PhD studentship in Biomedical Sciences from September 2025.

Based in the Edinburgh Medical School: Biomedical Sciences, University of Edinburgh you will have the opportunity to work with leading research groups while also developing your skills in transnational education. The studentships are fully funded for 4 Years including full fees (home or overseas), UKRI-level stipend and generous research costs. 

Alongside their PhD project, students will be supported in the development of their skills in TNE towards AFHEA accreditation. This will include short (typically 2 visits totalling 4-6 weeks per year) research and educational visits to our ZJE Joint Institute in China supported by their PhD supervisory team.

Applicants are required to discuss projects with prospective supervisors before submitting their application.

Candidates must meet University of Edinburgh PhD requirements including English language proficiency and acceptance is conditional on award of 2:1 degree classification (or similar) in a Biomedical related undergraduate Honours degree programme.

How to apply

Applications are now closed for 2025

List of PhD projects

Project location 

TBC

Contact

L.O'Hara@ed.ac.uk

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

Dr Nicola Romano, University of Edinburgh. Email: Nicola.Romano@ed.ac.uk

Project description

Visual learning aids are tools that helps people process, understand, and memorise information by presenting it visually. They can be a powerful tool for teaching biomedical science as they offer a way to help students better understand dynamic or complex systems, as well as the ability to ‘see the unseen’ eg the internal organs of the body or intracellular molecular signalling pathways. 

Examples of different types of visual aids include diagrams, simulations and videos, each has its own advantages and disadvantages. Visual aids may also be generated by students as part of their revision process and aid commitment of core concepts to long term memory. When used appropriately, visual aids may be especially useful for students learning biomedical science in their non-native language. However they can only be beneficial if students possess the appropriate visual literacy to understand them, and differing cultural interpretations of components such as colour and symbols must also be considered.

The student undertaking this project will investigate what makes a ‘good’ visual learning aid, and whether appropriate visual aids can enrich the learning of students with English as an additional language who are studying biomedical science and biomedical informatics at a UK-China Joint Educational Institute.     

Approaches used in project

Creation of visual learning aids such as diagrams, simulations and videos. Educational research methods such as surveys, focus groups and teaching interventions. 

Relevant references for project background

Kottmeyer, A. M., Van Meter, P. and Cameron, C. Diagram comprehension ability of college students in an introductory biology course. Advances in Physiology Education.  13 Mar 2020. https://doi.org/10.1152/advan.00146.2018.                     

Bobek, E., Tversky, B. Creating visual explanations improves learning. Cogn. Research 1, 27 (2016). https://doi.org/10.1186/s41235-016-0031-6. 

Miller KM and Yoon SA (2023) Teaching complexity in biology through agent-based simulations: the relationship between students’ knowledge of complex systems and metamodeling knowledge. Front. Educ. 8:1198307. doi: 10.3389/feduc.2023.1198307


Project location 

TBC

Contact

Tijana.mitic@ed.ac.uk

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

Jian Liu (Zhejiang University, ZJE) 

Andrea Caporali (Edinburgh QMRI) A.Caporali@ed.ac.uk

Pelin Sahlen (SciLife, Sweden)  

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

Project description

Aortic ascending aneurysm (AscAA) is a life-threatening cardiovascular condition across the world, marked by the silent dilation of the aorta, potentially leading to fatal dissection or rupture. The exact mechanisms behind AscAA formation are not well understood although in many cases the epigenetic regulation has been shown (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 the Caporali lab shows direct protection in vascular cells with microRNA-26b depletion from apoptosis during injury (2), with its expression inversely correlated with medial microcalcification, a hallmark of aortopathies. 

More, data from the Mitic lab demonstrates that specific lncRNA MEG3 directs the chromatin conformational changes over microRNA promoters and nearby enhancer regions in aortic cells/tissue (3). These specific genomic elements were shown to overlap the genetic variants with causal mutations for aortic aneurysm (3-4). Together, we wish to unravel the epigenetic layers of regulation of these elements in aortic aneurysm. We propose that, by analysing the target genes and the epigenetic modifiers on the 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

1. This project aims to identify the potential of circulating miR-26b as an AscAA biomarker. We will study the mechanisms underpinning miR-26b downregulation in AscAA, with the final aim of developing personalised therapy for AscAA patients.    

2. Additionally, we will study the upstream mechanism of regulation of identified enhancer elements, with the application of proteomics and genomics (e.g., HiC, RNA-Seq, ChIP-Seq, and ATAC-Seq). 

