An exciting opportunity has arisen for a Postdoctoral Researcher to join the Wilkinson Group at the John Innes Centre, working in collaboration with the Hutchings lab, on a project titled: Global activation of silent and cryptic biosynthetic pathways in Streptomyces species.

About the Wilkinson Group

We are an inter-disciplinary team that includes chemists, biochemists and micro/molecular biologists who work on the discovery, biosynthesis, and biosynthetic engineering of microbial specialised metabolites, and on understanding the role these metabolites play in the environment. We focus on anti-infective molecules and additionally study their molecular targets & mechanisms of action, and the immunity mechanisms employed by their producer organisms.

Project background

Streptomyces specialised metabolites form the basis of two thirds of clinically used antibiotics but only 3% of the specialised metabolite pathways encoded in their genomes have been matched to molecules. The majority are “silent” which means they can be identified in genome sequences, but they are not expressed under standard laboratory growth conditions. Streptomyces bacteria have also been found to contain “cryptic” biosynthetic gene clusters (BGCs) which cannot be predicted by similarity search-based tools such as antiSMASH and likely encode new molecules. Regulation of silent and cryptic gene clusters is complex and multilevel, and this makes it extremely challenging to understand.

The project

We are taking a high-level approach to activate multiple silent and cryptic gene clusters in Streptomyces bacteria through the manipulation of global regulators that are highly conserved. The project will focus on a family of highly conserved transcription factors which appear to be at or near the top of a hierarchy of regulators that coordinate the lifecycle of Streptomyces with specialised metabolism: our preliminary data show that manipulation of these TFs actives the expression of multiple silent and cryptic BGCs in Streptomyces venezuelae, leading to the production of new molecules.

The role

The successful candidate will isolate and structurally characterise new specialised metabolites produced by a panel of engineered Streptomyces strains and link them to BGCs. Building on these data you will delineate the biosynthesis of the new molecules and investigate their bioactivity in a range of biochemical and cellular assays.

The ideal candidate

You will have a PhD in Natural Products Chemistry with in-depth knowledge of natural product isolation and structure elucidation, especially when working with small quantities of material, and of metabolomics and molecular networking.

You will have a proven ability to perform research and develop novel ideas in natural products chemistry and discovery. Experience in delineating natural product biosynthetic pathways and a proven record in scientific writing are highly desirable.

Additional information

 A starting salary of £40,100 is guaranteed for candidates who can evidence their PhD certificate at appointment. Candidates awaiting confirmation of their PhD award will be appointed at £39,000 until evidence is provided.

For further information and details of how to apply can be found here or contact the Human Resources team on 01603 450814 or nbi.recruitment@nbi.ac.uk quoting reference 1006209.

This role meets the criteria for a visa application, and we encourage all qualified candidates to apply. Where the successful applicant requires a visa, we will fund the costs for their visa and the Immigration Health Surcharge. Please contact the Human Resources Team if you have any questions regarding your application or visa options.

We are an equal opportunities employer, actively supporting inclusivity and diversity.  As a Disability Confident organisation, we guarantee to offer an interview to all disabled applicants who meet the essential criteria for this vacancy. We are proud to hold a prestigious Gold Athena SWAN award in recognition of our inclusive culture, commitment and good practices towards advancing of gender equality. We offer an exciting, stimulating, diverse research environment and actively promote a family friendly workplace. The Institute is also a member of Stonewall’s Diversity Champions programme.

The John Innes Centre is a registered charity (No. 223852) grant-aided by the Biotechnology and Biological Sciences Research Council.

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