Fixed-term

 Prof Rob Falconer,  Dr Steven Shnyder Application Deadline: Applications accepted all year round Details Polysialic acid plays an essential role in neuronal development, but by adulthood is absent from the human body. Its biosynthesis is regulated by two polysialyltransferases. Polysialic acid is aberrantly re-expressed on the surface of many tumours, where it plays a key role in diseases progression and metastasis. It is therefore an attractive anti-cancer target [1]. The Institute of Cancer Therapeutics, at the University of Bradford, is focused on the development of novel polysialyltransferase inhibitors, using computational chemistry to aid compound design. We have developed assays to assess compound inhibition [2] and have utilized tool compounds to show the potential of the approach [3]. We additionally have explored the role of polySia expression in hypoxia, a characteristic common to solid tumours [4,5]. The wider project benefits from funding from programme funding from Yorkshire Cancer Research and more recently from the Wellcome Trust. The student will join a successful, motivated multidisciplinary team with expertise in medicinal chemistry, pharmacology, immunohistochemistry and drug analysis. This project will focus on the biological evaluation of potential polysialyltransferase inhibitors, utilising in vitro assays to assess compound inhibition, and techniques to assess effects of compounds on cell adhesion, migration, and invasion. How to apply Formal applications can be submitted via the University of Bradford web site. Applicants should register an account, select ‘Postgraduate Research’ as the course type and use the keywords ‘cancer therapeutics’. Please include the project title on the Research Proposal section; applicants are not required to supply a research proposal for this project. Informal enquiries are also welcome. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded project; applicants will be expected to pay their own fees or have access to suitable third-party funding. In addition to the university’s standard tuition fees, bench fees of £10,000 per year also apply to this project. References 1. Current Cancer Drug Targets, 2012, 12, 925-9392. Analyst, 2016, 141, 5849-58563. PLoS ONE, 2013, 8, e733664. Scientific Reports, 2016, 6, 330265. ChemBioChem, 2017, 18, 1332-1337 At least 2:1 honours degree in a pharmacy, biochemistry or pharmacology-related subject. An MSc in any of these areas is an advantage. For full details of our entry requirements, please visit our website. Apply Now

 Dr Vibhu Jha,  Prof Rob Falconer Application Deadline: Applications accepted all year round Details Polysialic acid (polySia) is a carbohydrate polymer important for embryonic development. PolySia is absent in healthy adult tissues whereas overexpressed in several tumours. The high expression of PolySia-NCAM (neuronal cell adhesion molecule) is strongly associated with poor clinical prognosis and several cancers such as lung cancer, pancreatic cancer, neuroblastoma, and gliomas. The synthesis of polySia is mediated by two polysialyltransferases (polySTs): ST8SiaII and ST8SiaIV. In particular, ST8SiaII is of great importance due to its high expression in several tumours which can be thus targeted for selective inhibition, further presenting a new therapeutic opportunity to treat metastatic cancer. Our previous work has demonstrated the druggability of ST8SiaII. We already have established in vitro and in vivo models for the screening of new compounds. The project is driven by advanced in silico modelling as following: 1. Structure-based design Techniques such as homology modelling, high throughput virtual screening, molecular docking (HTVS), binding free energy calculations, prediction of pharmacokinetic properties and molecular dynamics simulations will be employed to screen and prioritize drug-like small molecules that could bind to the substrate binding site of ST8SiaII (relative to in-house inhibitor CMP). The promising hit compounds will be purchased/synthesized and will be tested experimentally. 2. Machine learning Multiple machine learning models will be developed based on the chemical information of the existing ST8SiaII inhibitors. The best model will be combined with HTVS to score and screen potential hit compounds that could bind selectively to ST8SiaII over other isoforms such as ST3Gal-III, ST3GaI-IV and ST6Gal-I. 3. Development of protein – protein interaction inhibitors ST8SiaII forms key protein-protein interactions with NCAM which are crucial for polysialylation. A consensus protein – protein docking approach will be implemented to develop ST8SiaII – NCAM interaction models, followed by oligopeptide docking and construction of pharmacophore models to eventually identify new peptides/compounds disrupting the protein – protein interaction. How to apply Formal applications can be made through the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keywords ‘cancer therapeutics’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee of £5000 per year applies to this project, in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support. References 1. Jha V, Holmelin FL, Eriksson LA. Binding Analysis and Structure-Based Design of Tricyclic Coumarin-Derived MTHFD2 Inhibitors as Anticancer Agents: Insights from ComputationalModeling. ACS Omega. 