Fixed-term

Details Natural products have emerged as a key standard in novel and safe delivery of anticancer bioactive compounds. Apart from their ease of administration and delivery, natural/phytochemicals still face several hurdles, due to their physiochemical and pharmacokinetic properties. Nowadays, nanotechnology has been widely proposed to deliver herbal drugs, due to its drug delivery system which might potentiate the pharmacological profile of phytochemicals. In the last decade, several studies have been focused on targeting synthetic drugs using polymers. Several research groups reported the semi-synthetic derivative of natural products with polymers, however, there is a need for research to be done with isolated natural compounds. Polymeric conjugation/encapsulation with poor-bioavailable phytopharmaceuticals might increase their bioavailability and thereby may decrease the dose frequency leading to improved patient compliance. As classical prodrugs, they can accelerate the process of endocytosis to cross the cell membrane and reach their intracellular targets. This is because of their enhanced EPR effect, which can enhance the accumulation of tumour mass. The terminal groups are amenable to specific functionalities and allow molecules to be attached to a phytochemical moiety, resulting in targeted specific, and controlled drug delivery. With this immense potential and possibilities, the present research work is proposed to overcome the hurdle of natural product delivery using nano formulations. The properties of the nano formulation would be combined with the advantages of nano formulation for targeted delivery of the natural anticancer bioactive compounds. Objectives To perform pre-formulation studies of the selected natural bioactive compounds. To optimise nano-formulation for effective delivery. To perform the characterization of developed formulation using various analytical techniques and stability studies. To carry out in vivo and/or in vitro anticancer studies using suitable models for the evaluation of developed nano formulation (s). 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 ‘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. 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. References 1. Chaturvedi S, Naseem Z, El-Khamisy SF, Wahajuddin M (2022) Nanomedicines targeting the Inflammasome as a promising therapeutic approach for cell senescence. Semin Cancer Biol. 86(2):46-53. PMID: 36030027 2. Singh SK, Rashid M, Bhalala K, Malik Y, Chaturvedi S, Raju KSR, Sultana N, Mitra K, Gayen JR, Wahajuddin M (2021) A Novel Nanosized Phospholipid Complex of Biochanin A for Improving Oral Bioavailability: Preparation and In-vitro/In-vivo Characterizations. Journal of Drug Delivery Science and Technology. 61: 102254 3. Garg A, Tomar DS, Bhalala K, Wahajuddin M (2020) Development and investigation of Artemether loaded binary solid lipid nanoparticles: Physicochemical characterization and in-situ single-pass intestinal permeability. Journal of Drug Delivery Science and Technology. 60: 102072. 4. Chaturvedi S, Malik MY, Rashid M, Singh SK, Tiwari V, Gupta P, Shukla S, Singh S and Wahajuddin M (2020) Mechanistic exploration of quercetin against metronidazole induced neurotoxicity in rats: possible role of nitric oxide isoforms and inflammatory cytokines. NeuroToxicology. 79:1-10. PMID: 32151614 5. Taneja I, Raghuvanshi A, Raju KSR, Awasthi P, Rashid M, Singh S, Goel A, Singh SP, Wahajuddin M (2020) Bioavailability, tissue distribution and excretion studies of a potential anti-osteoporotic agent, medicarpin, in female rats using validated LC-MS/MS method. J Pharm. Biomed. Anal. 180: 112978. PMID 31855725 6. Raju KSR, Rashid M, Gundeti M, Taneja I, Malik MY, Singh SK, Chaturvedi S, Challagundla M, Singh SP, Gayen JR, Wahajuddin M (2019) LC-ESI-MS/MS method for the simultaneous determination of Isoformononetin, daidzein, and equol in rat plasma: Application to a preclinical pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci. 1129:121776. PMID: 31629309 7. Chaturvedi S, Rashid M, Malik Y, Agarwal A, Singh SK, Gayen JR and Wahajuddin M (2019). Neuropharmacokinetics: A bridging tool between CNS Drug Development and Therapeutic Outcome, Drug Discovery Today, 24 (5): 1166-1175. PMID: 30898661 8. Rashid M, Malik Y, Singh SK. Chaturvedi S, Gayen JR and Wahajuddin M (2019). Bioavailability enhancement of poorly soluble drugs: The Holy Grail in pharma industry, Current Pharmaceutical Design; 25 (9):987-1020. PMID: 30706801 9. Rashid M, Singh SK, Malik MY, Jahan S, Chaturvedi S, Taneja I, Raju KS, Zaiba Naseem, Gayen JR, Wahajuddin M§. Development and validation of UPLC-MS/MS assay for quantification of Cladrin: Absolute bioavailability and dose proportionality study in rats. Journal of Pharmaceutical and Biomedical Analysis, 152, 289-297 PMID: 29454264 10. K Shahad ali, Garg Anuj§, Wahajuddin (2018) Development and evaluation of Chrysin-phospholipid complex loaded solid lipid nanoparticles-storage stability and in vitro anti-cancer activity. Journal of Microencapsulation. 2018 Aug 18; 35(6):600-17 Apply Now

