Fixed-term

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