INTERNATIONAL COLLABORATION IN CHEMISTRY: THE DEVELOPMENT OF CHEMICAL PROBES FOR HOPANOID FUNCTION

We are interested in studying a set of chemicals found in bacteria called hopanoids. These chemicals were thought to be 'molecular fossils' that provided information on the evolution of how bacteria processed chemicals and obtained energy. However, recent work has shown that the function of hopanoids is more complex than originally thought. Indeed, it seems likely that hopanoids still play an important role in recent bacteria. In order to understand better the function of hopanoids we are planning to make new and unnatural hopanoid derivatives that have additional functions that will assist these studies. We plan to make fluorescent ('glow in the dark') hopanoids that will allow us to study where they are found in cells. We also plan to make molecular 'fishing rods', using hopanoids as the 'bait', to determine what other molecules, especially proteins, that hopanoids interact with in cells. These chemical 'probes' will allow us to understand how the hopanoids exert their effects within cells and may potentially identify new targets for harming bacteria, which will be interesting for the development of antibiotics.

The aim of this research is to create a suite of synthetic chemical probes to employ in the study of the hopanoids, in particular we expect to discover a range of hopanoid-binding proteins that play important roles in bacteria. These probes will likely be useful for other researchers in the area and hence we will, as far as possible, make them available to the community to facilitate their studies. If the demand is sufficient, we will investigate producing the probes commercially, most likely in partnerships with an existing chemical company or possibly through the formation of a spin out company. The commercialization of the probes would benefit the economic performance and competitiveness of the UK through the generation of profit and availability of scientific tools. Ultimately, in the long term (10-20 years), if the hopanoid-binding proteins are proven to be antibiotic targets then our work will be of significant benefit to the pharmaceutical industry, as it will underpin the discovery of novel antibiotic drugs. These drugs will contribute enormously to the UK economy in terms of providing profit, employment and investment of international pharmaceutical companies in the UK. In addition, as antibiotic resistance is a significant problem, antibiotic with novel modes of action will have a huge impact on quality of public health.

Another significant impact will be the world-class training provided to the two post-doctoral researchers. Due to the interdisciplinary nature of the project and the opportunities for exchange between two world-leading universities, the researchers will receive an outstanding scientific training. At the end of their contracts the researchers will be highly skilled and well qualified to enter high-level industrial or academic jobs alike. The training of these highly skilled individuals is of great benefit to the UK economy. Additionally, the researchers will benefit culturally from the opportunity to live and work at Caltech and Oxford, which are both diverse and culturally rich environments.