2023 Apr 12;8(16):14440-14458. https://doi.org/10.1021/acsomega.2c080252. Jha V, Biagi M, Spinelli V, Di Stefano M, Macchia M, Minutolo F, Granchi C, Poli G, Tuccinardi T. Discovery of Monoacylglycerol Lipase (MAGL) Inhibitors Based on a Pharmacophore-Guided Virtual Screening Study. Molecules. 2020 Dec 26;26(1):78. https://doi.org/10.3390/molecules260100783. Falconer RA, Errington RJ, Shnyder SD, Smith PJ, Patterson LH. Polysialyltransferase: a new target in metastatic cancer. Curr Cancer Drug Targets. 2012 Oct;12(8):925-39. http://dx.doi.org/10.2174/1568009128032512254. Al-Saraireh YM, Sutherland M, Springett BR, Freiberger F, Ribeiro Morais G, Loadman PM, Errington RJ, Smith PJ, Fukuda M, Gerardy-Schahn R, Patterson LH, Shnyder SD, FalconerRA. Pharmacological inhibition of polysialyltransferase ST8SiaII modulates tumour cell migration. PLoS One. 2013 Aug 9;8(8):e73366. doi: 10.1371/journal.pone.0073366.https://doi.org/10.1371/journal.pone.00733665. Close BE, Mendiratta SS, Geiger KM, Broom LJ, Ho LL, Colley KJ. The minimal structural domains required for neural cell adhesion molecule polysialylation by PST/ST8Sia IV and ST8SiaII/ST8Sia II. J Biol Chem. 2003 Aug 15;278(33):30796-805. doi: 10.1074/jbc.M305390200. https://doi.org/10.1074/jbc.M305390200 Apply Now

 Dr Munir Hussain,  Dr Talat Nasim,  Prof Mark Boyett Application Deadline: Applications accepted all year round Details Evaluation of human-induced pluripotent stem cell-derived cardiac myocytes (hiPSC-CMs) for cardiotoxicity testing Potentially fatal cardiac arrhythmias such as Torsades des Pointes (TdP) are linked to adverse side-effects of drugs intended as potential treatments for a variety of clinical disorders. Drugs that, unintentionally, affect ion channels can increase or decrease the cardiac action potential duration, depending on their effect. For example, drugs that inhibit K+ channels can prolong the action potential by delaying repolarisation, which is manifested as the long QT interval in the electrocardiogram and is associated with an increased risk of arrhythmias such as TdP. Potential new medicines must therefore be evaluated for the likelihood of cardiotoxic effects and be screened out as early as possible in the drug development process. hiPSC-CMs are widely used for cardiotoxicity testing as a desirable alternative to expression systems as well as animal cardiac cells (Zhao et al 2018). However, whether hiPSC-CMs contain ion channels that represent the characteristics of adult human cardiac myocytes has not yet been fully established. This project therefore seeks to characterise the electrophysiological properties of the ion channels expressed in hiPSC-CMs to evaluate their potential significance for cardiotoxicity testing. Experiments to be performed will characterise the inhibitory effects of a wide selection of drugs on ionic currents in hiPSC-CMs (e.g. INa, INaL, ICaL, Ito, IKr, IKs and IK1) as listed in CiPA (Crumb et al 2016). The proposed experiments will investigate the activation and inactivation characteristics of these (and other) ionic currents, as well as their sensitivity to the selected drugs relevant to these channels. In addition to these ionic current measurements, voltage- and calcium-sensitive dyes will also be used to measure action potentials and intracellular calcium transients, respectively. Results from these measurements will be compared to those where hiPSC-CMs have been co-cultured with other cell types (e.g. fibroblasts and endothelial cells) to form organoids, as well as to ionic currents recorded in cultured expression systems and isolated guinea-pig cardiomyocytes (Chorvatova et al 2004). Results from this study will help develop an improved understanding of how better and safer therapeutic approaches can be developed for the treatment of human disease in the future. How to apply Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keywords ‘biomedical science’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee of £15,000 per year applies, in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support. References Chorvatova A, Snowdon R, Hart G, Hussain M. (2004). Effects of pressure overload-induced hypertrophy on TTX-sensitive inward currents in guinea pig left ventricle. Mol Cell Biochem.Jun;261(1-2):217-26.Crumb, WJ, Vicente, J., Johannesen l and Strauss DG. (2016). An evaluation of 30 clinical drugs against the comprehensive in vitro proarrhythmia assay (CiPA) proposed ion channel panel. J. Pharmacological and Toxicological Methods. 81:251-262Zhao Z, Lan H, El-Battrawy I, Li X, Buljubasic F, Sattler K, Yücel G, Lang S, Tiburcy M, Zimmermann WH, Cyganek L, Utikal J, Wieland T, Borggrefe M, Zhou XB, Akin I. (2018). Ion Channel Expression and Characterization in Human Induced Pluripotent Stem Cell-derived cardiomyocytes. Stem Cells Int. 8: 6067096. Apply Now

