Fixed-term

Details Human cytomegalovirus (HCMV) is a ubiquitous virus with an adult seroprevalence worldwide of 86%. In most immunocompetent individuals infection is asymptomatic but the virus establishes a life-long infection with periodic reactivation and asymptomatic shedding. If a pregnant woman acquires the infection or a previous infection reactivates during pregnancy the virus can pass through the placenta to infect the fetus. Such congenitally acquired HCMV (cHCMV) is the most common congenital infection having an overall incidence of 0.64% of all live births, with considerably higher rates in some geographical regions. There are three possible outcomes of a congenital infection: severe disease evident at birth with a poor prognosis (10-15% of infants); asymptomatic infection (85-90% of affected infants); development of late sequelae, notably sensorineural hearing loss, among 10-15% of apparently asymptomatic babies. There is currently no means to predict which of the asymptomatic babies will go on to develop sequelae. This makes a universal newborn screening programme for cHCMV difficult to justify on ethical grounds as most babies who would test positive in such a programme would remain healthy. A further barrier to implementing a universal screening programme is however, a lack of any consensus with regards to an appropriate sample type. The “gold standard” sample for diagnosing a congenital cytomegalovirus infection in a newborn infant is urine as generally viral concentrations are high in this sample. However, urine is a difficult specimen to collect from a baby and is impractical for the routine collection from all newborns. Other possible samples are saliva or blood (collected as a dried blood spot on filter paper). There are a number of studies that have evaluated saliva or DBS as a specimen for cHCMV but the data obtained shows wide variation in sensitivity and specificity of both methods. There are a number of possible reasons for this including variations in sample volume collected, variation in recovery of nucleic acid from the sample prior to molecular testing and variation in methodologies used to carry out the sample preparation and testing. In this project we will determine the optimal sample and method for detection of cytomegalovirus in newborn infants with the aim of fulfilling the criteria required to justify implementation of universal screening for cHCMV Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in a related area/subject. Candidates with prior experience in cell culture, viral assay or molecular virology are encouraged to apply, but for good candidates with other relevant experience training will be provided in these techniques. Eligibility  Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD PhD Medical Virology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/

Details Oesophageal adenocarcinoma (OAC) is a deadly disease with poor survival statistics, is one of the highest incidence cancer types and is growing in prevalence, particularly in the developing world. A major reason for this, is the lack of treatment options, due mainly to our lack of knowledge of molecular targets that arise from a detailed molecular understanding of the disease. Ove the past decade, our own work has helped to bridge this gap by investigating the gene regulatory mechanisms that lead to and maintain the cancer state in OAC (eg see Rogerson et al., 2019; Ogden et al., 2022; Ahmed et al., 2023; Yang et al., 2024). However, numerous questions remain. For example, although we have discovered that the precursor metaplastic state, Barrett’s oesophagus, shares gene regulatory networks with early developmental populations (Baker et al., 2023), how this is reconfigured in OAC progression and then reutilised following therapeutic drug treatment is poorly understood. Furthermore, there are numerous uncharacterised gene regulatory proteins beyond these networks that have been implicated in OAC, and we have identified dozens of potential new players from a recent CRISPR viability screen. Projects are available to dissect and understand the gene regulatory networks that are operational during OAC progression, how these relate to developmental events and how they are repurposed to survive therapeutic insults. We are