Collaborative research visit to the California Institute of Technology

Lead Research Organisation: University of Oxford
Department Name: Oxford Chemistry


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.

Planned Impact

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.


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Description This grant is a travel award linked with EP/K000888/1, which focuses on the development of molecular tools to study hopanoids.

The grant enabled Prof. Conway to undertake a 6 month sabbatical visit to Caltech as a Visiting Associate. During this time he acquired new molecular biology skills by spending time working in the laboratory of Prof. Dianne Newman. These skills have had a profound impact on the research being conducted in Prof. Conway's group, as problems can now be approached using complimentary chemical and biochemical techniques.

The collaboration with Prof. Newman was strengthened and expanded during this visit. Prof. Conway and Prof. Newman are now exploring routes to obtain further collaborative funding. They have a mutual interested in bacterial function, which can potentially be exploited to develop new antibiotic therapies.
Exploitation Route N/A
Sectors Agriculture, Food and Drink,Chemicals,Pharmaceuticals and Medical Biotechnology

Description Dianne Newman - California Institute for technology 
Organisation California Institute of Technology
Department Division of Biology and Biological Engineering (BBE)
Country United States 
Sector Academic/University 
PI Contribution We have been synthesising molecule tools, based on hopanoids, to probe bacterial systems that the Caltech team are interested in.
Collaborator Contribution The Caltech team have been using our tools to pull-down hopanoid-binding proteins, and conducting proteomics experiments to identify the binding partners.
Impact Wu, C. H. et al. Quantitative hopanoid analysis enables robust pattern detection and comparison between laboratories. Geobiology 13, 391-407 (2015). DOI:10.1111/gbi.12132. We are exploring the possibilities for securing further collaborative funding. Prof. Conway visited Caltech and learnt new molecular biology skills.
Start Year 2013