This innovative programme offers research PhDs in medical sciences and translational research topics from across the College of Medicine and Veterinary Medicine. Projects will start in September 2020.
The University of Edinburgh
The UoE is an international leader in fundamental-to-translational medical sciences research, with an outstanding record of interdisciplinarity and innovation, conducted by exceptional researchers offering the highest level of experience in research and PhD training.
The College of Medicine and Veterinary Medicine (CMVM)
CMVM assembles biomedical scientists, medics and vets, working together to play a world-leading role in research to advance understanding of the causes of disease and to develop and deliver new diagnostic, preventative and therapeutic approaches. As the UK’s only unified College of Medicine and Veterinary Medicine, the College consolidates research in multidisciplinary research centres, clustered within contemporary research institutes located next to hospitals on three major translational research campuses. CMVM is committed to recruitment and retention of the most talented early career researchers, and developing the culture of translation of research to maximise impact on health and wealth.
CMVM medical sciences and translational research PhD projects for this Programme are available to students with biomedical sciences , biological sciences and medical sciences backgrounds. These research projects aim to deliver key scientific outputs; utilising fundamental biomedical sciences approaches to discover disease mechanisms, through to developing and implementing new therapies or approaches targeting human or animal health.
PhD research will be supported by experienced PhD supervisors and a PhD Thesis Committee. Supervised laboratory-based research is scaffolded and supported in the early years, leading to autonomous and effective learners in the later years, complemented by group meetings and research seminar attendance / presentation, written reports and manuscript preparation, journal clubs, conference attendance, and mentorship opportunities.
Please note that when you apply to join the Programme you are not choosing a specific supervisor. Students chosen to join this programme will subsequently select a PhD project from an expanding portfolio of potential projects based at Research Centres and Institutes across the College of Medicine and Veterinary Medicine.
PhD students will be located at the institute of their selected primary supervisor, with access to internationally excellent facilities, technical support and supervision appropriate for their specific project.
Participating Centres/Institutes include researchers at:
- Centre for Inflammation Research
- Centre for Clinical Brain Sciences
- Centre for Regenerative Medicine
- The Anne Rowling Regenerative Neurology Clinic
- MRC Centre for Reproductive Health
- Centre for Cardiovascular Science
- The Roslin Institute
- Usher Institute for Population Health Sciences and Informatics
Research projects available in 2020 are listed below.
At application, students will be invited to indicate up to three projects, or supervisors, that most interest them. Student selection for programme entry will be a competitive process, after which the selected students will be invited to choose their research project from the available options in discussion with their preferred supervisors.
Primary supervisor: Dr Sari Pennings (CVS)
Collaborators: Professor Nicholas Mills (CVS, Usher Institute)
Lower cardiac troponin (a heart muscle marker) diagnostic thresholds for myocardial infarction have been linked to improved patient outcomes. Increasingly sensitive assays can exclude a myocardial infarction diagnosis below the low risk threshold1. For patients at intermediate risk below the diagnostic thresholds, the damage and treatment pathways remain uncertain. High-sensitivity assays allow for intermediate risk stratification in patients with suspected acute coronary syndrome, with refinement by additional clinical characteristics. New blood biomarkers are needed to further improve diagnostic discrimination between myocardial injury types. Building on this expertise, we aim to develop cardiac epigenetic assays for clinical translation.
Myocardial injury or cardiometabolic risk is associated with a detection of higher levels of circulating cell-free DNA compared to healthy individuals, a potential diagnostic biomarker that can report specifically on cardiomyocyte damage2. Circulating chromatin fragments originate from apoptosis and therefore directly evidence tissue injury3. This PhD study aims to develop blood assays for epigenetic biomarkers4,5, to test their potential for stratifying intermediate risks and understanding early vs. reversible myocardial injury. Furthermore the study will investigate how epigenetic mapping of circulating cell-free DNA and chromatin markers including antibody based immunoassays can report on epigenetic profiles of the original cells’ disease state6.
- Anand, A et al. A look back: diagnosing myocardial infarction in the era of high-sensitivity troponin after the High-STEACS trial. Cardiovasc Res. 2019 doi: 10.1093/cvr/cvz274.
- Zemmour, H et al. Non-invasive detection of human cardiomyocyte death using methylation patterns of circulating DNA. Nat Commun. 2018 doi: 10.1038/s41467-018-03961-y.
- Aguilar-Sanchez, C et al. Cardiac Stem Cells in the Postnatal Heart: Lessons from Development. Stem Cells Int. 2018. doi: 10.1155/2018/1247857.
- van de Lagemaat, LN et al. CpG binding protein (CFP1) occupies open chromatin regions of active genes, including enhancers and non-CpG islands. Epigenetics Chromatin 2018. doi: 10.1186/s13072-018-0230-0.
- Paris, J et al. Targeting the RNA m6A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia. Cell Stem Cell. 2019. doi: 10.1016/j.stem.2019.03.021.
- Beaujean, N et al. Antibody-Based Detection of Global Nuclear DNA Methylation in Cells, Tissue Sections, and Mammalian Embryos. Methods Mol. Biol. 2018. doi: 10.1007/978-1-4939-7481-8_4
- Shah, ASV et al. Patient selection for high sensitivity cardiac troponin testing and diagnosis of myocardial infarction: prospective cohort study. BMJ 2017. doi: 10.1136/bmj.j4788.
The PhD supervisory team’s extensive complementary expertise in public engagement with research includes novel activity design, media communication including cinematography for public impact, engagement with patient support groups, and patient engagement panels contributing to clinical trial design. Our Centres are leading on clinical and biomedical public engagement and offer an environment, in which PhD student-led engagement can thrive. The student will interact with audiences relevant to this research: patients and families support groups, funders and charities, the general public, and health care policy makers.
As PhD student you will develop a programme of public engagement for impact, exploring different ways of engaging. Our clinical studies offer an opportunity to evaluate impact of patient engagement on trial design and also trust7, by analysing data from this exemplar of ‘research co-production’ towards clinical research outcomes. Our research addresses important issues in health equity, such as gender- differences in clinical research, and social and healthcare provision in the community, where chronic heart failure affects older and economically disadvantaged sections of society. These and the growing health care burden of cardiovascular disease on health care systems require further analysis and inquiry grounded in theoretical frameworks of ‘knowledge to action’ and ‘learning health systems’.
The PhD student will develop public engagement activities with research, with patient groups and other interest groups. Focusing on what occurs 'When Heart Cells Die', audiences will learn how patients' blood samples have contributed diagnostic markers improving long term treatments, highlighting the importance of ongoing research to find DNA biomarkers that can detect heart injury earlier and understand how this differs from healthy heart exertion.
Primary supervisor: Professor Cathy Abbott (IGMM)
Additional supervisors: Dr Sue Fletcher Watson (CCBS)
Over the last 7 years, over a hundred children worldwide have been given a diagnosis of “EEF1A2”, meaning that they have (usually) a heterozygous de novo mutation in the gene encoding a neuronal translation factor, eEF1A2. This means little to most families, and furthermore presents significant challenges for clinicians caring for patients and the scientists working on the disorder, as there are over 40 distinct mutations, all resulting in neurodevelopmental disorders of wildly varying severity and with little known about prognosis. In the lab side of this project we will use our cell and animal models of the disorder generated by CRSIPR/Cas9 gene editing to look at genotype/phenotype correlations, to start to explore different therapies (ranging from drug screens to different forms of gene therapy) and to try to understand more about the long term effects of the different mutations. In parallel, educational and other resources will be developed in consultation with the families of those affected.
- Lam, WW et al. Novel de novo EEF1A2 missense mutations causing epilepsy and intellectual disability. Mol Genet Genomic Med, 2016. doi
- Lopes, F et al. Identification of novel genetic causes of Rett syndrome-like phenotypes. J Med Genet, 2016. doi
- Cao, S et al. Homozygous EEF1A2 mutation causes dilated cardiomyopathy, failure to thrive, global developmental delay, epilepsy and early death. Hum. Mol. Genet., 2017. doi
The main audience for engagement in this project will be the families of affected children (and where possible the children themselves). Much of the content of our website (https://eef1a2epilepsy.com/) has been generated in response to questions from parents, in an attempt to explain the underlying basis for the disorder. As the developer of the only website devoted to the disorder we are in contact with the majority of families around the world, and are well placed to engage with them and consult on what they would like to see in future, whether therapeutic developments or educational resources. What the student will start with, in response to a pilot project that was conducted using a survey and interviews, is the development of a downloadable leaflet giving information about the disorder that can be shared with extended family and friends, and a brief card that can be handed out to explain the condition to strangers. They will also help to develop an FAQ section of the website after surveying families on what their questions are, integrating this information with their decisions on where to focus their lab work.