interested in both transcription factors and chromatin associated proteins and how they work in these contexts. A combination of detailed molecular and genome-wide approaches will be used, supplemented by computational methodologies. Recognising the complexity and heterogeneity of OAC, we will also incorporate single cell technologies to understand the gene regulatory networks that are operational in different subpopulations typically found in a patient. These studies will generate more effective therapeutic opportunities to combat this deadly disease. Eligibility  Candidates are expected to hold (or be about to obtain) a minimum of a high scoring upper second class honours degree (or equivalent) in a related area / subject. Candidates with experience in genome-wide approaches (experimental and computational) and with an interest in understanding how gene regulatory networks are reprogrammed in disease states such as cancer are encouraged to apply. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD Molecular Biology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/ References Rogerson C., Britton, E., Withey, S., Hanley, N., Ang, Y. and Sharrocks, A.D. (2019) Identification of a primitive intestinal transcription factor network shared between oesophageal adenocarcinoma and its pre-cancerous precursor state. Genome Research. 29(5):723-736. Ogden, S., Carys, K., Ahmed, I., Bruce, J. and Sharrocks, A.D. (2022) Regulatory chromatin rewiring promotes metabolic switching during adaptation to oncogenic receptor tyrosine kinase inhibition. Oncogene. 41(43):4808-4822. Ahmed, I., Yang, S-H., Ogden, S., Zhang, W., Li, Y., the OCCAMS consortium, Sharrocks, A.D. (2023) eRNA profiling uncovers the enhancer landscape of oesophageal adenocarcinoma and reveals new deregulated pathways. eLife. 12:e80840. Yang, S-H., Ahmed, I., Li, Y., Bleaney, C.W., Sharrocks, A.D. (2024) Massively Parallel Reporter Assays identify enhancer elements in Oesophageal Adenocarcinoma. NAR Cancer. 6(4):zcae041. Baker SM, Mullan A, Jennings RE, Piper-Hanley K, Ang Y, Palles C, Hanley NA, Sharrocks AD. The metaplastic precursor state to oesophageal adenocarcinoma represents reversion to a transient epithelial cell state in the developing oesophagus. 2024. BioRkiv. doi: https://doi.org/10.1101/2024.07.25.605105.

Details Healthy skin depends on strong adhesion between the cells of the upper layers of epidermis and the underlying dermis. When these attachment fails, as in trauma, chronic wounds or inherited blistering disorders, patients suffer from recurrent infections, impaired healing, and pain. The restoration process involves wound matrix, and epidermal adhesion to it, which doesn’t happen in large-area wounds, resulting in ulcers or extensive scars. MicroRNAs regulate skin adhesion by binding mRNAs, lowering expression of proteins. Our preliminary work identifies microRNA-29 (miR-29) as a key regulator of cell adhesion in healthy skin and reveals function of miR-29 in healing wounds. High levels of miR-29 weaken attachment of keratinocytes, while inhibition of miR-29 strengthens adhesion, enhances fibroblast matrix deposition, and prolongs keratinocyte growth. During wound repair, genetic deletion of miR-29 creates a pro-healing matrix with enhanced vascularization and faster formation of neo-epidermis – a new layer of the skin that ensures scar-free wound closure. We demonstrated that levels of miR-29 temporarily decreased in wounds, allowing enhanced pro-adhesive protein synthesis. In later phase of skin repair, miR-29 expression is restored to the upper layers of the skin and the dermis, ensuring suppression of pro-fibrotic proteins. This suggests that miR-29 acts as a molecular switch between regeneration and tissue failure, offering a promising therapeutic target. In this project, you will: 1. Elucidate the mechanisms through which miR-29 represses adhesion of epithelial keratinocytes to the matrix. Determine how miR-29 regulates cell-matrix adhesion via integrin receptors by use of atomic force measurements (AFM), which will define the activation states of the receptors and how this is dependent on the presence of miR-29. 