Ellis:Research

Latest Update: June 2014

---

Research in the Ellis Lab focuses on advancing our understanding of nature through genome engineering and accelerating biotechnology through the use of synthetic biology. Projects are either foundational work, applied work or a nice mix of both.

Current Projects

Synthetic Yeast Chromosome XI
Project Type: Foundational and Applied
Project Members: Ben Blount, Rob McKiernan, Dejana Jovicevic
Collaborators: Jef Boeke (NYU), Yizhi Cai & Al Elfick (Edinburgh), 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 Johns Hopkins University, 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, aiming to design, synthesise and assemble the complete 666 kbp chromosome XI. During construction we will investigate genome design and topological effects such as nuclear structures and how these can be used to optimise gene expression in metabolic engineering.

Synthetic Biology with engineered modular regulation
Project Type: Foundational and Applied
Project Members: Ben Blount, Marios Koutsakos, Tim Weenink
TAL effectors are a relatively new form of DNA-binding protein that have a programmable DNA-recognition code. This means that they can be re-engineered repeatedly to bind to custom DNA sequences. We have now shown that modular TAL-effectors can be customised to be orthogonal repressors (TALORS) for yeast promoters - effectively acting as independent wires in logic systems. This offers a route to scalable logic systems in yeast synthetic biology. We are now looking to improve on this technology to generate a range of custom-built transcription factors which we can apply to advanced logic networks such as oscillators and memory systems.

Investigating device-chassis interactions
Project Type: Foundational
Project Members: Francesa Ceroni, Rhys Algar
Collaborators: Guy-Bart Stan
Most gene devices demonstrated in synthetic biology have been high-expression strength regulatory networks 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 mechanisms. In this project, we are trying to quantify the threshold for gene device cloning into the E.coli chassis by examining a standard synthetic networks expressed at a variety of different strengths in plasmid systems of varying copy number. The intention is to define a quantitative standard for inserting gene devices into chassis cells and build a predictive model to aid future design.

Combinatorial modular assembly of gene networks and pathways
Project Type: Foundational and Applied
Project Members: Arturo Casini, Ali Raza Awan
Collaborators: Geoff Baldwin, James MacDonald
The availability of gene synthesis is increasing rapidly, yet there is no straightforward lab-bench method to arrange modular gene units into larger assemblies with pre-defined positions. In this project we will demonstrate a new method to rapidly assemble gene units in a pre-defined order and showcase the technique to combinatorially assemble diverse synthesis pathways and gene regulatory networks using standardized parts. As well as demonstrating a rapid new assembly technique, the project will yield synthetic cells with high production of high-value therapeutic molecules.

Engineering thermophilic synthetic biology
Project Type: Foundational and Applied
Project Members: Elena Martinez-Klimova, Ben Reeve
Collaborators: David Leak
Engineering new function into well-characterised cells is one of the major goals of synthetic biology, but one phenotype almost impossible to add to cells like E.coli is thermostability. Instead, our lab is kick-starting synthetic biology in a Geobacillus species thermophile by developing standard measurement protocols with aerobic and anaerobic fluorescent proteins and charactersing libraries of standard, synthetic parts. We will use these to improve and diversify existing biofuel production pathways to generate high-yields and new products.

Intrinsic Biocontainment
Project Type: Foundational and Applied
Project Members: Ollie Wright and Mihails Delmans
Collaborators: Guy-Bart Stan, DSTL
Many projected applications of synthetic biology require engineered microbes interacting with the environment. Plasmid-based contructs are attractive for synthetic biology as they are easy to engineer and unless they confer an advantage, they can be quickly lost outside of lab conditions. However, they are also susceptible for take-up by microbes in the ecosystem via horizontal gene transfer. Following on from Imperial's 2011 iGEM team and with funding from the DSTL, we are now developing a set of plasmids and specific E.coli hosts that are less likely to transfer by horizontal gene transfer and so better suited for future applications such as contaminant biosensing.

Pattern Formation
Project Type: Foundational
Project Members: Georgios Pothoulakis, Alejandro Granados, Michael Florea and Isuru Goonatilake
Collaborators: The Leverhulme Trust, Reiko Tanaka
Differentiation of genetically-equivalent cells allows single-cell cultures to diversify into patterns or achieve division of labour for tasks. In E.coli we are rewiring the regulatory network of two-component systems to achieve bimodal responses in gene expression that can be used to drive differentiation. In lab yeast, we are adding genes from ancestral strains that grow in a filamentous form when stressed and placing these under control of tunable, inducible promoters so that we can switch yeast colony growth from standard to branched fractal patterns.