Regulation, biosynthesis and mode of action of formicamycins, promising new antibiotics with a high barrier to resistanc

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

The proposed work will generate a range of impacts. We describe who will benefit and how below:

1. INDUSTRY. The techniques we use will be of interest to industry, particularly antibiotic development companies such as Warp Drive BIO and Demuris who use genome mining for antibiotic discovery, and Isomerase Therapeutics who develop new molecules through biosynthetic engineering. We are at the forefront of efforts to use CRISPR/Cas9 genome editing for antibiotic discovery and development in Streptomyces bacteria, in particular with the work we have and will do with S. formicae. To our knowledge no one has used CRISPR/Cas9 editing to the same extent and with the same success in any other Streptomyces strain. Thus, our work will provide a proof of concept for this approach and will also yield new molecules and strains that will be of value to industry. We will disseminate our results through publications and at conferences, including industry focussed meetings, e.g. via the Industrial Biotechnology Alliance (IBA) on the Norwich Research (Hutchings and Wilkinson lead the IBA Anti-infectives theme), the Biotech and Life Science Sector group set up by the New Anglia Local Enterprise Partnership (Hutchings is a member) and through our own industry and knowledge exchange contacts. Hutchings has been Associate Dean for Innovation in Science at UEA since 2013 and Wilkinson is co-Director of the BBSRC Natural Products discovery and Bioengineering Network (NPRONET), and a co-founder of Isomerase Therapeutics, so they are well connected. We will share more widely through social media and press releases.

2. SOCIETY. Impact will be achieved long term by the development of new antibiotics either directly via our work on the fasamycins and formicamycins and indirectly when the techniques we are developing are adopted by others to stimulate early stage discovery. Identifying the molecular target for the formicamycins will allow others to develop alternative chemical classes with activity against this target. Impact will also be achieved through public and policy engagement with our research and education about antibiotics and AMR. Two of our co-supervised PhD students did 3-month internships at Westminster in 2017: Rebecca Devine worked with CMO Dame Sally Davies and Sarah Worsley worked in the Science Policy office. These are useful links and Dame Sally Davies has been highly supportive of our research and public engagement efforts, including a book we published on antibiotics with the Science, Art and Writing Trust (http://www.sawtrust.org/buy-the-books/saw-antibiotics/). We will use these contacts to highlight our work and the work of our colleagues in the UK around AMR. Hutchings and Wilkinson have strong track records in public engagement in schools, through public lectures and at major public science events including exhibits at the Royal Society Summer Science Exhibition 2014, the BBSRC Great British Bioscience Festival 2014, Big Bang Science Fair 2015, Norwich Science Festival 2016 and Latitude Festival 2017. Hutchings won a UEA award in 2015 for his outstanding contribution to public and community engagement and the applicants will both continue to engage widely with the public through all available avenues to talk about their work on antibiotics.

3. UEA and JIC. There are potential economic benefits to UEA and JIC through licensing of materials (strains, constructs, molecules) developed during this project. Intellectual property will be protected and licensed by the Research and Innovation Office at UEA and / or Plant Biotech Ltd at the JIC. Another benefit to our host institutes and the Norwich Research Park will be the publicity gained by our work through communication of results at public engagement events and through the media and social media.