 Dr Sneha Swaroop Application Deadline: Applications accepted all year round Details Endocrine-disrupting compounds (EDCs) are a group of chemicals that can alter the normal functioning of the body’s hormonal system and can have harmful effects. EDCs can also be found in everyday products like food preservatives, plastic packaging, cosmetics, personal care products, fragrances, and pharmaceutical drugs. There is growing evidence suggesting that EDCs entering human breast tissues from various sources is one of the important contributors to the globally increasing risk of breast cancer. To understand this link better, we will study the effect of certain newly identified EDCs on cells in the breast including both normal and stem cells (SCs). SCs are a small group of unspecialized cells residing in the breast which plays a crucial role in inducing breast cancer. Our initial studies used a series of online tools to analyze the health and safety-related data of the EDCs used in food contact materials and have identified five new potentially harmful EDCs that could increase the risk of cancer. In the present study will study the impact of the identified EDCs on breast cells by evaluating their ability to increase cell growth and activate or inhibit the production of reproductive hormones such as oestrogens using commercially available kits. Furthermore, the effect of the selected EDCs on the functioning of normal breast stem cells will be assessed using specific assays to understand their role in causing cancer. Finally, we will use advanced models (body-on-chip) that can mimic a human body to confirm our findings in a more realistic environment. In summary, the proposal aims to understand how novels EDCs from food contact materials can affect breast cells and stem cells to increase the risk of cancer. By understanding this, we can develop new ways to prevent breast cancer along with raising awareness that can empower individuals to make informed choices. We are looking for an enthusiastic student interested in exploring the role of novel EDCs in breast tumorigenesis. The successful candidate will have the opportunity to develop their research skills in techniques such as: Culture of different normal breast cell lines and generating CSC-enriched spheroid cultures. Perform techniques such as cell proliferation assays, receptor binding assay, transcriptional activation assay and steroidogenesis. Evaluating the effect of EDCs on normal stem cells by assessing stem cell functional assays such as a) single cell colony formation assay; Aldeflour assay and epigenetic analysis. Grow multiple immortalised human cell lines from different tissues on multi organ chambers to create a “body-on-chip” (BOC) model. Entry requirements Applicants are expected to hold (or to soon achieve) a minimum upper second class undergraduate honours degree (or equivalent) in biosciences including Biochemistry, Biology, Biomedical Sciences or related discipline. A Masters degree in a relevant subject and/or experience in laboratory-based research are also desirable. In addition to the academic requirements for the project the following skills and behaviours would be advantageous: A curiosity to expand your knowledge of business practices and how research insights can be translated into consumer applications An appreciation of the benefits of stakeholder management The ability to tailor information to the needs of different audiences How to apply Formal applications can be made through the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keywords ‘cancer therapeutics’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee may apply to this project, in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support. Apply Now

 Dr Sneha Swaroop Application Deadline: Applications accepted all year round Details Epithelial ovarian cancer (EOC) is the leading cause of mortality in women due to gynaecological cancers. High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of patients with EOC. Currently, in advanced HGSOC, chemotherapy with Carboplatin and Taxol is the standard treatment following surgery. More recently, chemotherapy in combination with bevacizumab or PARP inhibitors have shown a modest improvement in survival. However, the 5-year overall survival (OS) of advanced HGSOC remains at 30-45%. This is due to recurrence of disease and one of the reasons is the presence of stem cells which are resistant to conventional chemotherapy. Tumour-initiating stem cells or cancer stem cells (CSCs) cells are subset of cells that give rise to a heterogeneous population of cells similar in composition to the tumour of origin and are maintained by regulatory embryonic pathways such as Wnt/β-catenin, Notch, and Hedgehog. Our previous study has identified that the hedgehog signalling (Hh) is essential for the regulation of ovarian CSCs and blocking this pathway using small molecule inhibitors can abrogate CSCs. Interestingly, inhibiting Hh also reduced the expression of certain genes known as interferon stimulated genes (ISGs) which are usually turned on in response to a viral infection. This project will extend our research and further investigate the importance of ISGs in ovarian CSCs which can lead to the development of effective and selective treatment strategies against EOC stem-cells. This is an exciting and important research line to be pursued as ISGs could be a potential target that can be probed to effectively eradicate CSCs and achieve long term remission in ovarian cancer patients suffering from recurrent and resistant disease worldwide. We are looking for an enthusiastic student interested in exploring how ISGs influence cancer stemness. The successful candidate will have the opportunity to develop their research skills in