We are specifically interested in:  

1) The role of dysregulated chromatin architecture in AscAA; 

2) The function of epigenetic regulators in driving the development of AscAA, especially in human endothelial and smooth muscle cells, using CRISPR deletion. 

3) The identification of epigenetic drug targets for treatment of animal models of AscAA.  For this work the ChIP-seq bioinformatics pipeline has been published in reference (3). Briefly, Initial processing and alignment of sequenced ChIP-seq data will be performed by the Bejining Genomics Institute. Patients samples and animal models of AscAA will be used to validate epigenetic targets.

Relevant references for project background

[1] 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;    

[2]  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;    

[3] 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. Molecular Therapy Nucleic Acids. 2024; 35 (2), art. no. 102173.    

 [4]  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. Circulation Research. 2021;128:1173-1190.


Project location 

Hugh Robson Building, George Square.

Contact

P.J.Brunton@ed.ac.uk

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

Prof. Ruth Andrew (Centre for Cardiovascular Science) Email: Ruth.Andrew@ed.ac.uk

Project description

Maternal stress during pregnancy ‘programs’ long-lasting neuroendocrine and behavioural changes in the offspring1,2. Often this ‘programming’ is maladaptive and sex-specific. How the effects of maternal stress are transmitted from the mother to the fetuses is not known. Direct transfer of maternal glucocorticoids to the fetuses is often proposed to mediate the programming effects. However, we have shown that although corticosterone secretion is significantly greater in stressed dams compared with controls, there is no impact on corticosterone concentrations in the fetal circulation or brain3. In addition, maternal stress upregulates placental 11β-hydroxysteroid dehydrogenase-2 (the enzyme that inactivates glucocorticoids, limiting mother-to-fetus glucocorticoid transfer), suggesting this protective mechanism is intact3. These findings suggest a factor(s) other than glucocorticoids mediate fetal programming. 

The aim of this project is to investigate the factor(s) that signal maternal stress to the fetus. The placenta has several functions that make it a likely central player in mediating the effects of maternal stress4. As well as nutrient transport, the placenta also actively produces and secretes factors (e.g. steroids, monoamines, growth factors, cytokines) that can influence fetal brain development. We will perform a metabolomic screen of secretions from male and female placentae from stressed and non-stressed pregnancies. We will test whether identified candidate factors can mimic changes in gene expression observed in the prenatally stressed offspring brain. We will also investigate sex-dependent changes in placental gene expression induced by maternal stress, (in particular those involved in nutrient transport and allocation) and investigate whether these contribute to the programmed offspring phenotype. 

Approaches used in project

Behavioural observations will be used to monitor social stress induction in pregnant rats. Blood samples will be collected and immunoassays used to determine plasma hormone concentrations (primarily corticosterone). Mass spectrometry will be used for metabolomic profiling of placental secretions. Neuronal cell culture will be used to screen whether candidate placental factors can mimic changes in gene expression observed in the fetal/offspring brain.

Altered gene expression in the fetal brain, placentae neuronal cultures induced by maternal stress will be quantified by RNAscope/qPCR, while changes in protein expression will be assessed using immunocytochemistry/Western blotting.

Relevant references for project background

1.    Brunton, P. J. & Russell, J. A. 2010. Prenatal social stress in the rat programmes neuroendocrine and behavioural responses to stress in the adult offspring: Sex specific effects. J Neuroendocrinol, 22, 258-271. 10.1111/j.1365-2826.2010.01969.x

2.    Maccari, S., Krugers, H. J., Morley-Fletcher, S., Szyf, M. & Brunton, P. J. 2014. The consequences of early-life adversity: Neurobiological, behavioural and epigenetic adaptations. Journal of Neuroendocrinology, 26, 707-23. 10.1111/jne.12175

3.    Sze, Y., Fernandes, J., Kołodziejczyk, Z. M. & Brunton, P. J. 2022. Maternal glucocorticoids do not directly mediate the effects of maternal social stress on the fetus. J Endocrinol, 255, 143-158. 10.1530/JOE-22-0226

4.    Bronson, S. L. & Bale, T. L. 2016. The placenta as a mediator of stress effects on neurodevelopmental reprogramming. Neuropsychopharmacology, 41, 207-18. 10.1038/npp.2015.231


Project location

CDBS, 1 George Square.