2. Determine how miR-29 regulates keratinocyte adhesion via the deposition of the matrix by dermal fibroblasts. You will culture human dermal fibroblasts transfected with miR-29 and will separate the deposited matrix to determine proteins upregulated as a result of miR-29 inhibition in an unbiased way using proteomics. Eligibility Applicants are expected to hold a minimum upper second-class undergraduate honours degree (or equivalent) in Biology. Research experience (e.g., Masters) in applying theoretical and practical methods to analyse and interpret the data generated by modern biology is desirable. Candidates with a minimum upper second-class undergraduate honours degree (or equivalent) in Biology/Biomedical Sciences will be also considered given the evidence of sufficient skills for the project. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD Cell Biology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 2 (med) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/

Details Turtles are unique among vertebrates living their lives inside a box – their shell – which influences every aspect of their biology. Turtles are vital to the health of marine ecosystems and we aim to collect data on the biomechanics and energetics of their movements at a critical juncture in their lives, when nesting, to better understand how these keystone species influence the structure and dynamics of their environment. Sea turtle populations have suffered substantial declines linked to anthropogenic pressures, with 85% of extant species now at population levels well below their historical abundance levels. Human activities threaten sea turtle populations at a multitude of levels from the impact of human encroachment for the development of ocean view land, to increased mortality associated with fishing bycatch, direct harvesting of turtles for food and the wide-ranging effects of human-driven climate change. Changes in global temperature and ocean warming are particularly pertinent for sea turtles given their temperature dependent sex determination, which will influence their genetic health. Monitoring reproductive activity and assessing the overall health of populations of these species is necessary for developing effective conservation strategies. Globally, six of the seven sea turtle species are listed as being threatened or endangered meaning increasing our knowledge of the factors influencing the success of their nesting biology and the genetic health of their populations is becoming ever more critical. Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in Biology or Zoology. Candidates with experience in whole animal biology or with an interest in biomechanics, animal physiology and field work are encouraged to apply. Eligibility  Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD Environmental Biology Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 2 (med) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/ References Ewart HE, Tickle PG, Nudds RL, Sellers WI, Crossley II, DA & Codd JR (2022) Mediterranean spur-thighed tortoise (Testudo graeca) have optimal speeds at which they can minimise the metabolic cost of transport. Biology, 11, 1052: 1-13. (https://doi.org/10.3390/biology/11071052) IF 5.1, Rank Q1 Multidisciplinary. Costello, L, Garcia-Perraga, D, Crespo-Picazo, JL, Codd, JR, Shiels, HA & Joyce W. (2022) Absence of atrial smooth muscle in the heart of the loggerhead sea turtle (Caretta caretta): a re-evaluation of its role in diving physiology. J. Exp. Biol. 225, jeb244864. (doi:10.1242/jeb.244864) Ewart HE, Tickle PG, Sellers, WI, Lambertz, M, Crossley II DA & Codd JR (2022) The metabolic cost of turning right side up in the Mediterranean spur-thighed tortoise (Testudo graeca). Nature Sci. Reports. 12:431. (https://doi.org/10./1038/s41598-021-04273-w). IF 5.133, Rank 17/72 Multidisciplinary Ruhr IM, Rose KAR, Sellers WI, Crossley II DA & Codd JR (2021) Turning turtle: scaling relationships and self-righting ability in Chelydra serpentina. Proc. R. Soc. B. 288: No 1946 20210213 (https://doi.org/10.1098/rspb.2021.0213). IF 5.349 Rank 13/93 Biology. Sellers WI, Rose KAR, Crossley II DA & Codd JR (2020) Inferring cost of transport from whole-body kinematics in three sympatric turtle species with different locomotor habits. Comp. Biochem. Physiol. A. 247: 110739 (https://doi.org/10.1016/j.cbpa.2020.110739). IF 2.069 Rank 185/266 Biochemistry & Molecular Biology.