techniques such as: Culture of different ovarian cell lines and generating CSC-enriched spheroid cultures. Validating the expression profile of selected ISGs in 2D and 3D models of ovarian cancer cells using techniques including qPCR, Western blot, and immunohistochemistry. Evaluating the influence of ISG expression on cancer stemness using stem cell functional assays such as single cell colony formation assay; Aldeflour assay; side population assay and the expression of CSC-specific transcription factors (Oct3/4, Sox2, Nanog and Nestin) using quantitative PCR. How to apply Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keywords ‘cancer therapeutics’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee may apply in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support. References Sneha S. et al Cell Oncol (Dordr) 2020 43(4):601-616   Apply Now

 Dr Talat Nasim,  Dr Mojgan Najafzadeh Application Deadline: Applications accepted all year round Details Myelodysplastic syndromes (MDS) are a type of blood cancer where the patients do not have enough healthy blood cells. It is the most common adult myeloid malignancy in the UK and has been estimated that around 8,000 and 40,000 new cases are diagnosed each year in the UK and USA, respectively.[1] MDS are a heterogeneous group of clonal haematopoietic stem cell disorders characterized by peripheral blood cytopenias and progenitor expansion. Approximately 30% of patients will transform to secondary acute myeloid leukemia (AML) which has a poor prognosis.[2] There is no cure for MDS. Current management therapies include allogeneic haematopoietic cell transplantation, DNA methytransferase inhibitors (DNMTI), also termed hypomethylating agents (HMA), azacitidine or decitabine. Most MDS patients are not eligible for cell transplantation whilst azacitidine has been shown to modestly improve survival compared to standard care.[3] Once patients stop responding to HMA therapy, however, outcomes are dismal, with a median survival of less than six months.[4] Using unbiased sequencing approaches, we (in collaboration with Washington University, USA) and others have identified mutations in 4 genes including SF3B1, SRSF2, U2AF1, and ZRSR2, which are involved in pre-mRNA splicing in ~50% of patients with MDS, making this cellular pathway the most commonly mutated in MDS.[5-8] Current therapies were established prior to the fact that MDS has substantial splicing abnormalities and hence there is a need to identify novel therapeutic intervention targeting the over-active spliceosomal genes. We have developed high-throughput splicing assays [9-11] [12], screened thousands of natural products and established drugs and identified novel hits. The major objectives of this project are to (a) investigate how overactive splicing contributes to disease pathogenesis and (b) determine whether natural products may provide therapeutic intervention. The project will introduce the student to the broader areas of molecular genetics, biochemistry, drug discovery, pharmacology and translational medicine. The research activities will be undertaken at the School of Pharmacy and Medical Sciences, University of Bradford. The studies will be performed in the recently renovated laboratories provided with state of the art equipments including high-throughput fluorescence and luminescence plate readers, QPCR machines, gel doc systems and modern tissue culture facilities. The research sits in the context of a highly active research environment at the University of Bradford. How to apply Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keyword ‘pharmacy’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded project; applicants will be expected to pay their own fees or have access to suitable third-party funding, such as the Doctoral Loan from Student Finance. In addition to the university’s standard tuition fees, bench fees of £5000 or £10000 per year may also apply to this project. References based algorithm: high number of uncaptured cases by cancer registries. Blood, 2011. 117(26): p. 7121-5.2. Greenberg, P.L., et al., Revised international prognostic scoring system for myelodysplastic syndromes. Blood, 2012. 120(12): p. 2454-65.3. Silverman, L.R., et al., Randomized controlled trial of azacitidine in patients with the myelodysplastic syndrome: a study of the cancer and leukemia group B. J Clin Oncol, 2002. 20(10): p. 2429-40.4. Jabbour, E., et al., Outcome of patients with myelodysplastic syndrome after failure of decitabine therapy. Cancer, 2010. 116(16): p. 3830-4.5. Yoshida, K., et al., Frequent pathway mutations of splicing machinery in myelodysplasia. Nature, 2011. 478(7367): p. 64-9.6. Graubert, T.A., et al., Recurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes. Nat Genet, 2011. 44(1): p. 53-7.7. Papaemmanuil, E., et al., Somatic SF3B1 mutation in myelodysplasia with ring sideroblasts. N Engl J Med, 2011. 365(15): p. 1384-95.8. Visconte, V., et al., SF3B1, a splicing factor is frequently mutated in refractory anemia with ring sideroblasts. Leukemia, 2012. 26(3): p. 542-5.9. Nasim, M.T., et al., HnRNP G and Tra2beta: opposite effects on splicing matched by antagonism in RNA binding. Hum Mol Genet, 2003. 12(11): p. 1337-48.10. Nasim, M.T., H.M. Chowdhury, and I.C. Eperon, A double reporter assay for detecting changes in the ratio of spliced and unspliced mRNA in mammalian cells. Nucleic Acids Res, 2002. 30(20): p. e109.11. Nasim, M.T. and I.C. Eperon, A double-reporter splicing assay for determining splicing efficiency in mammalian cells. Nat Protoc, 2006. 1(2): p. 1022-8.12. Hu, J., et al., AKAP95 regulates splicing through scaffolding RNAs and RNA processing factors. Nat Commun, 2016. 7: p. 13347. Apply Now