Contact

Gedi.Luksys@ed.ac.uk

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

Robin Hill (Edinburgh Informatics/Edinburgh Futures Institute) Email: r.l.hill@ed.ac.uk

Project description

Research in decision making has been an interdisciplinary success story; however, only recently the focus has shifted from basic experiments to ecological settings, particularly 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 ultimate 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 collected 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

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

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

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

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

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


Project location

IRR, Bioquarter

Contact

Vasso.Makrantoni@ed.ac.uk

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

Dr Mikael Bjorklund (ZJE, China) Email: mikaelbj@intl.zju.edu.cn 

Prof Jeyaprakash Arulanandam (JP) (Institute of Cell Biology, Edinburgh) Email: jeyaprakash.arulanandam@ed.ac.uk

Prof David Dockrell (CIR-IRR, Edinburgh) Email: david.dockrell@ed.ac.uk

Project description

Fungal pathogens are a leading cause of human mortality worldwide, killing 1.5 million people every year. Candida albicans is the most common fungal pathogen in humans, responsible for life-threating infections, with devastating consequences in immunocompromised individuals. Under exposure to DNA damaging anti-fungal agents and cancer drugs, Candida morphology can switch from oval yeast to filamentous (pseudo)hyphae, which is required for full virulence. 

DNA damage repair relies on the cohesin complex, which keeps sister chromatids linked to provide a template for repair. Although homologs of most cohesin subunits have been identified in Candida, their function and contribution to DNA repair and morphology switching have not been studied. Using cohesin mutants, we have shown that cohesins play an important role in DNA damage-dependent filament formation.

In this project we aim to: (1) identify and define cohesin components and associated pathways that regulate morphological switching by Immunoprecipitation-Mass spectrometry (IP-MS), and biochemical/structural (cryo-EM) approaches to validate the cohesin interactome;(2) use CRISPR-Cas9 genome editing to generate new mutants of the cohesin complex and its functional interactome to assess sensitivity to genotoxins and associated morphological changes by viability/growth assays and live-cell imaging (microfluidics); (3) use human macrophages and 3D gut/intestinal organoids to reconstitute in vitro host-pathogen interactions, such to correlate cohesin-dependent morphology switching with virulence (live-cell imaging).

A better understanding of the Candida virulence following morphological switch will inform rational drug discovery and improve clinical treatment.

Approaches used in project

This PhD project is an interdisciplinary cross-institutional collaboration between the Institutes for Regeneration and Repair and of Cell Biology in Edinburgh, and the ZJE Institute in China. Although based in Edinburgh, the student will have the opportunity to get additional research training at ZJE in China. 

The student will learn: 

  • Structural/Biochemical approaches (in collaboration with JP lab); 
  • Sophisticated genetics (CRISPR-Cas9 genome editing, synthetic biology) and microscopy (in VM lab); 
  • Proteomics analysis for identification of novel interactors (in collaboration with MB lab); 
  • Tissue culture of ex-vivo host-pathogen infection models (macrophages, organoids) (with DD lab).

Relevant references for project background

1. Makrantoni V*., Hinshaw S*., Harrison SC., Marston AL. (2017). The Kinetochore Receptor for the Cohesin loading complex. Cell. 171, 72-84;

2. Makrantoni V. and Marston AL. (2018). Cohesin and chromosome segregation. Curr. Biol; 28, R688-R693;  

3. Parashara P. et al Jeyaprakash A.A. (2024). PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance. Science. 385, 1098-1104; 

4. Bjorklund, M. (2019). Cell size homeostasis: metabolic control of growth and cell division. Biochim. Biophys. Acta Mol. Cell Res. 1866, 409–417;  

5. Qing-Mei Shi., et al (2006). Critical Role of DNA Checkpoints in Mediating Genotoxic-Stress–induced Filamentous Growth in Candida albicans. Mol Biol of the Cell. 18, 815-826l.


Project location

IRR, Bioquarter

Contact

Vasso.Makrantoni@ed.ac.uk

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

Dr Mikael Bjorklund (ZJE, China) Email: Mikaelbj@intl.zju.edu.cn

Dr Edward Wallace (Institute for Cell Biology (ICB), Edinburgh), Email: Edward.wallace@ed.ac.uk

Prof David Dockrell (CIR-IRR, Edinburgh), Email: David.dockrell@ed.ac.uk

Project description

Candida albicans is ranked as the most critical priority pathogen by the World Health Organization. It is a member of the normal human mucosal microbiota, where as an opportunistic pathogen it can cause life-threatening systemic candidiasis in immunocompromised patients, with mortality rates exceeding 40%. Studies in clinical isolates revealed a remarkable genomic plasticity, commonly characterized by incorrect number of chromosomes (aneuploidy). This aneuploidy produces genetic diversity within the Candida population and selection will favour those cells best suited to growth in stressful conditions, such as antifungal drug treatment. With only four classes of antifungal drugs available, understanding the mechanisms of aneuploidy and identifying how Candida gains resistance to antifungal drugs are urgently needed.

