Ellis:Research

Latest Update: Feb 2012

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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

Synthetic Yeast Chromosome XI
Project Type: Foundational and Applied
Project Members: Ben Blount, Dejana Jovicevic
Collaborators: Jef Boeke, Sc2.0 International 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 TAL-effector technology
Project Type: Foundational and Applied
Project Members: Ben Blount, 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: Rhys Algar, Wei Pan
Collaborators: Guy-Bart Stan, Microsoft
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, Jaksa Novicic
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.

Standards and parts for synthetic biology
Project Type: Foundational
Project Members: Georgios Pothoulakis, Nina Zhu
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. Working in a collaboration with BIOFAB USA and Imperial's own BIOFAB group, we are developing new standards for part characterisation and genome design in E.coli, and new part libraries for engineering synthetic yeast.

Engineering thermophilic synthetic biology
Project Type: Foundational and Applied
Project Members: Elena Martinez-Klimova, Ben Reeve
Collaborators: David Leak, TMO Renewables
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.

Parasite Protease Detection
Project Type: Applied
Project Members: Nicolas Kylilis
Collaborators: Paul Freemont, Geoff Baldwin, Bill and Melinda Gates Foundation
Almost all parasites release specific proteases during their life-cycle in order to invade and ingest surrounding tissues. Rapid, cheap detection of such proteases offers a novel method for diagnosis and tracking of parasistic disease, such as Schistosoma. Following on from Imperial's 2010 iGEM team and with generous funding from the Bill and Melinda Gates Foundation, we are developing a modular whole-cell biosensor solution to detect specific proteases released by parasites.

Cyborg Biosensors
Project Type: Applied
Project Members: Piotr Faba, Charles Fracchia
Collaborators: Tony Cass, IBM
A single E.coli cell can sense subtle changes in its environment such as the presence of pollutants or rare metals, however it takes millions of E.coli, all producing fluorophores or dyes to relay this message back to a human eye. To tackle this scale-barrier between the microbe world and human world we're developing a simple genetic part that gives an output that can be recorded by cheap nanotechnology detectors. A cyborg scheme interfacing disposable electronics with re-programmable microbes will offer low-cost, high-sensitivity environmental sensing solutions.