 Dr Talat Nasim,  Prof Colin Wright Application Deadline: Applications accepted all year round Details Pulmonary arterial hypertension (PAH) is a devastating cardiovascular disorder which, if left untreated, leads to heart failure and death. There is currently no cure for this disease. The major aims of the current treatments are to improve symptoms and increase exercise tolerance. We have identified genetic defects in bone morphogenetic protein type II receptor (BMPR2), SMAD1, SMAD4 and SMAD9 genes in patients suffering from this disorder. We have found that these mutations not only reduce BMP signalling, but also activate the transforming growth factor β (TGFβ) signalling pathway. These dysfunctions signalling events lead cells found in the pulmonary arterial wall to multiply too quickly. This means that the pulmonary arterial wall gets thicker, restricting blood flow and increasing blood pressure in the pulmonary artery. We have found that chemicals that either inhibit the TGFβ signaling or promote the BMP signalling reduce abnormal proliferation and show beneficial effects in animal models (rat and mouse) of the disease. Taken together, these observations suggest that compounds that inhibit the overactive TGFβ or promote the BMP pathway may provide a therapeutic effect on people suffering from PAH. Funding received from the Medical Research Council, Royal Society, Sasakawa Foundation, Commonwealth Scholarship Commission, National Institute of Health Research and a number of venture capital companies enabled us to investigate the consequences of gene defects and screened thousands of compounds including established drugs and natural products. The prospective student will investigate how dysfunctional BMP and TGFβ signalling pathways contribute to disease pathogenesis and identify novel therapeutic intervention using natural products. The project will introduce the student to the broader areas of molecular genetics, biochemistry, drug discovery, pharmacology and translational medicine. The research activities will be undertaken at the School of Pharmacy and Medical Sciences, University of Bradford. The studies will be performed in the recently renovated laboratories provided with state of the art equipments including high-throughput fluorescence and luminescence plate readers, QPCR machines, gel doc systems and modern tissue culture facilities. The research sits in the context of a highly active research environment at the University of Bradford. How to apply Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keyword ‘pharmacy’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee applies, in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support.   Apply Now

 Dr Afeesh Rajan Unnithan Application Deadline: Applications accepted all year round Details Are you passionate about cutting-edge biomedical research that can change lives? This PhD project offers an exciting opportunity to develop a next-generation self-powered wound dressing that uses electrical stimulation to heal diabetic foot ulcers (DFUs),one of the most challenging complications of diabetes. DFUs are slow-healing wounds that can lead to serious infections and amputations. Current treatments often fail to speed up healing, leaving patients at risk. This project aims to revolutionise wound care by developing a smart, piezoelectric nanofibre dressing that generates electrical signals simply from body movement. These tiny electrical pulses mimic the body’s natural healing signals, stimulating immune cells to switch from an inflammatory state to a regenerative one and encouraging fibroblasts to rebuild damaged tissue. As a PhD researcher, you will: Develop and optimise advanced piezoelectric nanoparticles and nanofibres using cutting-edge electrospinning techniques. Investigate how piezoelectrical stimulation reprogrammes immune cells and enhances skin regeneration in lab-based studies. Test the dressing’s effectiveness in preclinical models, bringing it closer to real-world application. This interdisciplinary project sits at the intersection of biomaterials, mechanobiology, and regenerative medicine, offering hands-on experience in innovative healthcare technologies. Supported by expert supervisors and state-of-the-art research facilities at the University of Bradford, you will be at the forefront of developing game-changing therapies that could significantly improve DFU treatment and patient quality of life. If you’re driven by innovation and eager to make an impact in biomedical science, apply now to join this pioneering research and help shape the future of wound healing! How to apply Formal applications can be made through the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the type of course and then use the keyword ‘pharmacy’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee of £10,000 per year, over three years also applies to this project, in addition to the tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support. Apply Now

