Impact case study database

Increasing the pace of drug discovery is a key global goal, both to increase treatment options ( e.g., for cancer) and to provide alternative therapeutics in situations where resistance is an issue ( e.g., bacterial antibiotic resistance). This requires there to be appropriate libraries of potentially active compounds from which lead compounds can be identified. Animal venom components derived from both vertebrates ( e.g., snakes) and from invertebrates ( e.g., spiders and scorpions) represent an under-exploited source for such libraries of potential therapeutics, as the venom of any given species may contain hundreds of different active components. Given the complexity of venoms, their exploitation in the development of therapeutics requires characterisation and fractionation in order to identify active components. In order to achieve this, the animals concerned must also be safely and humanely handled and housed. It is also critical that those working in drug discovery recognise that venoms are important sources of lead compounds. Working with a local biotechnology company, Venomtech Ltd., CCCU research has addressed each of these challenges. This collaboration therefore exemplifies both the Unit of Assessment’s (UoA’s) approach of undertaking research that addresses the specific needs of stakeholders via coordinated and sustained activity, and the University’s approach of seeking to deliver deep local and regional impact that has focussed wider influence.

Research led by Dr Carol Trim has focussed on the potential of venom components for the development of cancer therapeutics, with a specific aim of identifying factors that block the Epidermal Growth Factor Receptor (EGFR). This receptor is present on the surface of many cell types but is overexpressed in a large number of cancers, and is important in cancer cell growth. Dr Trim’s work has shown, in cell culture assays, that venom and venom components from multiple species of snakes, scorpions and spiders lowers the growth and viability of many cancer cell lines, and has identified both line-specific and venom-specific effects. Subsequent analysis of the effects of these venoms on EGFR and related receptor tyrosine kinase family members – highly conserved and functionally important druggable targets for cancer therapy – has identified widespread changes in protein phosphorylation [R1]. Further characterisation of these anti-cancer effects has shown that some are mediated via interactions with EGFR, whilst others have different mechanisms of action [R1]. This work has therefore identified multiple candidate venoms and venom fractions that represent candidates for therapeutics targeting EGFR, and for characterising novel pathways that can block cancer cell growth. The work also clearly shows that there are many potentially valuable biologically active components present in these venoms. Foundational work that allowed this research to be performed has also identified ways to optimise the processing and storage of venoms, and has identified ways to extract venom from novel sources [R2]. These elements of the work have therefore increased the venom yield per animal, allowed venom extraction from novel species, and extended the product shelf life of extracted venom and venom components.

A similar strategy has been used to identify venoms and venom components that have antimicrobial and antifungal effects. Here, assays treating multiple microbial species with venom and venom components from different species have shown effects on survival and growth. This indicates that venoms also represent a rich source of lead compounds for the identification of anti-microbial drugs. Research conducted in collaboration with Dr Sterghios Moschos at Northumbria University has also characterised the oral and venom microbiome of snakes, spiders and scorpions [R3]. That viable microorganisms are found in venoms challenges the dogma of venom sterility, and explains why venoms have evolved antimicrobial peptides. This aspect of the CCCU research therefore provides the essential theoretical framework that justifies venoms as a source of antimicrobial drug candidates.

In combination, this body of research has therefore identified and validated venoms as sources of lead compounds for work seeking to develop antimicrobials, antifungals and cancer treatments. Elements of this work are ongoing and aim to characterise specific venom components and to understand their mode of action, i.e., to generate further impact by defining specific candidate therapeutics. The completed work to date has however already had significant impact on Venomtech Ltd., by supporting revenue increases and company expansion.