Primary supervisor: Professor Debby Bogaert (CIR)
Microbiomics is a new and promising field of research that, over the last decade, has elicited exiting new information that may be used to improve health. To this purpose, scientific information needs to be translated into new treatment and preventive strategies. We and others have found extensive evidence that the microbiome assembly in early life is crucial for protection against respiratory infections and inflammation. The exact mechanisms by which identified biomarker commensal species elicit protection is unknown, which is essential to help understand how we can translate this mechanism into succesful treatment and preventive strategies.
We recently invested in establishing a toolset to study 1. the interactions between commensals and pathogens to decipher direct microbial competition, and 2. to study the role of the host mucosa and innate immune cells in the commensal-mediated effects on infection, inflammation and invasion. This project will use these models to study host-microbiome interactions underpinning mechanisms of protection against viral, bacterial and mixed infections. The findings will directly inform the design of a next generation of biotherapeutic products to prevent and treat (recurrence of) infections and chronic inflammation.
- Man, WH et al. The microbiota of the respiratory tract: gatekeeper to respiratory health. Nat Rev Microbiol. 2017. doi: 10.1038/nrmicro.2017.14.
- Hakansson, AP et al. Bacterial-Host Interactions: Physiology and Pathophysiology of Respiratory Infection. Physiol Rev. 2018. doi: 10.1152/physrev.00040.2016.
- Dominguez-Bello, MG et al. Role of the microbiome in human development. Gut. 2019. doi: 10.1136/gutjnl-2018-317503.
Our recent work has identified a wide set of environmental and nutritional risk factors for aberrant microbiome development in early life. Education of the general population, as well as health care professionals community, will create awareness on what parents, family and professionals like midwives, GPs, and community nurses can do to support a healthy microbiome development in mothers, infants and children. Since this health topic and the target population is very broad, and in general not easily reached by patient groups, we require more general educational tools to share the educational information.
We therefore aim to create a series of fun educational materials with a returning (set of) characters visualizing the messages we’d like to share with the public, created under university logo to underwrite the trusted source. These animations and messages will not only serve to educate the public on the function of their own microbiome and how it supports health, but also help us understand their perception of this topic, discover what they would want to know, and what they would find acceptable in the way of microbiome interventions. These can be disseminated through for example social media and by display on posters, leaflets etc. to serve different publics, i.e. GPs, nurse, schools etc. These will be supported by short movies where we use visual (same themes/characters as cartoons) and verbal material to share in a fun, entertaining and simple way the discussed information. These short movies will again be disseminated through our own trusted channels.
Primary supervisor: Dr Megan G. Davey (Roslin Institute)
This project seeks to illuminate the genetic networks which control the development of the forearm, particularly posterior-anterior (ulna-radius) patterning, in order to understand the pathology of the abnormal limb, to improve genetic diagnosis and counselling, to inform patient management and treatment and to add to our overall knowledge of the mechanisms of embryonic development. Using developing chicken embryos as our primary model, we will utilise genome engineering to model genetic loci known to be causative of abnormal forearm development in human but which are difficult to study in other models, in particular FANCA, FANCC as well as the long range-enhancer of SHH.
- Davey, MG et al. Illuminating the chicken model through genetic modification. Int J Dev Biol. 2018. doi: 10.1387/ijdb.170323mm.
- Lam, WL et al. Experimental evidence that preaxial polydactyly and forearm radial deficiencies may share a common developmental origin. J Hand Surg Eur Vol. 2018. doi: 10.1177/1753193418762959.
Abnormal limb development - particularly of the hand and foot - is common. Intensive research over the last five decades has illuminated the genetic and environmental causes of many of these congenital differences. There has, however, been a failure in communication and engagement between the three major stakeholders; the patients, research scientists and clinicians. The translation of the fundamental scientific discoveries and ideas to clinical practise, has been slow, partially due to a lack of collaboration between the scientific and clinical fields. Moreover the needs of patients have often not been considered important factors in experimental design, nor has there been a drive to translate technical scientific findings into accessible formats for either clinicians or patients. Thus patients with congenital limb differences are often unaware of the causes of their differences and their significant and important place in understanding the laws of developmental biology.
Within this PhD project we aim to:
- Hold two patient and family focused Scientific Workshops at Easter Bush Science Outreach Centre (EBSOC). Patients will be invited through Mr Lam’s Out-patient surgeries and by contacting relevant charities (Reach, LimbPower) These Workshops will be developed in collaboration with Nicola Stock and Jayne Quoiani and will serve to bridge the link between research scientists and patients/families through interactive demonstrations of the techniques we use to understand limb development (particularly sequencing, chicken embryo manipulation and whole mount gene expression analysis in the embryo). We will encourage an open forum between participants to discuss what their limb differences mean to them; what they would like research to help them understand/prevent/improve about their limb difference; and what resources they would like to be made avaible to help explain the cause of their limb difference to others.
- Expectations of participants will be assessed before and after the Workshop, and a summary of Outcomes will be distributed to all participants after the event. We expect that this work will also be presented at a specialised Hand Surgery Conference (e.g. Autumn BSSH conference). All non-invited participants (e.g. the scientific staff), will undertake PE Best Practice training, which has been developed by The Roslin Public Engagement Team.
- Based on the outcomes of the Workshop we will develop accessible literature and web content on the most common genetic causes of congenital limb differences- particularly pre-axial polydactyly and phocomelia. Importantly, this content will positively celebrate congenital limb differences. We will ask those accessing the online content to undertake an optional questionnaire, regarding the what research they would like to help them understand/prevent/improve their limb difference, which we will analyse and use as evidence for future experimental design.
Primary supervisor: Professor Donald J. Davidson (CIR)
Respiratory viral infections are a cause of significant mortality and morbidity. Few effective interventions exist to use against viruses for which vaccines are not available. Respiratory Syncytial Virus (RSV) is the major cause of lower respiratory tract infection worldwide, infecting ~64 million people/year globally. RSV infection causes ~3.2 million hospital admissions/year in children <5 years old, and ~160,000 deaths/year worldwide. No effective treatments for RSV exist and there is no vaccine currently available. We have discovered that cathelicidin, an inducible antimicrobial host defence peptide (HDP), has potent antiviral activity against RSV (and influenza) when applied therapeutically, both in vitro and in mice. Furthermore, induction of native cathelicidin is essential for optimal protective responses against RSV in mice, cathelicidin expression in humans is associated with protection against RSV infection, and expression may be modified by host microbiome.
Therefore, cathelicidins have exciting promise, used as future therapeutics or by targeting induction of native peptide expression. This project proposes to: a) examine commensal microbial and chemical (including small molecule screens) inducers of native cathelicidin, to assess efficacy in enhancing host defence against infection with RSV, influenza and other respiratory viruses, as potential future preventative interventions, and b) screen cathelicidin-related peptidomimetics as possible future therapeutics for active disease.
- Currie, S et al. Cathelicidins have direct antiviral activity against respiratory syncytial virus in vitro and protective function in vivo in mice and humans. J. Immunol. 2016. doi: 10.4049/jimmunol.1502478.
- Mansbach, JM et al. Serum LL-37 Levels Associated With Severity of Bronchiolitis and Viral Etiology. Clin. Infect. Dis. 2017. doi: 10.1093/cid/cix483.
- Barlow, PG et al. Antiviral Activity and Increased Host Defense against Influenza Infection Elicited by the Human Cathelicidin LL-37. PLoS One 2011. doi: 10.1371/journal.pone.0025333.
- Gwyer Findlay, E et al. Exposure to the antimicrobial peptide LL-37 produces dendritic cells optimized for immunotherapy. Oncoimmunology 2019. doi: 10.1080/2162402X.2019.1608106
- McHugh, BJ et al. Cathelicidin is a "fire alarm", generating protective NLRP3-dependent airway epithelial cell inflammatory responses during infection with Pseudomonas aeruginosa. PLoS Pathog. 2019. doi: 10.1371/journal.ppat.1007694.
This project is expected to focus on patient involvement around the topic of RSV infections, and schools/public engagement around more general immunology and infection topics.