Details The role mitochondria play in disease is ever expanding. Due to their fundamental role in ATP production and cell death, amongst others, there is intense investigation to uncover the roles they play in disease and uncovering novel pathways that can be targeted therapeutically. We are interested in the role of mitochondrial reactive oxygen species and how they may be drivers of disease. We have shown that mitochondrial reactive species, particularly driven by reverse electron transport at mitochondrial complex I leads to ischaemia/reperfusion injury in heart attack and ischaemic stroke, as well as being important in neurodegeneration, inflammation, cancer, diabetes and aging. In this project, we aim to understand the mechanisms behind mitochondrial reactive oxygen species production in different models of disease to understand the unifying conditions required to drive this. Furthermore, by understanding these conditions, we aim to understand novel therapeutic targets as well as the potential to repurpose approved drugs to counteract aberrant mitochondrial reactive oxygen species production for therapeutic benefit. Training – extensive training will be provided throughout this PhD on a range of experimental techniques in multiple disciplines. This will include techniques in molecular and cell biology, biochemistry, cell culture and in vivo work. As well as technical skills, presentation skills, public speaking, data analysis, data presentation and academic writing skills training will all be extensively provided. Eligibility Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD xxxx Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/ References F. Mcewan, M.K. Harte et al; (2025) Association between redox dysregulation and vulnerability to cognitive deficits induced by maternal immune activation. Translational Psychiatry. Lee, J. J., Prag, H. A. et al; (2025) Local arterial administration of acidified malonate as an adjunct therapy to mechanical thrombectomy in ischemic stroke. Cardiovascular research. Casey, A. M., Ryan, D. G., Prag, H. A et al; (2025) Pro-inflammatory macrophages produce mitochondria-derived superoxide by reverse electron transport at complex I that regulates IL-1β release during NLRP3 inflammasome activation. Nature Metabolism. Prag, H. A., Murphy, M. P. & Krieg, T.; (2023) Preventing mitochondrial reverse electron transport as a strategy for cardioprotection. Basic Research in Cardiology Prag, H. A. et al; (2022) Ischemia-Selective Cardioprotection by Malonate for Ischemia/Reperfusion Injury. Circulation research

Details Stroke is a major cause of death and disability, costing over £6 billion per annum in the UK. A key event during stroke pathogenesis is inflammation regulated by the cytokine interleukin-1 (IL-1) that contributes to brain injury and poor outcome. The IL-1 family of cytokine is composed of two agonists, IL-1alpha (IL-1α) and IL-1beta (IL-1β) and one functional type 1 receptor, but the precise contribution of each IL-1 family members to post-stroke inflammation is unknown. We have recently demonstrated, using new conditional IL-1 genetic mouse models developed by us, that microglial-specific IL-1α is a key regulator of vascular inflammation and repair after stroke. Senescence is an irreversible replicative-arrest state of the cells, leading to dysfunction of surrounding cells, accompanied by expression of pro-inflammatory cytokines such as IL-1α, IL-1β, IL-6, and IL-8 (referred to as senescence-associated secretory phenotype, SASPs). Senescent cells during ageing promotes tissue inflammation and dysfunction, and is an essential contributor to the progression of age-associated diseases. Importantly, senescence of vascular-related cells contributes to blood–brain barrier dysfunction, a key hallmark of stroke pathogenesis and a risk factor in stroke. The main aim of the project is to investigate new mechanisms of IL-1α-regulated cerebrovascular senescence in stroke, and how those mechanisms could be a risk factor for stroke and key contributors to poor cerebrovascular repair and poor outcomes in aged stroke patients. The project will be conducted within the Brain Inflammation Group, School of Biological Sciences, University of Manchester. The group uses an interdisciplinary approach to understand mechanisms of neuroinflammation in brain disease and is a world leader in the field. The project will use a very large range of cutting-edge state-of-the-art models of brain injury, analytical techniques from molecular/cellular biology to powerful brain imaging techniques and behavioural tests. Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in Neuroscience or Biomedical Sciences. Research experience in cell cultures, in vivo animal models of disease and basic analytical techniques is desirable. Eligibility  Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD Neuroscience Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/ References – Barrington J, Rivers-Auty J, Strangward P, Tamburrano S, Lénárt N, Swanton T, Lemarchand E, Parry-Jones AR, Dénes Á, Brough D, Allan SM. Interleukin-1 regulates myeloid cell trafficking and cerebral blood flow following intracerebral haemorrhage. Dis Model Mech. 2025 Oct 1;18 – Lemarchand E, Grayston A, Wong R, Rogers M, Ouvrier B, Llewellyn B, Webb F, Lénárt N, Dénes Á, Brough D, Allan SM, Bix GJ, Pinteaux E. Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but may regulate neurorepair processes after experimental ischemic stroke. J Cereb Blood Flow Metab. 2025 Aug;45(8):1479-1492. – Wong R, Smith CJ, Allan SM, Pinteaux E. Preconditioning with interleukin-1 alpha is required for the neuroprotective properties of mesenchymal stem cells after ischemic stroke in mice. J Cereb Blood Flow Metab. 2023 Dec;43(12):2040-2048. – Taylor JL, Pritchard HAT, Walsh KR, Strangward P, White C, Hill-Eubanks D, Alakrawi M, Hennig GW, Allan SM, Nelson MT, Greenstein AS. Functionally linked potassium channel activity in cerebral endothelial and smooth muscle cells is compromised in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2022 Jun 28;119(26):e2204581119. – South K, Saleh O, Lemarchand E, Coutts G, Smith CJ, Schiessl I, Allan SM. Robust thrombolytic and anti-inflammatory action of a constitutively active ADAMTS13 variant in murine stroke models. Blood. 2022 Mar 10;139(10):1575-1587.