A key molecular machine controlling aneuploidy is the cohesin complex, regulated by a druggable kinase-driven process. Evidence from our lab shows that defective and deregulated cohesin complex promotes aneuploidy when Candida experiences stress.

In this interdisciplinary project the student will:(1) engineer new cohesin mutants carrying synthetic fluorescently-labelled chromosomes by CRISPR-Cas9 genome editing, to measure aneuploidy following antifungal stress by live-cell imaging; (2) use omics-based approaches (ChIP-seq, RNA-seq, Proteomics) to identify key players regulating cohesin-derived aneuploidy;3) use human macrophages and 3D gut/intestinal organoids to reconstitute in vitro host-pathogen interaction to assess virulence.

The results of this research will inform discovery of new Candida-specific drug targets for antifungal therapies, an urgent need in the clinic.

Approaches used in project

This PhD project is an interdisciplinary cross-institutional collaboration between the Institutes for Regeneration and Repair and of Cell Biology in Edinburgh, and the ZJE Institute in China Although based in Edinburgh, the student will have the opportunity to get additional training and spend time performing research at ZJE in China. 

The student will learn sophisticated yeast genetics (CRISPR-Cas9 genome editing, synthetic biology); Live-cell imaging (microfluidics) to monitor single-cell aneuploidy; omics-based approaches (WGS, RNAseq, Proteomics) and data analysis (in collaboration with Bjorklund and Wallace labs); tissue culture of ex-vivo host-pathogen infection models (human macrophages, 3D gut/intestinal organoids) (in collaboration with Dockrell lab).

Relevant references for project background

1. Legrand M. et al., (2019). Candida albicans: An Emerging Yeast Model to Study Eukaryotic Genome Plasticity. Trends in Genetics. 35: 292-307;  

2. Makrantoni V*., Hinshaw S*., Harrison SC., Marston AL. (2017). The Kinetochore Receptor for the Cohesin loading complex. Cell. 171, 72-84;

3. Makrantoni V. and Marston AL. (2018). Cohesin and chromosome segregation. Curr. Biol. 28, R688-R693;

4. Sparapani S. and Bachewich K. (2019) Characterization of a novel separase-interacting protein and candidate new securin, Eip1p, in the fungal pathogen Candida albicans. Mol Biol of Cell. 30: 2469 – 2489. 


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] T Ji, H Shi, X Yang, H Li, DL Kaplan, J Yeo, W Huang, Bioinspired Genetic and Chemical Engineering of Protein Hydrogels for programable Multi-responsive Actuation, Advanced Healthcare Materials, 13(27): 2401562, 2024. 

[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 Aaron T Irving, ZJE. Email: Aaronirving@intl.zju.edu.cn

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, and Nipah viruses. 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 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.Reference-quality bat genomes illuminate adaptations to viral tolerance and disease resistance. Morales A,... Irving AT*, Hiller M*. 2024. Research Square. (2023). [Accepted at Nature October 2024]. 

2. Lessons from the host defences of bats, a unique viral reservoir. Irving AT 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, Irving AT*, Compton AA*, Sloan RD*. PLoS Pathogens. (2024) [Epub ahead of print]. 

4. Human reproduction is regulated by retrotransposons derived from ancient Hominidae-specific viral infections. Xiang X#, Tao Y#, DiRusso J, Hsu FM, Zhang J, Xue Z, Pontis J, Trono D, Liu W*, Clark AT*.  Nature Communications. (2022). 13(1):463 

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

Hugh Robson Building, George Square. 

Contact

John.Menzies@ed.ac.uk

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

Dr Celine Caquineau, BMTO. Email: C.caquineau@ed.ac.uk. 

Dr Jacqueline Dohaney, IAD. Email: J.dohaney@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 [1, 2]. ZJE hosts ~600 undergraduate students on two dual-award, research-led 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 intercultural learning. We will explore diverse themes such as teaching staff and student’s practices, motivations, agency, identity and sense of 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 intercultural learning.

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. The supervisory team has strong links with the Institute for Academic Development at the University of Edinburgh, which has international recognition in T&L research. 

Approaches used in project

First, the student will carry out a systematic review of TNE research to identify knowledge gaps. Informed by the review and in alignment with ZJE’s research priorities, the student will then identify the focus of their investigation. Their project will likely 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

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

(2) www.britishcouncil.cn/en/programmes/education/higher/TNE


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