Current projects, collecting clinical samples to study cathelicidin expression, RSV infection and the influence of upper respiratory tract microbiota, provide access to relevant clinical cohorts. These include: a) infants and their carers who experience severe RSV infection, b) premature infants (who are at increased risk of RSV infection) and term infants, and their carers, as part of the Theirworld Edinburgh Birth Cohort. These groups will be engaged to involve them in developing an understanding of the evident unmet needs for patient-information during RSV infection, after infection (e.g. increased risk of wheeze and asthma) and in high risk infants, and their perspectives on preventative and therapeutic approaches that would be acceptable/welcomed in the future. Resources and events will then be developed, using co-production methods, to meet these needs, and information applied to future novel intervention development.
Events and resources available (including Prof. Davidson’s Supercytes project, and Amazing Immunology Science Festival, schools, EBSOC workshops) can also be used, adapted and developed by the student to engage around general immunology and infectious disease topics, including viral infection ,vaccination, microbiome, antibiotic resistance and basic immunology.
Primary supervisor: Professor Julia Dorin (CIR)
The alarming rise in antimicrobial resistance (AMR) means that the search for new antimicrobials with novel action is a priority area. Throughout eukaryotes, host peptides arise that have antimicrobial ability against invading pathogens and these are released upon pathogen challenge. One class of antimicrobial peptides (AMP) are defensins which are a multi-gene family in many species and in human have a copy-number variable cluster. These are variably potent AMP that are slow to develop antibiotic resistance, but also have additional functions including acting as promiscuous ligands and influencing innate immune cell function. This project seeks to validate Drosophila melanogaster as a genetically tractable and ethically acceptable system to determine the in vivo antimicrobial effect of defensin AMP against clinically important pathogens including multidrug resistant strains. We have obtained Crispr/Cas9 generated, AMP-deleted (AMP) pathogen-sensitive flies, which allows both Gram positive and negative clinical, bacterial strains to infect embryo, larvae and adult flies.
The student will determine bacterial killing of ESKAPE pathogens including those that exhibit multidrug resistance, by defensin-derived peptides alone or in combination with other AMP or antibiotics. In addition, live imaging will enable visualisation of the innate cellular response to pathogen challenge in real time and gain knowledge on the interactive function of mammalian AMPs with insect haemocytes (monocyte/macrophage equivalents). Finally, a macrophage culture model of human induced pluripotent stem cells (iPSC) macrophages will be used to complement the fly experiments and demonstrate translational relevance and therapeutic potential.
This project provides several possible areas for public engagement including (i) the danger of antimicrobial resistance; (ii) reducing use of vertebrates in experimentation and (iii) appreciation of macrophages in bacterial killing and wound resolution. The student will choose which area they feel most passionate about to take forward. Antimicrobial resistance is a major problem worldwide, is increasing in low and middle income countries and requires urgent, ongoing action to reduce inappropriate antibiotic use. This is particularly true in livestock as the growth advantage of animals treated with some antibiotics means farmers are loathe to stop their use particularly as high density livestock farming increases. The EU will ban the use of preventative antibiotics in 2020, but the UK government in its 5 year (2019-2024) national action plan did not confirm that it will follow suit. In addition, the UK is currently open to importing meats and dairy from countries that use higher levels of antibiotics than the UK. Student will apply to join Medical Research Foundation cohort of AMR students and use this to enhance engagement opportunities.
Engagement activities should be giving the same strong message but levelled at various audiences eg. a game for primary children; an interactive play for secondary students (particularly those in rural areas such as East Lothian); talk and play for members of the public through “Lets talk about health” lecture series and other Science fairs; fact slide for biology teachers in local schools eg. Castlebrae high School; presentation to Members of Scottish Parliament eg. Mairi Gougeon (Minister for Rural Affairs and Natural Environment), as well as rural Scottish Westminster MPs to influence consideration of UK and Scottish policy on farming antibiotic use to influence policy.
Primary supervisor: Dr Elaine Emmerson (CRM)
Additional supervisors: Dr Tilo Kunath (CRM)
Despite being a life-saving treatment for patients with head and neck cancer, a side-effect of radiotherapy is damage to salivary glands, leading to the chronic condition xerostomia, or dry mouth (Emmerson, et al. 2018). Patients with xerostomia can experience severe difficulties eating and speaking and data collected by The Swallows Trust indicates that while most head and neck cancer patients experience xerostomia, 78% were not prepared for the impact on their quality of life (Curtis, et al. 2018). This side-effect of cancer treatment is vastly underappreciated and understudied.
To date, no restorative treatment for xerostomia exists. Alongside current efforts in the Emmerson lab to study the regenerative capacity of the salivary glands following radiotherapy, this PhD project will focus on determining if a pharmacological approach can also prevent or reduce radiation-induced damage to the glands. Testing the effects of compounds that protect against free radical-mediated damage, the student will use ex vivo cell assays using human patient-derived salivary glands, alongside a well-validated murine model of therapeutic irradiation, combined with functional readouts (e.g. saliva production) and in-depth analysis (e.g. RNA-seq, lineage tracing), to understand the mechanisms of damage prevention.
The scientific content of the PhD will be complimented with stakeholder engagement throughout the project, which will include communication with head and neck cancer patients, particularly those who are yet to start radiotherapy, healthcare professionals (radiologists and oncologists) and patient support groups. In addition, the project will engage with G-Lands: an out of body experience, a collaborative project between the Emmerson lab and artist Emily Fong, in partnership with ASCUS Art and Science, following the salivary gland specimen on its journey from patient to laboratory.
- Emmerson, E et al. Salivary glands regenerate after radiation injury through SOX2-mediated secretory cell replacement. EMBO Molecular Medicine 2018. doi: 10.15252/emmm.201708051.
- Curtis, C et al. Patient reports of mouth symptoms after radiotherapy treatment for Head & Neck Cancer: An International Study. European Medical Journal 2018. doi: 10.1093/annonc/mdy287.
The project will have measurable outcomes for both the scientific content and the engagement content. The ultimate scientific outcome will be to prevent or ameliorate xerostomia. The engagement outcome will be focussed on reducing the high level (78%) of patients that were not prepared for the impact of xerostomia. This will involve evaluating patient understanding and preparedness in a local cohort (e.g. throughout NHS Lothian) throughout the 4 years of study.
At present there is very little engagement between head and neck cancer patients and the healthcare professionals they do not come in to direct contact with during their treatment (e.g. pathologists, scientists). This project will involve the student interacting with a diverse team of partners, including a local patient support group, The Throat Cancer Foundation, and patients and their families; and healthcare professionals involved in the treatment of head and neck cancer, including oncologists, surgeons, radiologists, pathologists and dentists; and promoting multi-way communication between these groups. It will inspire scientists and clinicians to engage from beyond the laboratory or hospital, and provide a voice for head and neck cancer patients.
The student will present their data at national and international conferences, will publish their research in both scientific journals and public engagement journals and will be directly involved in producing informative material for patients and healthcare professionals, which will be printed and distributed in clinic and hospital settings and through patient support groups.
Primary supervisor: Dr Gwo-tzer Ho (CIR)
Crohn’s disease (CD) is a debilitating and incurable condition, which is projected to affect 10 million individuals by 2025. We aim to investigate the role of mitochondrial formylated peptides (mFPs) as a host-derived damage associated molecular pattern (DAMP) in innate immunity1. Mitochondria, intracellular organelles responsible for cellular energy production, are descended from bacteria. They have autonomous protein synthesis machinery, with mFPs similar to bacteria. When released extracellularly, they are recognised by formylated peptide receptor-1 (FPR1), which is evolutionarily considered as the receptor for Yersinia pestis, the causative bacteria for the plaque2. Recent Western pandemics (e.g. Black Death) with high mortality have shaped population genetics as variants of FPR1 gene can protect against plaque. This is less relevant with the discovery of antibiotics. In parallel, CD has emerged as a major disease-entity in the 20th century. Of interest, human genetic and transcriptomic studies point to a role of FPR1 in the macrophage in CD3,4.
We have shown that
- High levels of mFPs are found in active disease;
- Recruited monocyte-macrophage populations in CD are marked with high FPR1 expression;
- FPR1-deletion is protective in experimental colitis.
These data provide the hypothesis that abnormal FPR1 activation by host-derived mFPs (as opposed to bacteria) is a key pathogenic factor that shapes the pro-inflammatory phenotype of the macrophage and importantly, is a therapeutic target for CD.
In this PhD, the applicant will investigate
- the mechanisms of mFPs on monocyte-macrophage function,
- the influence of genetics on mFP-FPR1 signalling,
- the translational potential of modulating this pathway in CD.
This project will have a strong focus on human CD subjects with mouse transgenic work in the Gut Research Unit with macrophage (Calum Bain) and FPR1-signalling (Adriano Rossi) experts.