Details Stroke is a leading cause of death and disability worldwide but with limited therapies, thus new therapeutic strategies are urgently needed. Inflammation after stroke is associated with poor outcome and is thus an attractive therapeutic target. A key mediator of inflammation is the cytokine interleukin-1 (IL-1), and blocking IL-1 actions have shown promise for acute neuroprotection and recovery in preclinical stroke models, and is currently tested in stroke patients. A potential new approach in stroke therapy is the targeted application of human mesenchymal (stromal) stem cells (MSCs) that can exert potent anti-inflammatory, neuroprotective and regenerative actions. In vitro pre-treatment of MSCs by specific culture conditions and/or biological agents (also known as “preconditioning” or “priming”) can improve the survival, engraftment, immunosuppressive and paracrine properties of MSCs, therefore enhancing their regenerative capacity. The effect of MSC priming with inflammatory mediators and hypoxia is unexplored, but our previous research found that MSCs can be primed by IL-1 and hypoxia to exert potent anti-inflammatory and neurotrophic effects in vitro. We have recently tested the beneficial effects of IL-1 preconditioning of MSCs in clinically-relevant animal stroke models for their potential use in future stroke therapies. We now aim to understand the mechanisms underlying those effects, and this project will study the effects of IL-1/hypoxia primed MSCs on neuroprotection in experimental stroke models, as well as neurones, endothelial cells and astrocytes injury after oxygen and glucose deprivation (OGD), with the ultimate aim to explore the potential clinical application of IL-1 primed MSCs in stroke. Candidates are expected to hold (or be about to obtain) a minimum 2:1 Bachelors Degree with Honours (or equivalent) in Neuroscience or Biomedical Sciences. Research experience in cell cultures, in vivo animal models of disease and basic analytical techniques is desirable. Eligibility  Applicants must have obtained or be about to obtain a minimum Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in a relevant discipline. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD Neuroscience Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 3 (high) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/ References – Salaudeen MA, Allan S, Pinteaux E. Hypoxia and interleukin-1-primed mesenchymal stem/stromal cells as novel therapy for stroke. Hum Cell. 2024 Jan;37(1):154-166. – Wong R, Smith CJ, Allan SM, Pinteaux E. Preconditioning with interleukin-1 alpha is required for the neuroprotective properties of mesenchymal stem cells after ischemic stroke in mice. J Cereb Blood Flow Metab. 2023 Dec;43(12):2040-2048. – Cunningham CJ, Wong R, Barrington J, Tamburrano S, Pinteaux E, Allan SM. Systemic conditioned medium treatment from interleukin-1 primed mesenchymal stem cells promotes recovery after stroke. Stem Cell Res Ther. 2020 Jan 21;11(1):32. -Redondo-Castro E, Cunningham C, Miller J, Martuscelli L, Aoulad-Ali S, Rothwell NJ, Kielty CM, Allan SM, Pinteaux E. Interleukin-1 primes human mesenchymal stem cells towards an anti-inflammatory and pro-trophic phenotype in vitro. Stem Cell Res Ther. 2017 Apr 17;8(1):79.

