Design, synthesis and evaluation of novel polysialyltransferase inhibitors as anti- metastatic agents

Polysialic acid plays an essential role in neuronal development, but by adulthood is absent from the human body. Its biosynthesis is regulated by two polysialyltransferases (polySTs). Polysialic acid is aberrantly re-expressed on the surface of many tumours, where it plays a key role in diseases progression and metastasis. It is therefore an attractive anti-cancer target (see Current Cancer Drug Targets, 2012, 12, 925-939).

The Institute of Cancer Therapeutics, at the University of Bradford, is focused on the development of novel polyST inhibitors, using computational chemistry to aid compound design. We have developed assays to assess compound inhibition (see Analyst, 2016, 141, 5849-5856) and have utilized tool compounds to show the potential of the approach (see PLoS ONE, 2013, 8, e73366). The wider project benefits from funding from programme funding from Yorkshire Cancer Research and more recently from the Wellcome Trust. The student will join a successful, motivated multidisciplinary team with expertise in medicinal chemistry, pharmacology and drug analysis.

The group has a series of hit polyST inhibitors with potential for further development. The project will focus on the synthesis of the next generation of inhibitors, utilising computational chemistry to aid compound design. Training in compound synthesis, purification (including preparative HPLC) and analysis (LC-MS, NMR) will be provided. Synthesised compounds will be evaluated in cell-free HPLC-based enzyme inhibition assay, with the most promising compounds then screened in cell-based assays, all in-house.

How to apply

Formal applications can be submitted via the University of Bradford web site. Applicants should register an account, select 'Full-time PhD in Cancer Therapeutics' as the course, and include the project title on the Research Proposal section.

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.

Faculty of Life Sciences

The faculty comprises a mixture of academic divisions, research centres and outreach facilities. We provide high-quality teaching with a professional focus and engage in cutting-edge research – which we seek to apply through our extensive links with industry and business. We also offer a wide range of postgraduate taught and research courses.

Many of our academics are active researchers and international research experts.

Our interdisciplinary research themes are focus on:

• Computational and Data-driven Science
• Interface of Chemistry Biology and Materials
• Health, Society, People and Place
• The Life Course

Our research centres include:

• Centre for Pharmaceutical Engineering Science
• Digital Health Enterprise Zone
• Institute of Cancer Therapeutics
• Wolfson Centre for Applied Research

University investment in research support services, equipment and infrastructure provides an excellent research environment and broad portfolio of developmental opportunities. 

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.