- Boyapati, RK et al. Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications. Mucosal Immunology 2016. doi: 10.1038/mi.2016.14.
- Osei-Owusu, P et al. FPR1 is the plague receptor on host immune cells. Nature 2019. doi: 10.1038/s41586-019-1570-z
- Peters, LA et al. A functional genomics predictive network model identifies regulators of inflammatory bowel disease. Nature Genetics 2017. doi: 10.1038/ng.3947
- Martin, JC et al. Single-Cell Analysis of Crohn's Disease Lesions Identifies a Pathogenic Cellular Module Associated with Resistance to Anti-TNF Therapy. Cell 2019. doi: 10.1016/j.cell.2019.08.008
We have a strong track record in human IBD studies. However, despite more than 4000 participants (2010-2020) in various scientific studies in Edinburgh, we do not have a formal patient and public involvement (PPI) plan. In 2019, I set up the Edinburgh IBD Science group and the Gut Research Unit in CIR. This time, an active decision was made to build a vibrant PPI approach bringing together Science and IBD, with examples:
- Our own PPI group in IBD CIR (led by K McGuire) that strong involvement in our UK –wide randomized clinical trial (MARVEL) in UC; and the CD cohort (MUSIC) study.
- Notable media coverage in BBC and ITV news; Times, Telegraph and Daily Mail on our publications.
- Close PPI alignment with UK IBD Charities (Crohn’s Colitis UK and Guts UK), major funders of our work.
- Public lecture ‘Let’s talk health: Healing the damaged gut in IBD: From the patient, scientist and doctor’ in February 2020. In this talk, I have involved a current PhD student as a main presenter to demonstrate the importance of ‘grass-root’ engagement with the public.
In this project, the PhD applicant will be given the opportunity to:
- Develop a dedicated PPI program where patients/participants are embedded in our Science-to-Medicine work.
- This group will be allowed to follow our laboratory progress meetings with a prospect to offer scientific direction, first-hand interaction with data and oversight into future clinical studies.
- The PhD applicant will work with one of our current PPI patient (a training journalist) to develop a public-facing regular media forum (3-4 months) with ‘on the ground’ updates on our IBD work, from a patient and scientist perspective.
- This plan will have an expansive theme from basic science (the lab), ideas and data (lab meeting), human studies (in the hospital), the scientific process (what happens after a patient donates his/her sample) to the clinical trial (the workings of our drug trials team).
- The main target will be IBD patients, public participants in any scientific studies but this platform can be opened up to secondary school students, teachers and career development teams.
The aim is to put the patients at the heart of the dynamic progress of our scientific work. The candidate will work alongside our existing IBD and also CIR PPI team.
Primary supervisor: Professor Andrew Horne (CRH)
The overarching objective of this project is to investigate the role of immunometabolism in endometriosis a neuro-inflammatory condition that affects 10% of women of reproductive age. There is strong evidence that macrophages play an important role in the aetiology of the disorder but we do not know anything about their metabolic status nor how this is influenced by the unique microenvironment found in extra-uterine endometriosis lesions. The student will use human tissue samples and pre-clinical laboratory models to investigate metabolic changes in immune cells present in the pelvis and in endometriosis lesions. A secondary aim of the project will be to build on these studies by screening clinically available drugs developed to treat other inflammatory conditions in relevant animal models to evaluate their impact on the extent of endometriosis and pain perception. Any drug compounds identified could then be fast-tracked to clinical trials because they have already been approved for treatment in another disease providing new opportunities to benefit patients.
- Horne, AW et al. Endometriosis. Cell 2019. doi: 10.1016/j.cell.2019.11.033
- Horne, AW, et al. Repurposing dichloroacetate for the treatment of women with endometriosis. Proc. Natl. Acad. Sci.USA 2019. doi: 10.1073/pnas.1916144116
- Forster, R et al. Macrophage-derived insulin-like growth factor-1 is a key neurotrophic and nerve-sensitizing factor in pain associated with endometriosis. FASEBJ 2019. doi: 10.1096/fj.201900797R.
- Greaves, E et al. Relevant human tissue resources and laboratory models for use in endometriosis research. Acta. Obstet. Gynecol. Scand. 2017. doi: 10.1111/aogs.13119.
The EXPPECT team led by Profs Horne and Saunders works closely with patients and organisations including Endometriosis UK who are committed to improving the lives of women with endometriosis. The team have an active programme of engagement with the public, patients and policy makers which aims both to raise awareness of the disorder and to inform and support patients and their family members by holding regular patient research days. The student will be able to participate in these ongoing initiatives and other public engagement activities including:
- the Edinburgh International Science Festival, an annual event with almost 300 meetings in venues around Edinburgh enabling researchers to discuss their work with the wider public.
- ‘Pint of Science’ Festival, an event which allows researchers to present their work to the general public in a less formal setting.
- ‘Endometriosis UK Research Conference’, an annual event where researchers to present their work to 100-120 women with endometriosis (and their partners), events are held around the UK, including Edinburgh.
The student will receive support from the MRC Centre for Reproductive Health public engagement officer and have the opportunity to join activities that are engaging with schools.
Primary supervisor: Dr Veronique Miron (CRH)
Additional supervisors: Professor Anna Williams (CRM)
Injury to the developing infant brain during gestation or birth often leads to impairments in sensation, intellect and movement (e.g. cerebral palsy). Although cerebral palsy affects 17 million people, the basis of injury is poorly understood, and there are no reliable biomarkers of injury nor treatments for brain repair. Due to better survival of injured infants in recent decades (albeit with increasing prevalence of disability), there is low availability of tissue which has hampered research. However, we have obtained a tissue bank which uniquely allows for the first comprehensive assessment of human infant brain injury. Using state-of-the-art large-scale analysis of tissue proteins and mRNAs (using digital spatial profiling), we aim to i) identify biomarkers associated with areas of brain injury vs health, and ii) understand gene/protein signatures underpinning injury. This could lead to improved clinical assessment following suspected injury, and reveal novel therapeutic approaches to support healthy brain development.
Engagement of the general public and patient groups regarding human infant brain injury/cerebral palsy research is underdeveloped in comparison to that for adult neurological disorders. This project thus creates the opportunity to improve public knowledge on research in this area, by capitalizing on pathways established by the Miron lab which can be further developed by the student:
- Social media: using Twitter (eg @MironLab) to discuss research, engage with patient groups, and inform on issues in research. The student can also engage through Edinburgh Neuroscience (@EdinUniNeuro).
- Direct interactions with stakeholders: the student can interact with patient groups via TheirWorld based in our centre (eg at public symposia) and with the general public via talks, hosting school students (Science Insight programme) and participating in the Edinburgh Science Festival. The opportunity exists to engage with a network of clinicians working with children with cerebral palsy based at the Sick Kids hospital on-site.
- Creation of resources for the public: the student will have the opportunity to create resources for websites (SaveOurBabies, EuroStemCell) and magazines (National Family) such as drawings, blogs, and interviews.
Primary supervisor: Dr Rod Mitchell (CRH)
Current treatments for childhood cancers and testicular tumours in adults can compromise fertility. Gankyrin is an oncogene involved in the pathogenesis of several cancers. We have recently shown that inhibition of gankyrin signalling enhances tumour cell death and reduces requirement for gonadotoxic chemotherapy in a testicular cancer cell line1.
We hypothesise that downregulation of gankyrin signalling is an effective adjuvant treatment for testicular cancer in adult men. Conversely, we hypothesise that upregulation of gankyrin in healthy germ cells of prepubertal testis can reduce their sensitivity chemotherapy-induced damage.
The project involves validated models (in-vitro, xenograft) of testicular development and function utilising human fetal, prepubertal, adult and testicular cancer tissues2,3. We will determine the in-vitro effects of several recently identified small molecules (SM) that target gankyrin4 on normal testis and testicular cancer tissues. SM treatments will also be combined with chemotherapy to determine their potential as an adjuvant to chemotherapy in testicular cancer, and the potential for these SMs to reduce chemotherapy-induced germ cell damage in the prepubertal testis. SMs that alter cell response to chemotherapy will be taken forward into mechanism-of-action to demonstrate the anti-cancer signalling pathways perturbed and in-vivo efficacy studies involving xenografting of human tissues.
- Camacho-Moll, ME et al. The oncogene Gankyrin is expressed in testicular cancer and contributes to cisplatin sensitivity in embryonal carcinoma cells. BMC Cancer. 2019.
- van den Driesche, S et al. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model. Science Translational Medicine. 2015.