Details Bacteria colonize skin but in general, do not form biofilms when the skin is intact; however, bacteria do form biofilms in wounds which delays healing. The presence of biofilms can reduce the effectiveness of antibacterial treatments, and the skin and wound environments, and microbiota crosstalk which in turn may influence the composition of biofilms. Biofilms, heterogenous bacterial communities adhering to a surface, are surrounded by a complex matrix composed of exopolysaccharides, proteins, and extracellular DNA. This structure not only upholds the rigid architecture, but additionally protects from physiological and chemical stresses such as evasion of the hosts immune system and shear forces. The components of the biofilms exhibit viscoelastic properties meaning they can display both fluid and elastic rheological characteristics, which are important to understand factors affecting the penetration of drugs in biofilms. So far, studies of biofilms in wounds have typically relied on in vivo animal systems or simple 2D in vitro models; thus reliable in vitro models to study biofilms are lacking; their development would be in line with the 3Rs (replacement, reduction and refinement) principle of in vivo research. Here we propose to developing in vitro models based on keratinocytes and dermal fibroblasts cultured on supported membranes and assess the development and resistance to treatment of biofilms within novel in vitro models. Key objectives: – To develop coculture of keratinocytes and dermal fibroblasts on transwell to understand the formation of tight cell cultures and then develop coculture of keratinocytes and dermal fibroblasts on Ibidi µ-Slide Membrane ibiPore Flow chambers, – To define appropriate conditions for the formation of biofilms of specific bacteria. – To characterise the biofilm structural and antimicrobial tolerance properties using methods that include microrheology, fluorescence and confocal microscopy. – To assess changes in the biofilm structural properties following treatment. Eligibility Applicants are expected to hold, or about to obtain, a minimum upper second-class undergraduate degree (or equivalent) in microbiology, (bio)chemical engineering, chemistry, biochemistry, biophysics, pharmaceutical sciences or related subject. A Master’s degree in a relevant subject and/or experience in microbiology. (bio)chemical engineering, chemistry, biochemistry, biophysics or related subject is desirable but not necessary. They are also expected to have a strong will to learn different scientific aspects. Before you Apply Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application. How to Apply To be considered for this project you MUST submit a formal online application form – on the application form select PhD Pharmaceutical Science Programme. Full details on how to apply can be found on the Website: How to apply for postgraduate research at The University of Manchester If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk Equality, Diversity and Inclusion Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website: Equality, diversity and inclusion (EDI | Postgraduate Research | Biology, Medicine and Health | University of Manchester Funding Notes Applications are invited from self-funded students. This project has a Band 2 (med) fee. Details of our different fee bands can be found on our website https://www.bmh.manchester.ac.uk/study/research/fees/ References Buzza et al. (2023) Microbiology Spectrum DOI: 10.1128/spectrum.02527-22 HC Flemming et al., Nat Rev Microbiol (2023), DOI: 10.1038/s41579-022-00791-0 Hoffman et al., Biomedicines (2023) DOI : 10.3390/biomedicines11041056 Chen et al. Nature (2018) DOI:10.1038/nature25177

Details Background: Genome-Wide Association Studies (GWAS) were successful in identifying 100s of genetic variants associated with autoimmune disease susceptibility. However, the value of Polygenic Risk Scores (PRS) for clinical medicine is limited. When considered in aggregate, genetic variants identified so far explain only a small proportion of genetic liability to disease (missing heritability), because of methodological limitations. Also, traditionally, GWAS were performed in individuals of a single ethnicity (or ancestry). The impact of ancestry-specific associations on molecular and cellular pathways are unknown. Therefore, complex disease genetics faces today three major challenges: 1) the development of new artificial intelligence (AI)-based methodologies to fully capture the genetic architecture of autoimmune disease; 2) explain disease heterogeneity by translating long lists of susceptibility polymorphisms into cell type-specific molecular pathways to define disease endotypes for precision medicine; 3) understand how genetic differences between ancestries impact on cell type-specific molecular pathways, disease aetiology and outcome. Research question: To identify ancestry-specific cell subsets and their intracellular pathways