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

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. 81:251-262 Zhao 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

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

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

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 Computational Modeling. ACS Omega. 2023 Apr 12;8(16):14440-14458. https://doi.org/10.1021/acsomega.2c08025 2. 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/molecules26010078 3. 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/10.2174/156800912803251225 4. 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, Falconer RA. 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.0073366 5. 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

Details Pulmonary arterial hypertension (PAH) is an incurable and devastating disease and death occurs within 2.5 years of diagnosis. Sustained elevation of the pulmonary arterial pressure (PAP) above 25mm Hg at rest or 30mm Hg during exercise with a normal pulmonary capillary wedge pressure (≤15mm Hg) in the absence of underlying heart, lung or thrombo-occlusive disorders is clinically known as PAH. At present, there is no cure for this disorder. Current therapies for PAH are very costly with an estimated annual treatment and care expenditure for each PAH patient varying substantially between medications, with £39,000 for iloprost, £23,500 for bosentan, £6,000 for sildenafil and £120,000 for treprostinil with combination therapy potentially reaching an average of a £200-300,000 per year. Therefore, there is an urgent need to develop effective medicines to treat PAH. We have showed that mutations in a specific gene (called BMPR2) can increase a person’s risk of getting PAH and identified factors that regulate the BMPRII-mediated signalling defects in PAH. In this project we will investigate the underlying mechanisms of disease pathogenesis and identify novel therapies for PAH. How to apply Formal applications can be submitted 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 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 may also apply to this project. References 1. N. Sharmin, C. Nganwuchu and M T Nasim*. Targeting the TGFβ signalling pathway for resolution of pulmonary arterial hypertension. Trends in Pharmacological Sciences: May 2021. 2. G. Durham, J. Williams, M. T. Nasim and T. Palmer. New mechanisms to target JAK-STAT signalling in disease. Trends in Pharmacological Sciences 40: 298-308, 2019. 3. H. M. Chowdhury, N. Sharmin, M. Baran, L. Long, N.W. Morrell, R. C. Trembath and M. T. Nasim*. BMPRII deficiency impairs apoptosis via the BMPRII-ALK1-BclXL-mediated pathway in pulmonary arterial hypertension (PAH) Human Molecular Genetics, 28:2161-2173, 2019 4. H. M. Chowdhury, M. A. Sidiqui, S. Kanneganti, N. Sharmin and M. T. Nasim*. Aminoglycosides-mediated promotion of translation readthrough occurs through a non-stochastic mechanism that completes with translation termination. Hum Mol Genet. 27: 373-384, 2018. 5. T. Ogo, H.M. Chowdhury, R. Randall, L. Long, J. Yang, R. Schumerly, N.W. Morrell, R.C. Trembath and M.T. Nasim*. Inhibition of the overactive TGFβ signalling by prostacyclin analogues in pulmonary arterial hypertension (PAH). American Journal of Respiratory Cell and Molecular Biology, 48(6):733-41, 2013. 6. M.A Siddiqui, T. Ogo and M.T. Nasim*. Pulmonary Arterial Hypertension: molecular genetic basis and emerging treatments (Invited review). AKMC J 3(2): 30-33, 2012 7. M.T. Nasim*, T. Ogo, H.M. Chowdhury, L. Zhao, C.N. Chen, C. Rhodes, and R.C. Trembath. BMPR-II deficiency elicits anti-apoptotic and pro-proliferative responses through the activation of TGFβ-TAK1-MAPK pathways in PAH. Human Mol Genetics (21):2548-58, 2012. 8. M T. Nasim, T. Ogo, M. Ahmed, R. Randall, H.M. Chowdhury, K. Snape, T. Bradshaw, F. Soubrier, I. Jackson, G. Lord, M. Humbert, N. Morrell, R. C. Trembath and R. Machado,. Molecular genetic characterization of Smad signalling molecules in pulmonary arterial hypertension (PAH). Human Mutation 12:1385-89, 2011. 9. M.T. Nasim*, A.G. Ghouri, B.P. Patel, V. James, N. Rudarakanchana, N. Morrell and R.C. Trembath. Stoichiometric imbalance in the receptor complex contributes to the dysfunctional BMPR-II mediated signalling in pulmonary arterial hypertension. Hum Mol Genet (11):1683-94, 2008. 10. M.T. Nasim* and R.C. Trembath. A dual-light reporter system to determine protein-protein interaction into mammalian cells. Nucleic Acids Res. 33(7): e66 (8 pages), 2005. Apply Now

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 established drugs and novel compounds. The prospective student will further investigate the underlying mechanisms of disease pathogenesis and identify novel therapeutic intervention. The project will introduce the student to the broader areas of molecular genetics, biochemistry, drug discovery 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 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 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