- Jørgensen, A et al. Nodal Signaling Regulates Germ Cell Development and Establishment of Seminiferous Cords in the Human Fetal Testis. Cell Reports 2018.
- Kanabar, D et al. Structural Modification of the Aryl Sulfonate Ester of cjoc42 for Enhanced Gankyrin Binding and Anti-cancer Activity. Bioorg. Med. Chem. Lett. 2019.
Preventing long-term morbidity after cancer treatment and developing strategies to preserve fertility is of scientific, clinical and public interest. This provides far-reaching opportunities for engagement with a wide variety of stakeholders including cancer patients, cancer/fertility charities, policy makers, and pharmaceutical/fertility industries. The research group attracts frequent national/international attention for work in this area, including for the BBC. The CRH recently ran an MRC-funded open day for schoolchildren in which PhD students led organisation and delivery of a fertility preservation programme. The group also has frequent interaction with public engagement teams locally (CRH, University Press Office), nationally (Science Media Centre) and internationally (Fertility Europe), providing opportunities for the student to develop their ideas and broaden experience of engagement.
We will continue to work closely with national charities e.g. Children with Cancer UK (CWCUK) and CLIC Sargent, to raise awareness and develop a two-way interaction with stakeholders (e.g. workshops, patient forums). Previous activities included producing a public information ‘Doodle’ video for the CWCUK website. The Carragher group has multiple interactions with pharmaceutical and biotech industry representatives and life science investors and is active in promoting academic-industry networking and industry secondments, providing the student with further opportunities for engagement.
Primary supervisor: Professor Chris Ponting (IGMM)
Additional supervisors: Professor Sarah Cunningham-Burley (CBSS)
Myalgic encephalomyelitis (ME) or chronic fatigue syndrome (CFS) is a long-term, fluctuating, multi-system condition that affects all age groups and all ethnic and socioeconomic strata. People with ME/CFS experience severe, persistent fatigue associated with post-exertional malaise, the body’s inability to recover after expending even small amounts of energy, leading to a flare-up in symptoms. An estimated 250,000 people are affected by ME/CFS in the UK and it is the greatest cause of school absenteeism. As recognized by the NICE guidance, there is no test to diagnose ME/CFS and no known cure. The ME/CFS community is underserved, neglected and woefully misunderstood by society.
This project will contribute population genetics analysis to a UK genome-wide association study (GWAS) of 20,000 people with ME/CFS that seeks to reveal the genetic predisposition of this devastating disease. Simultaneously, the PhD student will chronicle the challenges and successes in how patients, carers, public and scientists join together to achieve a common aim. The influence of genetic findings on patients and the public, and the influence of people with lived experience of ME/CFS on scientists, will be captured as they occur in real time. It is expected that perspectives of clinicians, GPs and the general public will be irrevocably transformed by this study and by ME/CFS genetic findings.
- Committee on the Diagnostic Criteria for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (2015) Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome. Redefining an illness. https://www.nap.edu/read/19012/chapter/1
We define patient-public involvement (PPI) in this research as being carried out with or by members of the public rather than to, about or for them. Partners of this UK genetics project include Forward ME charities and a cofounder of the Science for ME website. Recruitment of 20,000 people for the genetics study requires an exceptionally high level of engagement of a marginalised community. Two PPI members are co-investigators on the NIHR-MRC funding proposal. There is no aspect to this project that does not require Involvement which calls for high levels of effective dialogue among patients, public and scientists.
The successful PhD applicant would work alongside human geneticists, people with ME/CFS, carers, public relations or marketing experts, charity sector workers, politicians and communications experts to capture the successes and difficulties in addressing questions such as: (i) what are the different perspectives on the causes of ME/CFS, (ii) why is there no diagnostic test or cure and what does this mean for the lived experience and treatment of the disease, (iii) why are ME/CFS symptoms commonly disbelieved, and how does this impact on both patients and health care professionals, and (iv) what expectations do the range of stakeholders have of collaboration and partnership and how do these influence involvement and engagement?
Primary supervisor: Professor Rebecca Reynolds (CVS)
Additional supervisors: Professor Fiona Denison (CRH)
Gestational diabetes (GDM) is one of the commonest pregnancy complications. GDM poses significant risks to the immediate and long-term health of both the mother and child. For mothers, GDM is associated with a 7-fold increased risk of type 2 diabetes in later life. For the fetus, uncontrolled GDM leads to accelerated fetal growth, increasing the risk of macrosomic, large-for-gestational age neonates and diabetes in later life1. Hence it is essential to implement effective clinical interventions to maintain glucose control in pregnancy. The tablet metformin is widely used to control glucose levels in women with GDM but its use is controversial with preliminary data indicating the potential for adverse effects on fetal growth. In this project we plan to utilise data from our established database of women with gestational diabetes2 and linked Edinburgh Reproductive Tissue Biobank of blood samples through pregnancy and placental samples at delivery, including from our randomised controlled trial of metformin in pregnancy3. The rich data includes deep clinical phenotyping such as demographics, pregnancy complications, fetal ultrasound data, laboratory data, birth outcomes and bioresource. We will determine the impact of metformin on fetal growth trajectories and explore the underlying mechanisms. We will also compare the outcomes of metformin compared with other treatments including diet and insulin. Such work has potential to change clinical practice with respect to management of GDM.
- Johns, EC et al. Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications. Trends Endocrinol Metab. 2018.
- Ryan, DK et al. Early screening and treatment of gestational diabetes in high-risk women improves maternal and neonatal outcomes: A retrospective clinical audit. Diabetes Res. Clin. Pract. 2018.
- Chiswick, C et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2015.
We will engage with pregnant women and their children to inform them about diabetes in pregnancy. Using this network, we plan to identify at least one woman to buddy with the PhD student throughout the studentship. This will enable to student to have real-world exposure to the challenges of having GDM. Furthermore, it will enable the student to co-produce and develop appropriate public engagement strategies in partnership with women with GDM.
The supervisors work closely with the Tommy’s the Baby Charity which is active at promoting information to pregnant women through its website. At the Edinburgh Tommy’s Centre, we frequently host visitors e.g. lay public, fundraisers, potential donors to the Tommy’s Centre, have a public facing facebook page for disseminating information about studies and a quarterly newsletter distributed to community midwives and the staff of Simpson’s Centre for Reproductive Health reporting on research activities. In 2020, we are embarking on a broader impact and engagement strategy across Scotland to demonstrate the power of data-driven and technology enabled research to drive forward innovation for maternal and offspring health. The PhD student will be supported to lead outreach on data-driven approaches to improve pregnancy outcomes in partnership with the supervisors and out charity partners.
Both supervisors recently conducted a public engagement activity with the MRC festival focused on obesity in pregnancy and attracted > 100 participants and GDM would be make an excellent topic for a future event. The topic could also be presented at the University of Edinburgh Public Lecture series (which both supervisors have presented at) attracting local school children and teachers. Reynolds also works closely with Diabetes UK which has a Lay and Health Care Professional forum of more than 2000 members to which the work could be disseminated. Denison works closely with the maternal medicine and intrapartum clinical studies group of the Royal College of Obstetrics and Gynaecology, both of which engage actively with women to inform research and impact.
Primary supervisor: Dr Sinead Rhodes (CCBS)
Young girls with neurodevelopmental disorders such as dyspraxia, ADHD and autism have a much higher vulnerability to developing mental health difficulties in particular depression and anxiety than their peers (c. 50% vs. 12%). An earlier onset of mental health difficulties is also observed in this population; earlier onset often predicts more severe illness trajectories across the life span. A recent James Lind Alliance research priority setting exercise1 conducted by the first supervisor with these young people, their families and practitioners, identified adaptation at times of transitions in these children’s lives as a core research priority area. In this project we will take a multidisciplinary approach to identify the biological (e.g. puberty, menstruation), psychological (e.g. sensory processing, intolerance of uncertainty, cognitive functions) and social (e.g. transition from primary to high-school) factors that put these young people at heightened risk of developing mental health difficulties as they transition from childhood to adolescence.
Young people with these neurodevelopmental disorders, who share many cognitive, psychological and social features in common, will be assessed longitudinally on three occasions from the end of primary (p7) to end of year 1 in high-school (S1) from around age 11-12/13 years. Co-production methods with affected young people will be used to determine design, measures and the nature of outputs to ensure appropriateness and sensitivity and facilitating shared ownership between researchers, the participant group and relevant stakeholders.
- Steward et al. "Life is Much More Difficult to Manage During Periods": Autistic Experiences of Menstruation. Journal of Autism and Developmental Disorders 2018.