under the control of genetic polymorphisms conferring susceptibility to autoimmune diseases. Methods and objectives: Objective 1 – comparative performance of AI algorithms over traditional statistical approaches across ethnicities: Recent large GWAS have identified genetic susceptibility polymorphisms associated with rheumatoid arthritis (RA) [1], Psoriatic Arthritis (PsA) [2] and myositis [3]. We will use cutting-edge artificial intelligence (AI) network algorithms [4,5] to identify sets of polymorphisms associated with each disease. The performance of various AI tools over standard statistical approaches will be assessed by their capacity to identify known variants. New variants will be validated in external datasets (collaborators). Analysis will be conducted in different ethnic groups. Objective 2, mapping genetic polymorphisms to genes, pathways and cell types across ethnicities: Known and newly identified susceptibility polymorphisms will be mapped to genes, genes to pathways, and pathways to cell types, using publicly available resources (including expression/splicing/protein quantitative trait loci, transcription factor binding, chromatin conformation, epigenetic marks). We will assess if and which cellular pathways are ancestry-specific. Objective 3, experimental in vitro validation of cellular quantitative trait loci (optional): Experimental validation in the wet lab will be performed by testing the association of a pathway-specific PRS with specific cellular functions (i.e. a T-cell receptor signalling pathway PRS will be tested for its association with IL-17 cytokine expression in T cells). A set of > 100 healthy volunteers peripheral blood mononuclear cells is available for this project (including genome-wide genotypes). Specific pathways will be stimulated in vitro (for example anti-CD3/CD8 beads for TCR signalling) and effector function (i.e. cytokine production) will be quantified by multiparameter flow cytometry. Training opportunities: This is an exciting opportunity for a highly motivated student to join a vibrant and dynamic research environment and a great training opportunity in AI, bioinformatics, statistical genetics. This project also offers the possibility for interested applicants to be trained in wet lab techniques. The supervisory team offers expertise for 1-to-1 training in all areas, in addition to regular University training programmes. Entry Requirements Applicants are expected to hold (or about to obtain) a minimum upper second-class undergraduate honours degree (or equivalent) in bioinformatics, information technology, informatics, biostatistics or relevant subject area. Applicants are expected to have a strong interest and background in command line programming and bioinformatics. No prior knowledge in immunology/rheumatology is required (although it will be an advantage). No prior skills in flow cytometry or wet lab is required (but would be an advantage for candidates choosing the optional experimental validation step (Objective 3). Application Guidance Candidates must contact the primary supervisor before applying to discuss their interest in the project and assess their suitability. Apply directly via this link: https://tinyurl.com/ycweuusx or on the online application portal, select Bioinformatics PhD as the programme of study. Please ensure that your application includes all required supporting documents: Curriculum Vitae (CV) Supporting Statement Academic Certificates and Transcripts Incomplete or late applications will not be considered. Further details are available on our website. Funding Notes This 4 year PhD project is for self funded students. At Manchester we offer a range of scholarships, studentships and awards at university, faculty and department level, to support both UK and overseas postgraduate researchers applying for competition and self-funded projects. For more information, visit our funding page or search our funding database for specific scholarships, studentships and awards you may be eligible for. References: [1] Ishigaki K, Sakaue S, Terao C, […], Viatte S, […], Bowes J, et al. Multi-ancestry genome-wide association analyses identify novel genetic mechanisms in rheumatoid arthritis. Nat Genet. 2022 Nov;54(11):1640-1651. [2] Bowes J, et al. Dense genotyping of immune-related susceptibility loci reveals new insights into the genetics of psoriatic arthritis. Nat Commun. 2015 Feb 5;6:6046. [3] Zhu C, […], Lamb JA, Amos CI; Myositis Genetics Consortium. Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses. Arthritis Rheumatol. 2025 Jun;77(6):750-764. [4] Jalali-Najafabadi F, […], Bowes J; BADBIR Study Group; BSTOP Study Group. Application of information theoretic feature selection and machine learning methods for the development of genetic risk prediction models. Sci Rep. 2021 Dec 2;11(1):23335. [5] Bracher-Smith M, Melograna F, Ulm B, et al. Machine learning in Alzheimer’s disease genetics. Nat Commun. 2025 Jul 22;16(1):6726.