Project 12 - Exploring the anti-cancer activity and molecular targets of avenacins
Applying for Summer 2025
Supervisor: Dr Sean Tattan
Secondary supervisors: Dr Emily Hobson, Dr Amr Eldemerdash, Dr Rebecca Casson, Professor Anne Osbourn and Professor Maria O’Connell.
School/Institutes: School of Biological Sciences, UEA, School of Chemistry, Pharmacy and Pharmacology, UEA, John Innes Centre
Introduction: Cancer remains a significant public health challenge and is among the leading causes of mortality in the UK, accounting for approximately 167,000 deaths annually. Addressing this burden necessitates the identification and application of novel anti-cancer therapeutics. One such promising candidate are avenacins. Avenacins are triterpene glycosides derived from oat root and landmark studies by the Osbourn group have recently facilitated the synthesis of these compounds. The O’Connell laboratory has previously demonstrated that these natural products and derivatives also have potent anti-proliferative effects at nanomolar concentrations in human cancer cells, however the molecular mechanism via which they exert this effect is poorly defined.
Aims and objectives: This project will leverage the auto-fluorescent properties of avenacins using advanced bioimaging techniques including widefield, confocal, and super-resolution fluorescence microscopy, to visualise avenacins loaded into cells from a variety of cancer types. The resulting large-scale imaging data will be processed and analysed by high-content image analysis pipelines developed in Python, which will allow for fluorescent signal segmentation, co-localisation, and particle tracking. By mapping the subcellular and organellar localisation of avenacins, the study aims to uncover valuable insights into their potential molecular targets. Subsequently the project will aim to characterise the effect of avenacins on the propagation of candidate intracellular signalling pathways to elucidate the mechanism via which they may confer anti-cancer effects.
Skills Gained: To achieve this body of work, the student will gain experience in human cell culture (2D and 3D), immunocytochemistry, bioactivity and viability assays (e.g. MTS and LIVE/DEAD), flow cytometry, real time PCR, fluorescence microscopy, R and Python programming.
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References: (1) Reed J, et al (2017). A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules. Metab Eng. 42,185-193. (2) Kemen AC et al (2014). Investigation of triterpene synthesis and regulation in oats reveals a role for beta-amyrin in determining root epidermal cell patterning. Proc Natl Acad Sci USA, 111, 8679-8684.