- Magnuson and Constantino. Characterisation of Depression in Children with Autism Spectrum Disorders. Journal of Development and Behavioural Paediatrics 2011.
- Lim, AK et al. Joint production of research priorities to improve the lives of those with childhood onset conditions that impair learning: the James Lind Alliance Priority Setting Partnership for Learning Difficulties. BMJ Open 2019. doi:10.1136/bmjopen-2018-028780
The project examines sensitive topics that are of significant health concern for young girls with neurodevelopmental disorders as identified by these young people, their families and relevant stakeholders1. Young people, their parents and practitioners will be involved in co-producing the specific research design and measures to ensure appropriateness and sensitivity of methods. These methods also facilitate shared involvement and ownership of the research between the academic, participant group and relevant stakeholders. Co-production methods are known to be important in empowerment of the participant group which is ultimately vital in ensuring findings are adopted in practice. A key goal of the project, beyond furthering understanding of the factors underlying mental health difficulties in these young people, is the production of resources linked to that knowledge. Here we will work with affected young people themselves and their parents and teachers in facilitating the development of strategies and resources directly focused on mental health. Strategies/resources will also focus on difficulties around the transition to adolescence including puberty, menstruation and moving from primary to high-school, associated with poor mental health outcomes in these young people. Possibilities include development of a targeted online chatroom and infographics suitable for the school environment. The supervision team have a strong track record in the development of public engagement outputs relevant to these sensitive topics and will facilitate the PhD student to develop these outcomes.
1This proposal directly addresses question 10 identified and prioritised in the James Lind Alliance research priority exercise conducted with affected individuals, their families and health and education practitioners: “Which strategies are effective in helping children and young people with learning difficulties live independent lives, including during times of transitions?”
Lim, A.K., Rhodes, S.M., Cowan, K, & O’Hare, A. (2019). Joint production of research priorities to improve the lives of those with childhood onset conditions that impair learning: the James Lind Alliance Priority Setting Partnership for Learning Difficulties. BMJ Open 2019; 9:e028780. doi:10.1136/bmjopen-2018-028780
Primary supervisor: Dr Sarah Stock (Usher Institute)
Additional supervisors: Dr Honghan Wu (Usher Institute)
In the UK around one in 200 babies die in pregnancy or the newborn period. Stillbirth and preterm (birth less than 37 weeks gestation) are the main contributors to these deaths. Pregnancy interventions such as induction of labour and caesarean birth aim to reduce perinatal mortality, but carry their own risks of complications. These interventions also have a major impact on maternity resources and staffing, as well as women’s experience of labour.
The aim of this project is to develop and validate risk prediction tools for pregnancy complications such as preterm birth, stillbirth and caesarean birth. You will interrogate large datasets containing clinical information about pregnancy and newborn health, comparing different model development approaches e.g. logistic regression and other machine learning techniques. You will work with clinicians and parent groups to ensure the risk predictors are relevant to their decisional needs, and incorporate them into decision aids which can help shared decision making and be implemented in electronic health records for use at point of care.
An aim of this project is to produce tools to help shared decision making about care in pregnancy. Making treatment decisions in pregnancy is particularly complex. Decisions are often made on a background of internal conflict (between needs of the mother and of the developing baby) and external pressures (strong societal/cultural influences on childbirth; limited healthcare resource). Opinions from different healthcare providers (midwives, doctors, doulas) can oppose. New legislation (Montgomery versus Lanarkshire) means there is a legal requirement of healthcare providers to ensure parents are aware of ‘material risks’, but there is tension between full discussion and engendering fear.
This project will afford multiple opportunities for parental, clinician and policy maker engagement. For example, collaboration with maternity service users and providers could prioritise the most relevant predictive models to develop, advise on how risk information is best presented and how to disseminate decision aids. Engagement with NHS Digital and Electronic health records companies could help ensure tools can be implemented effectively. Engaging with government (e.g. Scottish Government Stillbirth Subgroup) and guideline developers (e.g. NICE, RCOG) could help ensure the research is impactful. The supervisors have close links to pregnancy charities such as Tommy’s and SANDS, and collaborations with these groups could further enable engagement with maternity service users and policy makers. An existing collaboration with a theatre company (DirtyMarket) could allow additional opportunities for wider public engagement.
Primary supervisor: Professor Anna Williams (CRM)
Additional supervisors: Professor Andrew Baker (CVS)
Brain endothelial cells (ECs) are implicated in a variety of brain diseases, including cerebral small vessel disease (cSVD), through their signalling to the underlying brain including oligodendrocytes. ECs in disease can become ‘dysfunctional’ detectable by increased EC proliferation (amongst other markers). In this state, they secrete substances (including HSP90a) which inhibit the maturation of oligodendrocyte precursors (OPCs) into mature myelinating oligodendrocytes. Reversal of EC dysfunction in vitro reduced HSP90a release and improved OPC maturation, and in vivo normalised cSVD white matter.
Multiple sclerosis (MS) also shows pathology suggestive of the blood vessel and EC involvement with more blood vessels in the vicinity of MS demyelinated lesions2 and angiogenesis3. We also now know that ECs in a mouse CNS model of demyelination (EAE) are dysfunctional using transcriptomics4. This leads to the hypothesis that dysfunctional ECs also contribute to the pathology of MS, adversely affecting the ability of OPCs to mature into myelinating oligodendrocytes, hence limiting one of the routes to remyelination and brain repair.
This project will address this hypothesis using
- bioinformatic analysis of EC heterogeneity and dysfunction from current RNAseq datasets,
- spatial validation on MS and mouse model tissue and
- drug reversal of EC dysfunction, e.g. with simvastatin
in a treatment trial in a demyelinating mouse model, aiming to improve remyelination.
- Rajani, RM et al. Reversal of endothelial dysfunction reduces white matter vulnerability in cerebral small vessel disease in rats. Sci. Transl. Med. 2018. doi: 10.1126/scitranslmed.aam9507.
- Holley, JE et al. Increased blood vessel density and endothelial cell proliferation in multiple sclerosis cerebral white matter. Neurosci. Lett. 2010. doi: 10.1016/j.neulet.2009.12.059.
- Seabrook, TJ et al. Angiogenesis is present in experimental autoimmune encephalomyelitis and pro-angiogenic factors are increased in multiple sclerosis lesions. J. Neuroinflammation 2010. doi: 10.1186/1742-2094-7-95.
- Munji RN et al. Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module. Nat. Neurosci. 2019. doi: 10.1038/s41593-019-0497-x.
This project is centred on the neurodegenerative disease multiple sclerosis (MS). The student will be part of the MS Society UK-funded MS Centre and so will have much opportunity for public engagement through the centre and through the charity itself. AW is a MS Society Ambassador and a clinician, carrying out NHS clinics in the Anne Rowling Regenerative Neurology Clinic at Little France, with therefore access to around 3000 people with MS. This clinic is also involved in the current simvastatin trial in MS, MSSTAT2 (ClinicalTrials.gov Identifier: NCT03387670). The project is based in the CRM/IRR, which runs the science mentorship scheme at Castlebrae High School and is involved with teacher training as stem cell biology is part of the new science curriculum.
Researchers involved in this programme
Researchers involved in this programme are listed below, along with their current projects.
Our work involves a very rare cause of neurodevelopmental disorders. De novo heterozygous mutations in a gene called EEF1A2 can cause epilepsy, developmental delay and intellectual disability, but there are many distinct mutations that have only been seen in one individual. We are trying to: understand the mechanism by which these mutations perturb neuronal function, do genotype phenotype correlations, work on giving parents some prognostic information based on model organisms, and connect with families all over the world.
Therapeutic approaches and family engagement for a neurodevelopmental disorder: what does diagnosis of EEF1A2 really mean? (Primary supervisor)
We are trying to understand the mechanisms that make people desperately sick in sepsis, so that we can find new treatments. Our approach is based on these predictions:
- there is biological variation in the host response to injury;
- some of this variation is genetic;
- we can use this genetic variation to find new treatments.
Integrating genetic (GWAS) associations with Mendelian randomisation and functional genomics data may lead us to biological processes that might be amenable to treatment. We influenza as a model for the broader host response to critical injury.
None currently available through this programme.
