LEC Seminar: The application of ‘engineering statistics’ to metabolic engineering and gene network engineering
Biological engineering presents an attractive route to tackle many of the world’s challenges, for example, the production of fuels and chemicals from renewable sources. Here, I will describe the construction of metabolic pathways for the biosynthesis of petroleum-replica biofuels. Our metabolic engineering strategy involved the introduction of up to 10-genes from four organisms into Escherichia coli. The resulting range of hydrocarbons produced are not naturally biosynthesised. Moreover, they are structurally and chemically identical to the fuels they seek to replace. Because of this, they circumvent the need for wholesale changes to our transportation infrastructure that is demanded if we increase our use of traditional biofuels. Biology, however, is a complex network of interacting systems with many non-linear responses, and even the best-studied biological model systems have components that remain to be discovered or their functions fully characterised. This presents a significant challenge to the biological designer. Our research group is therefore interested in the application of statistical and experimental methods that facilitate forward engineering of biological systems. I will discuss the difficulties of optimising systems that encompass multiple genetic and environmental factors, expensive-to-assay responses and multiple objectives. I will introduce some of the concepts of statistical Design of Experiments - a search strategy that permits a highly efficient, multifactorial search of the biological ‘design space’. The methodology is intuitive for experimental biologists, and - importantly - it provides statistically structured data sets that enable predictive modelling. Finally, I will conclude by discussing some of our current research directions. In particular, I will discuss our efforts to embed synthetic gene networks into materials in order to provide them with additional functionality.
Dr Thomas Howard trained as a plant biochemist and molecular biologist interested in the regulation of carbon metabolism. He completed his PhD at the University of Sheffield, before working at the University of Essex and the John Innes Centre. During this time, he characterised rapid, reversible protein-protein interactions that regulate the activities of carbon-fixing enzymes, studied the movement of carbon within plants, and investigated the genetics and biochemistry of starch biosynthesis. In 2011, Dr Howard moved to the University of Exeter where his interest in carbon flux continued, accompanied by a move from a reductionist approach, to a constructionist one. Instead of dissecting metabolic pathways, he began building synthetic pathways in bacteria. His work developing metabolic pathways for the biosynthesis of petroleum-replica hydrocarbons was shortlisted for a BBSRC Innovator of the Year award. In 2015, Dr Howard moved to Newcastle University where he has established his own research group. His group’s work focuses on developing methods to facilitate building and understanding complex biological systems. In particular, he is interested in transposing useful biological traits from living systems into materials.
All welcome: bring your lunch along!
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|Dr Ali Birkett|
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