Fixed-term

Details Aldehyde dehydrogenases (ALDHs) catalyse the oxidation and detoxification of reactive endogenous and exogenous aldehydes into carboxylic acids via NAD+ coupled reduction. ALDH1 has been widely studied and is considered a marker of cancer stem cells (CSCs) and has been shown to be predictive of poor clinical outcome. Increased expression of cytosolic ALDH has been implicated as a mechanism whereby tumour cells may escape the lethality of cytotoxic anticancer alkylating agents, such as cyclophosphamide and related congeners. An improved understanding of the role ALDHs play within the tumour microenvironment and stem cell niche is crucial for unravelling their potential for biomarker and drug discovery strategies. We are looking for an enthusiastic student who is interested in establishing opportunities for how ALDH regulation or function can be exploited for drug discovery. In particular, the high ALDH expression that is a feature of many cancer types and CSC populations might contribute to enhanced DNA repair and this project seek to investigate how such knowledge can be harnessed in drug design. The student will be trained in 2D and 3D cell culture with a particular focus on ALDH-expressing sub-populations with stem cell properties, target interrogation (e.g. PCR, western blot, immunohistochemistry) including ALDH-chemical probe binding and effects on DNA damage response. The latter aspects will include the use of LCMS to study potential metabolic events caused as a consequence of functional ALDH activity. For students with a particular interest in chemical biology, there is also an opportunity to be trained in drug design. Entry requirements  Applicants should have at least 2:1 honours degree in Biomedical Sciences, Chemical Biology, Pharmacy or related degree. 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 type of course and use the keywords ‘cancer therapeutics’. Please include the title of the project on the ‘Research Proposal’ section; applicants are not required to write their own 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 PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee may also apply 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

Details Diversity-oriented synthesis (DOS) is a modern chemical methodology, which aims to synthesise small molecules that cover new chemical space with the possibility of finding unexplored biological targets or pathways that may be important for disease progression. The development of novel chemical entities (NCEs) is very important to the field of chemical genetics where chemical probes are used to probe known or unknown biological targets. This project will use DOS to enable the preparation of libraries of NCEs comprising heterocyclic pharmacophores, which will be used to probe the functional activity of enzyme targets. DOS will also be used to discover novel tool compounds including fluorescent molecules to probe regulation and functional activity of (i) aldehyde dehydrogenase (ALDH) isoforms highly expressed in cancer stem cells, (ii) cytochrome P450 (CYP) isoforms expressed in solid tumours or (iii) aldo-keto reductase 1C3 (AKR1C3) in prostate cancer. Conventional approaches such as computational modelling and medicinal chemistry will be employed in parallel to the use of DOS in order to develop chemical probes for enzyme interrogation. We are looking for an enthusiastic student to develop effective chemical tool compounds that can be used for target interrogation in cell-free and cell-based assays. The student will be trained in the design of novel bioactive molecules including synthetic and computational studies as well as target interrogation in functional activity assays. Biological studies will include investigations comparing naked lead compounds with co-crystal versions to acquire knowledge essential for turning good chemical probes into potential drug candidates. Entry requirements Applicants should have at least 2:1 honours degree in Chemistry, Chemical Biology, Pharmacy or related degree. 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 type of course and ‘cancer therapeutics’ as the keyword. Please mention the project title in the Research Proposal section; applicants are not required to submit 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 PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee may also apply 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

Details A major challenge in cancer therapy is to develop therapeutic agents that selectively target tumour cells but are not harmful to normal tissue. A promising way to increase selectivity of cytotoxic molecules (payloads) is to tether these to antibodies that preferentially bind to antigens expressed on the surface of membranes of cancer cells. This new type of therapeutics termed antibody-drug conjugates (ADCs) are being pursued for various oncology indications. Although 12 ADCs have been approved for clinical use, there is still much to learn about their stability, drug metabolism and pharmacokinetic (DMPK) properties. Depending on the type of ADC used, various aspects of the ADCs are implicated and contributing to dose limiting toxicities. The primary ADC toxicity is likely linked to premature release of the payloads and/or the lack of understanding of how ADC uptake for delivery of cytotoxic payload occurs in non-targeted normal tissue. To overcome some of these drawbacks, this project is focused on the modulation of payload toxicity via synthetic pharmacophore manipulation and evaluation of the DMPK properties of ADCs. We are looking for an enthusiastic student interested in exploring how to develop ADCs with improved clinical efficacy. You will be trained in payload and linker design, cell culture techniques with focus on cell uptake and target engagement and in DMPK techniques using a variety of different cell-free based assays and 2D and 3D cancer models. Entry requirements Applicants should have at least 2:1 honours degree in Bioengineering, Chemical Biology, Pharmacy or a related degree. How to apply Formal applications should be submitted via the University of Bradford web site. Applicants should register an account, and search for ‘cancer therapeutics’ as the course with ‘Postgraduate Research’ as the course type, then complete the form and include the project title on the Research Proposal section. Applicants are not required to write their own 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 PhD project; applicants will be expected to pay their own fees or have a suitable source of third-party funding. A bench fee may also apply 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