In many tissues the most abundant immune cell is the macrophage. Macrophages are strategically positioned to capture and destroy microbial intruders, a role of particular importance at the mucosal barrier tissues, such as the gut and the lung which are major ports of entry for a multitude of pathogens. Aside from their innate immune functions, macrophages are essential for the clearance of dead cells and to support the stromal compartment through production of growth factors, as well as orchestrating tissue repair after injury or infection. Somewhat paradoxically, macrophages are implicated in many chronic pathologies where their behaviour is very different, and they appear to drive or perpetuate disease, for instance in inflammatory bowel disease or pulmonary fibrosis. This functional plasticity makes macrophages promising therapeutic targets but for this to be effective, the correct type of macrophage needs to be targeted. Thus, our work focusses on dissecting the heterogeneity of mucosal macrophages in different contexts, understanding the role of tissue resident versus recruited macrophages in disease and tissue repair, and ultimately on understanding the local environmental cues that imprint macrophage identity and function in health and how these change during disease.
Mitochondrial DAMPs triggering macrophage FPR1 ‘plaque’ receptor as a pathogenic factor in Crohn’s disease (Additional supervisor)
My lab researches the role of quantitative magnetic resonance imaging to investigate brain development of fetuses and neonates, biological and social factors that confer risk or resilience to perinatal brain injury, and the relationship between quantitative MR features and long-term functional outcome.
I am scientific director of the Jennifer Brown Research Laboratory, situated in the MRC Centre for Reproductive Health, and principal investigator of the Theirworld Edinburgh Birth Cohort, a research study aiming to improve the lives of babies born early and their families .
None currently available through this programme.
Respiratory infections are a leading cause of morbidity and mortality in children worldwide, and predispose to chronic lung problems. The respiratory and bacterial pathogens causing these infections are actually common colonizers of the upper respiratory tract as well, living mostly in full harmony with the host. The reason why in one child colonization with those pathogens is followed by disease, and in others not, is not fully understood. My research group has a major focus on investigating the physiology and pathophysiology of those infections from an ecological perspective, with a major focus on microbiome development early in life. Our ultimate goal is to design new treatment and preventive measures for respiratory infections in susceptible populations. To this purpose, the team uses a fully translational approach, combining epidemiological, molecular microbiological, immunological and systems biology approaches to answer their research questions. Moreover, we execute mechanistic studies in vitro and in vivo.
Translating microbiome knowledge into educational and preventive strategies (Primary supervisor)
Novel interventions for respiratory viral infections; targeting host defence peptides via pharmaceuticals and the microbiota (Additional supervisor)
The Anne Rowling Clinic delivers research and trials for people with neurodegenerative diseases including multiple sclerosis, motor neurone disease, Parkinson’s and cognitive disorders, as well as hosting NHS Lothian specialist clinics for these conditions. As the Clinic sits at the interface between laboratory research (stem cells, drug discovery), clinical research (trials, Scotland-wide disease registers) and clinical care, engagement with patients, families and the public is already firmly embedded. A project supervised by one of the Anne Rowling Clinic’s Investigators would provide plentiful rich opportunities for public engagement, for example via study focus groups, social science research, public events such as open evenings and patient:scientist exchanges, and digital communications.
None currently available through this programme.
The Davey Lab is interested in understanding the fundamental principles which govern pattern formation during embryonic development in order to improve both human and animal health. It is important to us that our work has a meaningful outcome for patients and we work with clinicians to decide which are the most important problems to tackle in our research. We examine the causes of differences of gene expression which lead to variations in phenotype using comparative anatomy, genetics, genomics and embryonic manipulation of avian species. The Davey Lab have expertise in gene expression analysis, particularly the molecular anatomy of the developing limb bud. With a framework of understanding the development of the limbs, the current work in the lab includes understanding the embryological origin of radial aplasia in humans, the evolution of limb pattern in birds, the function of the protein TALPID3 and the description and genetic basis of embryonic tempo.
The genetic and developmental causes of congenital forearm differences (Primary supervisor)
In an era of global anxiety about antibiotic resistance, Donald’s research is focused on developing new approaches to infectious and inflammatory diseases, with a specific interest in the roles of host defence peptides (antimicrobial peptides) as novel antimicrobials, their interplay with the microbiome, and their roles as modulators of inflammation and immunity, cell death and cell signalling. Current projects focus on pulmonary viral infections, barrier function in atopic dermatitis, and novel approaches to cancer immunotherapy. Donald is also Co-Director of this PhD Programme, leads Public Engagement for the Centre, and has developed a wide range of engagement initiatives, including the Supercytes resources.
Novel interventions for respiratory viral infections; targeting host defence peptides via pharmaceuticals and the microbiota (Primary supervisor)
Translating microbiome knowledge into educational and preventive strategies (Additional supervisor)
The Dockrell group study host-pathogen interactions primarily from the perspective of identifying microbicidal responses that maximise clearance of phagocytosed bacteria. The group is particularly interested in studying cell death paradigms and how these enhance pathogen clearance and influence the inflammatory response. A focus is understanding the basis of susceptibility and in understanding what constitutes an effective response and how diseases and pathogen attributes can subvert these and lead to poor outcomes.
Translating microbiome knowledge into educational and preventive strategies (Additional supervisor)
Investigating the antimicrobial and immunomodulatory functions of β-defensins for AMR therapeutic use (Additional supervisor)
My research focus is on the function of host defence peptides by studying the consequence of their dysfunction in vitro and in vivo. Current research projects include understanding their involvement in obesity and immunomodulation, and investigating their potential use as novel therapeutics to combat antimicrobial resistance.
Investigating the antimicrobial and immunomodulatory functions of β-defensins for AMR therapeutic use (Primary supervisor)
Radiotherapy is commonly used as a life-saving treatment for those with head and neck cancer. Although often effective at treating the cancer, a severe side-effect is damage to and scarring of healthy tissues within the field of irradiation. The salivary glands are often inadvertently irradiated and permanently damaged, resulting in a multitude of oral problems, such as difficulties eating and speaking and tooth decay, all of which can adversely affect a patient’s quality of life. Existing treatments concentrate only on short-term relief of such side-effects and no long-term restorative solutions exist. The current work in the Emmerson lab aims to develop strategies to manipulate niche signals to progenitor cells, inflammatory cells and senescent cells to ultimately promote endogenous tissue regeneration following injury or disease.
In addition, The Emmerson group is participating in a Sci-Art collaboration with local artist, Emily Fong. The aim of the project is to:
- Raise awareness of the prevalence of head and neck cancer and the long-term side-effects of radiotherapy
- Promote collaboration and discussion between patients and healthcare professionals throughout the entire process
- Engage with a public audience that may otherwise not be reached by conventional science communication methods
Preventing radiotherapy-induced salivary gland damage in head and neck cancer patients to improve quality of life (Primary supervisor)
View Elaine's profile and contact details
Our group is working to find a cure for the autoimmune rheumatic diseases, rheumatoid arthritis and SLE. We are using cutting edge technologies (including bulk RNA-Seq, Single cell sequencing, flow cytometry, histochemistry and cell culture) to dissect the pathogenic inflammatory mechanisms that drive human disease. Data from both these projects will be of great interest to the general public, patients that suffer from autoimmune diseases, funding bodies and government policy makers, creating opportunities to develop key public engagement skills.
None currently available through this programme.
We aim to understand the mechanisms by which apoptotic tumour cells condition the tumour micro-environment. Specifically, our work seeks to define:
- the mechanisms underlying the selective recruitment of mononuclear phagocytes to high-grade tumours in which cell death by apoptosis is frequent,
- the effects dying cells exert on their viable neighbours - including phagocytes and tumour cells - and the molecular players involved in promoting tumour establishment and growth, and
- novel anti-cancer therapeutic targets based around altering the innate immune responses against apoptotic cells.
None currently available through this programme.
I am interested in mechanisms that regulate arterial function and structure in health and disease, focussing on the role of the endothelium, new blood vessel formation (angiogenesis), and lesion formation (atherosclerosis, neointimal proliferation). Current research projects address: the potential use of cellular therapies to stimulate angiogenesis in ischaemic tissue; the influence of glucocorticoids on angiogenesis; the role of androgens in regulation of atherosclerosis and angiogenesis; and, the influence of the Wilms' Tumour suppressor on new blood vessel formation. My group uses a combination of in vitro, ex vivo and in vivo techniques to address these topics, with a strong focus on the use of novel imaging techniques to improve analysis.
None currently available through this programme.
My work is focused on understanding the complex pathogenic mechanisms involved in the abnormal gut inflammatory response and how to translate this into better treatments in Ulcerative Colitis (UC) and Crohn’s disease. Recently, I have successfully taken my basic scientific work to a national clinical trial to inhibit mitochondrial ROS in UC (MARVEL, 2019-2023) and large human focused studies into mitochondrial danger signalling (MUSIC and GI-DAMPs, 2019-2022). I lead the Edinburgh IBD Science with a strong portfolio of highly collaborative studies and we have a vibrant public involvement program.
