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Special feature on UK synthetic biology resources: Liverpool GeneMill

Posted on 12/09/2016

The first of a series of special features on the SynBio SIG

In the first of a series of special features on synthetic biology, Linda D’Amore writes about the Liverpool GeneMill.

This article is the first of a series of special features on the SynBio SIG, which will highlight some of the fantastic resources that are available to the UK synthetic biology (SynBio) community.

In this edition, Linda D’Amore describes the activities and services available through the Liverpool GeneMill, which is one of nine strategic investments in DNA synthesis made through the Synthetic Biology for Growth Programme.

From Linda D’Amore, GeneMill Manager, Institute of Integrative Biology, University of Liverpool:

GeneMill provides end-to-end design, construction and phenotypic characterisation of small to large gene constructs or genetic circuits/pathways for academic and industrial applications. It officially launched on 4th February 2016, as an open access academic facility located within the Centre for Genomic Research (CGR) at The University of Liverpool. The CGR is one of the UK’s largest open access Next Generation Sequencing (NGS) facilities, containing all of the latest technologies for sequencing and transcriptomic analyses, including facilities to isolate and analyse single cells. Thus, GeneMill is equipping the scientific community with easy access to the skills and technologies required to explore the possibilities of SynBio. This service offers an opportunity for academic and industrial partners to access a wide range of expertise in Genomics, Bioinformatics and Metabolomics. We carry out contract research as well as offering opportunities for residential projects and training.

We are building a repository of functional DNA parts (Promoter, RBS, Tag, etc.) to fabricate libraries of constructs suitable for multiple hosts. In addition, we are using advanced liquid handling instrumentation to reduce reactions to sub-microliter volumes thereby increasing throughput and further reducing costs. We are working with various research communities to increase the size of this repository and are keen to engage with different communities to maximise the potential. Users will access these parts and may design their own for assembly into constructs through an online portal, which will be accessible soon. Support is available to guide the design process. The design process is fully supported from inception to completion.

Sequence-perfect clones can then be phenotyped in the desired host(s) using, for example, the RoboLector HT micro-fermentation instrument. This automates growth, monitoring, sampling and induction/inhibition of cultures and the exogenous genetic construct/circuit of interest. Such technologies are used to screen clones or to optimise culture/media conditions. Resulting parameters are transferable to large-scale fermenters and provide an excellent method for industrial scale-up at lower cost and development time.

Additionally, the metabolic phenotype can be directly analysed using a new set of state-of-the-art Mass Spectrometry instrumentation to provide Metabolomic and targeted metabolite identification and quantification. The Metabolomic data can be assigned to organism-specific pathways to give mechanistic insight. This can be used alongside other types of data such as gene expression or proteomic data to undertake integrated multi-omic analyses to understand levels of control and regulation. Finally, to provide the ultimate information to optimise new processes, Flux analysis of heavy-labelled substrate can be performed to gain insights into enzyme/pathway performance for optimising conversion processes. Therefore GeneMill offers a one-stop-shop service for the entire Design-Build-Test-Learn cycle.

While the whole SynBio pipeline is available as described, of course we also cater for projects requiring only parts of the whole, including:

  • DNA Design and Fabrication (e.g. DNA Synthesis, Community Parts Repositories| Plasmid Libraries | Pathway Fabrication)
  • Genome Editing Tools (e.g. CRISPR libraries, Cas9 constructs)
  • Metabolomic Analyses (e.g. Targeted/Untargeted Metabolomics | Compound ID | Data Modelling and Pathway-level Analysis | Flux Analysis)
  • Process Optimisation for Microbioreactor
  • Protein Design, Expression and Testing
  • Enzyme Prototyping
  • Culture/Expression Optimisation
  • Host-Construct Optimisation
  • Open Access to Equipment

If you are interesting in finding out more about the Liverpool GeneMill please contact Linda at: genemill@liverpool.ac.uk.

If you are involved in a UK SynBio resource and would be interested in promoting your activities through the SynBio SIG, please contact synbiosig@ktn-uk.org.