Details Colorectal cancer (CRC) is the 3rd most common cancer worldwide. Surgery is first line treatment and often in adjunct with chemotherapy. However, up to 20% of patients develop recurrent disease after treatment. Photodynamic Therapy (PDT) is an emerging anti-cancer treatment method, which can substantially improve the outcomes of treatment in CRC. PDT involves the administration of a photosensitising agent to cancers, followed by the irradiation of light to the cancer growth. This results in the activation of the photosensitising agent, eliciting cell death through the generation of reactive oxygen species and oxidative stress. This project will involve the investigation of PDT in CRC using different in vitro models of CRC. Recently, it has been identified that 2D cell cultures are not adequate and efficient in providing reliable and clinically representative outcomes of treatment. This is due to the limited capacity and application of 2D cell cultures and their lack of representation of clinical cancers. 3D spheroidal cell cultures and more recently, patient-derived organoids have been identified as vastly more improved and better models of CRC to pre-clinically evaluate treatments. In this project, PDT will be evaluated in simple 2D monolayer and more advanced 3D spheroidal cell monocultures and co-cultures of CRC. In our laboratory, we culture patient-derived organoids, directly from CRC patients in Leeds and will be used in this PhD project to study PDT treatments. The candidate will liaise with the colorectal surgery team at St James Hospital to collect and process CRC tissue specimens from theatre into organoids. Organoids will be subjected to PDT and other cancer treatments and interrogated on a molecular level to identify novel markers of chemoresistance. Methods: Cell line and tissue culturing, patient-derived organoid culturing, cell viability assays, fluorescent microscopy, immunofluorescence, immunohistochemistry, western blotting, RT-PCR, single cell analyses, statistical analyses How to apply Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account and select ‘Full-time PhD in Biomedical Science’ as the course, and then specify the project title when prompted. 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 Kim, W.S., Khot, M.I., Woo, H.M., Hong, S., Baek, D.H., Maisey, T., Daniels, B., Coletta, P.L., Yoon, B.J., Jayne, D.G. and Park, S.I., 2022. AI-enabled, implantable, multichannel wireless telemetry for photodynamic therapy. Nature communications, 13(1), pp.1-11. Khot, M.I., Perry, S.L., Maisey, T., Armstrong, G., Andrew, H., Hughes, T.A., Kapur, N. and Jayne, D.G., 2018. Inhibiting ABCG2 could potentially enhance the efficacy of hypericin-mediated photodynamic therapy in spheroidal cell models of colorectal cancer. Photodiagnosis and photodynamic therapy, 23, pp.221-229. Kondo, J., Endo, H., Okuyama, H., Ishikawa, O., Iishi, H., Tsujii, M., Ohue, M. and Inoue, M., 2011. Retaining cell–cell contact enables preparation and culture of spheroids composed of pure primary cancer cells from colorectal cancer. Proceedings of the National Academy of Sciences, 108(15), pp.6235-6240. Apply Now

Details Despite the number of mucoadhesive dosage forms available, the delivery of drugs through the mucosa still presents major challenges such as a lack of drug localization due to their short residence times, difficulties in accurate drug dosing and poor patient compliance. In addressing the unmet need, this project intends to develop novel hydrogel composite structure via continuous manufacturing technologies (twin screw extrusion, TSE) that overcome current challenges and deliver maximum patient benefits in treating a wide range of mucosal illnesses. The research objectives are to: Develop and optimise novel hydrogel composite formulation by continuous TSE process Mechanical and in vitro performance testing of composites In vitro and in vivo biocompatibility assessment. This project will give the student the opportunity to train and work across several disciplines including functional materials, mucoadhesive formulations, continuous pharmaceutical processing, materials characterisation, and toxicology and efficacy testing. The student will be working with a highly dynamic research team led by Dr Rahamatullah Shaikh (Centre for Pharmaceutical Engineering Sciences), Dr Colin Seaton (Chemistry) and Dr Steven Shnyder (Institute of Cancer Therapeutics). The main research activities of the Principal Supervisor Dr Shaikh’s research group are to design and develop novel formulation strategies and next-generation drug delivery technologies to enhance therapeutic efficacy and patient compliance. There will also be an opportunity to collaborate with industry professionals and prominent academic leaders in shaping this significant PhD project. The skills that the student will acquire during this PhD program are highly transferable and suitable for a potential career in academia, R&D or industry in the UK or internationally. Eligibility The successful candidate will have a background in Pharmacy, Pharmaceutical Sciences, Chemistry, Chemical Engineering, Biomedical Engineering, Health and allied areas and/or related disciplines. 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 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 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

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

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

Details The main research activities of my research group is to design, develop, novel formulation strategies and next-generation drug delivery technologies to enhance therapeutic efficacy and patient compliance. Despite extensive research in the field of cocrystals, there is still a large knowledge gap on development of cocrystal end-product formulations especially considering continuous wet granulation process. In order to design robust formulation process for cocrystals dosage forms, it is essential to have thorough mechanistic understanding and engineering of paradigm process. The primary objective of the current project is to gain a mechanistic understanding of the selection of additives and their effect on hydrate formation and cocrystallization. In this study, a Quality-by-Design (QbD) approach incorporated with process analytical technology (PAT) monitoring will be used to gain an understanding of the cocrystal twin screw wet granulation (TSWG) process and optimize granule and tablet formation. The students will be working with a highly dynamic research team led by Dr Rahamatullah Shaikh, Professor Adrian Kelly and Prof Anant Paradkar. There will also be an opportunity to collaborate with industry professionals and prominent academic leaders in shaping this significant PhD project. During the PhD programme student will be offered training in different disciplines chemistry, drug formulation, chemical engineering (Centre for Pharmaceutical Engineering Sciences and Polymer Interdisciplinary Research Centre) , and such as cocrystallization, wet granulation, continuous pharmaceutical processing, process analytical technologies, chemometrics, materials characterisation, as well as other project specific training. The skills that the student will acquire during this PhD program are highly transferable and suitable for a potential career in academia, R&D or industry in the UK or internationally. Eligibility The successful candidate will have a background in Pharmaceutics, Chemistry, Chemical Engineering and/or related disciplines. 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 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 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