Mitochondrial DAMPs triggering macrophage FPR1 ‘plaque’ receptor as a pathogenic factor in Crohn’s disease (Primary supervisor)
My research interests include endometriosis and ectopic pregnancy. Working closely with patients, discovery scientists and healthcare professionals, I use a bench-to-bedside approach to researching these common women’s health problems.
The role of immunometabolism in endometriosis (Primary supervisor)
The main focus of my research involves using the lungs of large animals as a model for pre-clinical development of respiratory gene therapy protocols, to evaluate both safety and efficacy of candidate gene transfer agents. We have expertise in non-viral and lentiviral vector based gene delivery in the lung using sheep and piglets. These studies have focussed primarily on gene therapy for Cystic Fibrosis, through the UK CF Gene Therapy Consortium (GTC), but more recently this has extended to other disease indications. A large Phase 2 clinical trial of repeated application of the non-viral gene therapy product to CF patients showed benefit of gene therapy versus placebo and the GTC are now looking to build on this through improvements to the non-viral product and the parallel development of a lentiviral product that performs significantly better in our preclinical models.
None currently available through this programme.
Our research focus is to investigate the regenerative properties of inflammation in the central nervous system in order to identify new therapeutic strategies for neurological disorders. In particular, we are interested in the health of the insulation surrounding nerve fibres, termed myelin, and how macrophages control myelin formation and regeneration in health and diseases such as cerebral palsy and multiple sclerosis. We use approaches like RNA sequencing, in vitro/ ex vivo/ and in vivo experimental modelling, live imaging and confocal imaging, nanoparticle drug-targeting, and human brain tissue analyses.
The first comprehensive assessment of human infant brain injury tissue (Primary supervisor)
My research interests include fertility preservation in the pre-pubertal testis and this focuses on developing strategies for removing and storing testis tissue from patients prior to potentially sterilizing treatments in order that germ cell development can be achieved using in-vitro or in-vivo techniques. We have recently become the first UK centre to establish a fertility preservation programme to store testicular tissue from young cancer patients prior to their treatment. This programme in males, combined with our well-established fertility preservation programme for females, has resulted in the establishment of a collaboration of scientists and clinicians working as part of the 'Edinburgh Fertility Preservation’ programme of which I am the lead for male fertility preservation. This unique collaboration combines clinical and laboratory research aimed at optimising fertility for children and young adults with cancer. We are also a full partner in the EU funded FP7 Marie Curie ITN entitled 'GROWSPERM' aimed at co-ordinating research into male fertility preservation for boys with cancer. We also receive funding for our male fertility preservation work from Children with Cancer UK.
The role of gankyrin as a fertility sparing therapy in children with cancer and men with testicular germ cell tumours (Primary supervisor)
I am interested in how our genes predipose us to, or protect us from, the adverse metabolic effects of the modern "obesogenic lifestyle". I believe understanding the intrinsic mechanisms that allow some people to remain lean, healthy and age successfully despite the "onslaught of plenty" will illuminate new therapeutic avenues for metabolic dysfunction and its associated diseases.
None currently available through this programme.
My lab's research focuses on the dynamics of epigenetic DNA methylation and histone modifications essential for early development, differentiation and cell fate reprogramming. These marks create an epigenetic ‘landscape’ that supports cell type specific gene regulatory networks but can also provide an epigenetic readout of exposures, ageing and other conditions. We study these epigenetic mechanisms in tissues, including cardiovascular development, disease and regeneration. We support and develop new ways of public engagement with research.
Diagnostic epigenetic markers for myocardial injury risk stratification (Primary supervisor)
Grounded in clinical practice, my over-arching interest is in applied health service research: addressing the T2, T3 and increasingly T4 translational gaps. I am interested in the development and evaluation of complex interventions and in the challenge of implementing effective interventions in routine practice. Current major projects focus on delivery of care within the ‘real-life’ clinical setting including implementing supported self-management, telehealthcare for people living with respiratory disease, and helping people with COPD and depression referred for pulmonary rehabilitation. I leads programme of work within the Asthma UK Centre for Applied Research (AUKCAR) and the NIHR Global Health Research Unit on Respiratory Health (RESPIRE), and co-lead the PG training platform of the AUKCAR.
None currently available through this programme.
Our research uses cutting-edge technologies and analytical approaches in genomics, transcriptomics, and cell biology to trace the causal links from DNA change to disease. This research is thus positioned at the intersection between disease genomics, computational biology and experimental determination of molecular mechanism. Finally, we are interested in ME/CFS genetics: how its findings influence patients and the public, and how people with lived experience of ME/CFS influence scientists.
Myalgic encephalomyelitis (ME): Genetics, truth and reconciliation (Primary supervisor)
My research focuses on a life-course approach to prevention of non-communicable diseases. Key examples a) using healthcare-record data-linkage and cohort studies to document the consequences of a mother’s health in pregnancy on the health of next and future generations; b) identifying underpinning mechanisms through experimental medicine studies embedded within clinical practice; and c) testing novel interventions to improve pregnancy outcomes in clinical trials.
Data-driven innovation for gestational diabetes (Primary supervisor)
My research focuses on cognitive function including memory and executive functions, mental health, and academic learning in children and young people (CYP) with neurodevelopmental disorders. This includes CYP with ADHD, DCD/dyspraxia, Autism Spectrum Disorder and those with undiagnosed learning difficulties/affected by early adversity. In addition to profiling research, I am involved in the development of clinical screening measures and interventions relating to these areas of functioning. She also researches the cognitive factors underlying mental health in the general population both in child and adult samples.
Understanding the transition from childhood to adolescence and mental health in girls with neurodevelopmental disorders (Primary supervisor)
The Applied Bioinformatics of Cancer research group focuses on the integration of high-throughput genomic data with patient stratification, relevance of cancer models and analysis of patient-matched sequential samples to understand the molecular dynamics and consequences of treatment and other interventions.
None currently available through this programme.
The Sloan lab is interested in antiviral innate immunity, in particular the phenomena of cell autonomous innate immunity, wherein antiviral factors inside cells directly control and subvert viral replication. We are interested in how cell autonomous innate immunity may be important in disease susceptibility, or may be harnessed therapeutically to control viral infection. To do this we try and understand the molecular and cellular biology of candidate antiviral factors and how viruses respond to avoid them, particularly in the context of HIV infection. However, we are similarly interested in cellular endogenous retroelements and emerging virus infections.
None currently available through this programme.
My research focuses on the pregnancy complications preterm birth and stillbirth. Each year more than 15 million babies are born preterm, and 2.5 million are stillborn. My aim is to develop better ways of predicting and diagnosing these pregnancy complications and improve treatment strategies for mothers and babies. I lead the Consortium for the Study of Pregnancy Treatments (Co_OPT), which is a cross-disciplinary collaboration to investigate the effects of treatments given in pregnancy. Parental engagement is key to this research, with a parental advisory board representing parents from six countries. Public engagement activities include a collaboration with Dirty Market Theatre Company to develop an interactive performance game on decision making about pregnancy treatments.
Risk prediction in pregnancy (Primary supervisor)
My team develops fluorescent probes that light up in specific groups of immune cells that are directly related to how our body responds to inflammatory diseases and cancer. The signals that are produced by the probes allow us to take real-time images from live cells, tissues or intact organisms in high-resolution microscopes. This approach helps us understand how different types of immune cells influence the progression of diseases, either negatively or positively, and develop better technologies to spot diseases earlier and to treat them more effectively.
Novel interventions for respiratory viral infections; targeting host defence peptides via pharmaceuticals and the microbiota (Additional supervisor)
Our research looks at defining the role of oxygen sensing and metabolism in myeloid cell mediated inflammation and host pathogen responses and the therapeutic potential of manipulating these pathways in inflammatory lung disease.
None currently available through this programme.
The Williams group is interested in neuropathology of the brain, and in particular the white matter where most oligodendrocytes reside. These can be affected in many neurodegenerative diseases, and we are particularly interested in how these interact with nerves and other cells in diseases such as multiple sclerosis and cerebral small vessel disease. We work with human tissue and preclinical models of disease to unpick the pathophysiology of disease and to manipulate it to promote repair.
The role of brain endothelial cells in multiple sclerosis (Primary supervisor)
The first comprehensive assessment of human infant brain injury tissue (Additional supervisor)
If you have any questions about the programme, please don't hesitate to contact us.