Collaborative research visit to the California Institute of Technology

Hopanoids are a poorly understood class of steroid-like molecules produced by bacteria. It has long been assumed that hopanes, molecular fossils of hopanoids, reveal a history of the rise of important microbial metabolisms such as oxygen-forming photosynthesis, but recent results from Prof. Dianne Newman's laboratory (California Institute of Technology) have challenged this interpretation. It is now apparent that our ability to interpret what hopanes reflect about geochemical and/or biological evolution is hindered by a poor understanding of their function within cells. Prof. Newman's studies of hopanoid formation and localisation in the hopanoid-producing bacterium Rhodopseudomonas palustris TIE-1, suggest that hopanoids play a crucial role in growth and cell division under certain conditions. To understand their biological roles at the molecular level, we require a chemical toolkit to study hopanoid localisation and to identify the proteins that bind them. Dr Conway and Prof. Newman aim to jointly develop this toolkit of molecules. The proposed research visit will allow Dr Conway to acquire the skills required to produce the starting point for this toolkit, improve some of the processes involved in purification and try some of the chemical reactions required to make the required molecular tools.

This proposal seeks support for a research visit to the California Institute of Technology which will enable further collaborative research between the groups of Prof. Dianne Newman (California Institute of Technology), Prof. Robert Grubbs (California Institute of Technology) and Dr Stuart Conway (Oxford), the aim of which is to create a toolkit of synthetic chemical probes to underpin the study of the hopanoids. Ultimately, we aim to discover a range of hopanoid-binding proteins that play important roles in bacterial function. These chemical probes will be useful for other researchers in the area and hence we will make them available to the community to enable 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 commercialisation 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 significantly 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 large impact on quality of public health.