RESEARCH

Current Projects

Synthetic Yeast Chromosome XI

Project Members: Ben Blount, Glen Gowers
Collaborators: Jef Boeke (NYU), Yizhi Cai (Manchester), Steve Oliver (Cam), Paul Freemont, Sc2.0 Consortium
Sc2.0 is a high-profile, international project to do the first full synthesis of a eukaryotic cell genome, the model yeast species Saccharomyces cerevisiae. Led by Prof Jef Boeke at NYU, USA, an international consortium is now established to re-synthesis and make to design changes to all 16 yeast chromosomes. Our group is leading the UK effort in the consortium, with the design, synthesis and assembly of the complete 666 kbp chromosome XI. During construction we will investigate DNA assembly methods and genome design and topology and learn how these can be used to optimise gene expression in metabolic engineering experiments.
Funders: BBSRC, EPSRC

Investigating device-chassis interactions

Project Members: Olivier Borkowski, Brooke Rothschild-Mancinelli
Collaborators: Guy-Bart Stan, Francesa Ceroni, Richard Murray (Caltech)
Most synthetic gene constructs used in synthetic biology have been high-expression strength regulatory networks and pathways hosted on mid-to-high copy number plasmids in E. coli. Despite being relatively simple and small, these devices are thought to be close to the maximum tolerated by the host cell – if they were any larger they would impinge on the host cell’s own growth. In this project, we are quantifying the threshold for cloning into E. coli by testing a variety of synthetic networks and pathways expressed at different strengths in plasmid systems of varying copy number. We aim to define a quantitative standard for inserting synthetic constructs into cells and use a predictive model to aid future design of cells with predictable growth rates.
Funders: EPSRC

Combinatorial modular assembly of gene networks and pathways

Project Members: Will Shaw, Glen Gowers 
Collaborators: AstraZeneca, Sphere Fluidics, GSK
We are utilising new DNA assembly methods and strategies to rapidly build diverse, combinatorial DNA construct libraries yielding complex metabolic and signalling pathways. These methods are now being applied to make E. coli and yeast produce a variety of therapeutic molecules including antibiotics, antioxidants, antitumour agents and appetite suppression hormones. Working with GSK, we are using these methods to synthesise drug precursors. Working with AstraZeneca, we are now linking therapeutic production to external health cues, by refactoring cell signalling pathways. We are also working with Sphere Fluidics to develop a novel picodroplet microfluidic system that sorts the highest producing engineered cells by rapidly screening their MS profiles.
Funders: BBSRC, AstraZeneca, Sphere Fluidics, GSK

Engineering advanced materials from living bacteria

Project Members: Charlie Gilbert, Marcus Walker, Vivianne Goosens, Linda Dekker
Collaborators: Koonyang Lee, Tim Lu (MIT), Textiles Futures Research Centre (UAL), Customem Ltd.
The materials of the future will be manufactured by biology but programmed by synthetic biology to have diverse functions. We are working with bacteria that overproduce carbohydrate material polymers and functionalising this material as it is made in order to give it new properties. We are also working on programming the polymerisation of protein-based materials with enzymatic and sensing functions built in. Together these two approaches aim to build new interwoven, functionalised composite materials programmed by genetic engineering of microbial produces.
Funders: EPSRC, DSTL, SynBiCITE, MIT-ICL MISTI