Model-driven design of minimal genomes

Lead Research Organisation: University of Bristol
Department Name: Biological Sciences

Abstract

The advent of genome sequencing, genome editing and the ability to create synthetic genomes has spurred interest in minimal/reduced genomes. Finding minimal genomes should help us to understand relationships between genotype and phenotype, predict the effects of changes and, ultimately, design synthetic organisms.

While progress has been made in editing and creating genomes, very little has been made in rationally designing minimal genomes. Current methods for predicting minimal genomes compare essential gene sets (PNAS, 93, 10268-73, 1996) or disrupt single genes (Sciences, 286, 2165-69, 1999). Both approaches have been shown to be potentially misleading due to the complexity of the genotype to phenotype relationship (Nature, 407, 757-62, 2000).

I will develop robust and predictive methods for genome reduction, taking advantage of advances in computer models of both Escherichia coli (Nature protocols, 2, 727-38, 2007) and Mycoplasma genitalium (Cell, 150, 389-401, 2012). Such models have increased predictive powers but there is still a significant gap between computational predictions and experimental results.

I will mainly work on the experimental aspects of the project, involving characterisation of multiple in-vivo genetic disruptions in E. coli and Syn2.0/3.0. Resulting data will be used to quantify the accuracy of in-silico gene knockout models, refine them and discover reduced genomes.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
EP/N509619/1 01/10/2016 30/09/2021
1793989 Studentship EP/N509619/1 19/09/2016 31/03/2020 Joshua Rees Rees