 Dr Kirsten Riches-Suman,  Dr Ethan Perkins Application Deadline: Applications accepted all year round Details Cardiovascular disease is a leading cause of morbidity and mortality across the globe. Disorders of the blood vessels, such as atherosclerosis, hypertension, aneurysm or stroke are responsible for substantial health and social care costs and the mechanisms that lead to these disorders are still incompletely understood, hence there is an urgent need to create laboratory models of these disorders that can help drive the understanding of disease mechanisms and the design of new and effective therapeutics. Blood vessels are comprised of three layers; a monolayer of endothelial cells (ECs) termed the intima which lines the inner surface of all blood vessels, a thicker medial layer comprised of smooth muscle cells (SMC) and an outer layer of connective tissue and fibroblasts termed the adventitia. These layers all need to work in harmony with each other, with extensive cross-communication between EC and SMC, in order to work efficiently. The majority of research to date on mechanisms underpinning EC and SMC dysfunction have used in vitro 2D models, where the cells are grown in a monolayer in isolation. As these do not allow for communication between cell types and their growth conditions are not comparable to the in vivo structural environment, translation of findings into clinical understanding can be problematic. Therefore, the aim of this project is to design and evaluate advanced 3D cell models, incorporating communication between different cell types, to generate an easy to use model that mimics the in vivo scenario more closely. How to apply Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the course and then use the keywords ‘biomedical science’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. Bench fees may apply to this project, in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support. Apply Now

 Dr Kirsten Riches-Suman,  Dr Jurgen Muller Application Deadline: Applications accepted all year round Details Radiotherapy is a common treatment for cancer, and is used in over 70% of breast cancer patients. However, radiotherapy is associated with longer term vascular damage including atherosclerosis development and fibrosis. Clinically, this can be observed in patients undergoing deep inferior epigastric perforator (DIEP) reconstruction following mastectomy and radiotherapy. In this procedure, skin, fat and blood vessels from the lower abdomen are used to create a reconstructed breast, with the blood vessels being intricately woven into the breast site to maintain reconstructed tissue viability. This includes perforator blood vessels, which are those that link the larger arteries and veins with the microvascular network in the skin. During surgery, the blood vessels in the irradiated tissue are seen to be more delicate than the blood vessels from the non-irradiated epigastric flap, with the layers of the blood vessels having a tendency to separate from each other with a fibrotic texture. The cellular and molecular causes of these clinical observations are unknown. The clinical issue of post-radiotherapy vascular damage is poorly understood, with most studies using animal models or using in vitro radiation of isolated cells. In contrast, this project will use tissue from patients who have undergone radiotherapy prior to DIEP reconstruction to provide a comprehensive assessment of the effect of targeted radiotherapy on the vasculature of breast cancer patients. It will identify whether perforator smooth muscle cells can be used as a proxy for smooth muscle cell alterations in deeper macrovessels. It will use primary cell culture, molecular biology approaches (qPCR, siRNA) and immunoflurescent methods. Furthermore, the use of tissue from multiple patient donors will allow us to assess interpatient variability, which is important for translation of basic research findings into the clinic. How to apply Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account, select ‘Postgraduate Research’ as the course and then use the keywords ‘biomedical science’. Applicants should then specify the project title in the ‘Research Proposal’ section. About the University of Bradford Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities. Positive Action Statement At the University of Bradford our vision is a world of inclusion and equality of opportunity, where people want to, and can, make a difference. We place equality and diversity, inclusion, and a commitment to social mobility at the centre of our mission and ethos. In working to make a difference we are committed to addressing systemic inequality and disadvantages experienced by Black, Asian and Minority Ethnic staff and students. Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level.  These are lawful measures designed to address systemic and structural issues which result in the under-representation of Black, Asian, and Minority Ethnic students in PGR studies. Funding Notes This is a self-funded PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. Bench fees may apply to this project, in addition to tuition fees. UK students may be able to apply for a Doctoral Loan from Student Finance for financial support. Apply Now