Details Chronic wounds, particularly diabetic foot ulcers, affect millions of patients worldwide and remain one of the most difficult clinical challenges in healthcare. Current wound dressings mainly protect the wound but do little to actively stimulate tissue repair. This PhD project will develop next-generation smart hydrogels capable of generating therapeutic electrical signals from natural body movement. By integrating piezoelectric nanomaterials into soft hydrogel systems, the project aims to create self-powered wound dressings that convert mechanical energy (such as pressure or movement) into electrical cues that stimulate tissue regeneration. These innovative biomaterials could help enhance cell migration, improve blood vessel formation, and accelerate healing in chronic wounds without requiring external power sources or devices. The successful candidate will work at the interface of biomaterials science, nanotechnology, and regenerative medicine, gaining hands-on experience in hydrogel engineering, nanomaterial synthesis, materials characterisation, and cell biology. This interdisciplinary project offers an exciting opportunity to contribute to the development of smart biomaterials that actively interact with the body to promote healing. The outcomes of this research could lead to new therapeutic strategies for chronic wound care and other regenerative medicine applications. The PhD student will join a collaborative research environment focused on advanced biomaterials and biomedical innovation, with opportunities to develop strong research skills and contribute to high-impact scientific publications. 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. References 1. Afeesh Rajan Unnithan, Vignesh Krishnamoorthi Kaliannagounder, Nagamalleswara Rao Alluri, Chan Hee Park, Pandiyarasan Veluswamy, Arathyram Ramachandra Kurup Sasikala, Design and Application of Piezoelectric Conductive Smart Scaffold for Non-invasive Neural Tissue Regeneration via Custom-made In vitro Mechano-Stimulator, Advanced NanoBiomed Research., 5: 2500058, 2025). 2. Arathyram Ramachandra Kurup Sasikala, Vignesh Krishnamoorthi Kaliannagounder, Nagamalleswara Rao Alluri, Sang-Jae Kim, Bishnu Kumar Shrestha, Hanene Ali-Boucetta, Chan Hee Park, Afeesh Rajan Unnithan, Remotely Actuated Self-Powered Multifunctional Piezomagnetic Nanoparticles: Proof of Concept Study for the Post-Surgical Osteosarcoma Theranogeneration, Nano Energy, 96, 107134, 2022, Senior author) 3. Sharifiaghdam, M.; Shaabani, E.; Faridi-Majidi, R.; De Smedt, S. C.; Braeckmans, K.; Fraire, J. C., Macrophages as a therapeutic target to promote diabetic wound healing. Mol Ther 2022, 30 (9), 2891-2908. 4. Mackenzie, P. Diabetes Footcare Project 1: Pathway Development; NHS UK, 2017. 5. Kerr, M.; Barron, E.; Chadwick, P.; Evans, T.; Kong, W. M.; Rayman, G.; Sutton-Smith, M.; Todd, G.; Young, B.; Jeffcoate, W. J., The cost of diabetic foot ulcers and amputations to the National Health Service in England. Diabetic Med 2019, 36 (8), 995-1002. 6. Xiong, Y.; Feng, Q.; Lu, L.; Zha, K. K.; Yu, T.; Lin, Z.; Hu, Y. Q.; Panayi, A. C.; Nosrati-Ziahmagi, V.; Chu, X. Y.; Chen, L.; Shahbazi, M. A.; Mi, B. B.; Liu, G. H., Immunomodulatory Hydrogels: Advanced Regenerative Tools for Diabetic Foot Ulcer. Adv Funct Mater 2023, 33 (10). 7. Hao Wu, H. D., Zhen Tang, Yu Chen, Yichao Liu, Mo Wang, Xinghui Wei,; Ning Wang, S. B., Dongmei Yu, Zhigang Wu, Zhenda Yang, Xiaokang Li; Zheng Guo, L. S., Electrical stimulation of piezoelectric BaTiO3 coated Ti6Al4V scaffolds promotes anti-inflammatory polarization of macrophages and bone repair via MAPK/JNK inhibition and OXPHOS activation. Biomaterials 2023, 293, 121990. 8. Koel, G.; Houghton, P. E., Electrostimulation: Current Status, Strength of Evidence Guidelines, and Meta-Analysis. Adv Wound Care (New Rochelle) 2014, 3 (2), 118-126. 9. Oliveira, K. M. C.; Barker, J. H.; Berezikov, E.; Pindur, L.; Kynigopoulos, S.; Eischen-Loges, M.; Han,Z.; Bhavsar, M. B.; Henrich, D.; Leppik, L., Electrical stimulation shifts healing/scarring towards regeneration in a rat limb amputation model. Sci Rep-Uk 2019, 9. 10. Chen, S.; Zhu, P.; Mao, L. J.; Wu, W. C.; Lin, H.; Xu, D. L.; Lu, X. Y.; Shi, J. L., Piezocatalytic Medicine: An Emerging Frontier using Piezoelectric Materials for Biomedical Applications. Adv Mater 2023, 35 (25). 11. Dai, J. J.; Shao, J.; Zhang, Y.; Hang, R. Y.; Yao, X. H.; Bai, L.; Hang, R. Q., Piezoelectric dressings for advanced wound healing. J Mater Chem B 2024, 12 (8), 1973-1990. Apply Now