Ellis:Research

Latest Update: April 2010

Research in the Ellis Lab focuses on advancing biotechnology through the use of synthetic biology. Projects fall into one of two categories or belong in both:

• 1. Foundational Synthetic Biology

Developing the tools for rapid, predictable engineering of biological devices and systems.

Examples: biopart design, assembly techniques and device synthesis, part and device characterisation, standardisation, chassis systems, mathematical models, design simulations

• 2. Applied Synthetic Biology

Using the synthetic biology approach in biotechnology applications .

Examples: combinatorial synthesis of pathways, modular design of biosensors, cheap inducer systems for biosynthesis

Current Projects

New standards for BIOFAB projects
Project Type: Foundational
Project Members: Ben Blount, Serge Vasylechko, Riham Satti
Collaborators: Richard Kitney, BIOFAB USA
Synthetic biology requires professional characterisation of standardised parts to enable predictable and scalable construction of complex and robust devices and systems. To characterise biological parts it is useful to have a reference standard part to which it can be compared. This has been demonstrated by Kelly et al. for housekeeping promoters in E.coli. Working in a collaboration with BIOFAB USA and Imperial's own BIOFAB group, we are developing two new standards for part characterisation: (1) a standard reference promoter for yeast selected from systems biology screening, and (2) an ultra-efficient GFP coding region with various degradation tags for dynamical characterisation at low copy numbers.

Investigating device-chassis interactions
Project Type: Foundational
Project Members: Rhys Algar, Hung Hsu
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 feed-forward loop motif 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 diverse Carotenoid production pathways in yeast
Project Type: Foundational and Applied
Project Members: Arturo Casini
Collaborators: Geoff Baldwin
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 in yeast. The modular gene units from the carotenoid pathways are driven by regulated promoters from a pre-existing library, and combinatorial assembly with these will produce pathways with a variety of metabolic fluxes. As well as demonstrating a rapid new assembly technique, the project will yield synthetic yeasts with high production of high-value carotenoid molecules.

Bottom-up design of orthogonal E.coli promoters
Project Type: Foundational
Project Members: Fabio Chizzolini
Synthetic biology has made great advances in its first decade but the complexity of devices has not exploded exponentially as expected. One of the major reasons for this is the lack of different parts, and specifically a dearth of regulated promoters is holding synthetic biology back. In E.coli our understanding of these promoters is advancing fast enough to consider building them up from scratch, but where do we start? In this project we will evolve a new orthogonal promoter system that uses a mutated Sigma Factor and mutated core promoter DNA sequence, so that these designer promoters are only recognised by the designer sigma factor under our control. This will lay the foundation for building a whole set of 'synthetic biology ONLY' promoters and devices that can sit in cells and yet only have limited interaction with the host cell systems.

Part characterisation for thermophilic bacteria
Project Type: Foundational
Project Members: Elena Martinez-Klimova
Collaborators: David Leak
Synthetic Biology has had considerable success importing function from throughout nature into the industrial workhorse organisms of E.coli and yeast. However, one function desirable in industrial biotechnology - growth at high temperatures - would be almost impossible to introduce, as it would require radical rewriting of every gene to code for heat-resistance. The sensible alternative is to begin to describe synthetic biology for a thermophilic chassis. In this project we have identified an organism which we believe is the "E.coli of thermophiles" and intend to characterise bioparts for this chassis using flow cytometry with an engineered thermophilic GFP.