Project: Molecular mechanisms of action of dietary antioxidants and chromatin modifying compounds
The medicinal properties of the leaves and fruit of Olea europaea (olive tree) have been known since antiquity, and consumption of olive oil has been associated with a decreased risk of cardiovascular disease and certain cancers. Increasingly, there is interest in the biological properties of the molecular constituents of olives. For example, hydroxytyrosol has been shown to be a potent antioxidant and has anti-atherogenic and anti-cancer properties. However, the specific constituents responsible for various beneficial effects of olives, as well as their molecular targets, are not well known. The main aim of this project is to use molecular computational modeling and simulation methods to identify key molecular targets of specific bioactive components of olives, and to produce molecular-level characterisation of their mechanisms of action. The outcomes of this project will aid development of novel therapies derived from dietary compounds, which may have substantial advantages over synthetic drugs, including lower dosage requirements and reduced risk of adverse side effects. This project will focus on identifying the mechanisms of action of dietary olive compounds in inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used therapeutic agents around the world, commonly used to reduce pain. However, there are adverse effects with the use of NSAIDs, including gastrointestinal bleeding and cardiovascular effects. Hence, there has been a rise in the development of alternatives to traditional NSAIDs. A previous study found that oleocanthal, a phenolic compound derived from olive, had similar effects to ibuprofen, a commonly used NSAID. But there is a multitude of additional compounds in olive that have yet to be investigated. Hence, this project will study the mechanisms of olive derived compounds in inflammation using molecular computational modeling and simulation approaches. Enzymes involved in inflammation pathways will be explored as potential targets for olive-derived compounds, including cyclooxygenase (COX). Elucidation of the mechanism of action in the inhibition of COX and other related enzymes will be valuable in developing novel drugs for the treatment of inflammatory diseases.
This project will largely be undertaken at the Alfred Centre, AMREP.
The Karagiannis group aims to understand the role of dietary antioxidants and chromatin modifying compounds on the genome and epigenome in health and disease. They develop predictive models of wound severity and potential for repair in the context of diabetic foot ulcers. This research direction also involves the development of new potential therapeutics.