Investigation and Development of a Whole-Cell Model for a Minimal Synthetic Organism

Lead Research Organisation: University of Bristol
Department Name: Engineering Mathematics

Abstract

A signicant focus in the Synthetic Biology eld has recently been investigating minimal genomes. As
of 2016, the smallest genome is that of Mycoplasma mycoides JCVI-syn3.0, which is a synthetic bacterium
derived from Mycoplasma mycoides | selected for the genome-minimisation project because it grows fast,
so the turnaround of replication is ecient. Genetic material was removed from the genome according
to a set of rules devised by the scientists, in an attempt to locate and remove all of the non-essential
genetic material. Of the 901 mycoplasma genes, 428 were removed, but 31% of the `essential' genes have
unknown functions, so there is still work to be done in unravelling their role in the genome. Currently, a
lot of the minimising genome work has been trial-and-error, due to lack of knowledge about the function
of certain genes and the necessity of some genetic information, so algorithms that could analyse genomes
and isolate surplus genetic material would be hugely useful in this area. This would also contribute
towards simplifying whole-cell models. Bioinformatics is a useful tool that can indicate the function of
genetic material by nding genes though data analysis | going some way to deciphering genetic code.
The research that I am proposing is a continuation of the minimising genome work. Currently, there
is a working MATLAB model that simulates Mycoplasma genitalium, which consist of 28 submodels
for di erent cell processes that are integrated together. Appropriate mathematical methods are used for
each process, such as ux-balance analysis for metabolism, and Poisson processes for protein degradation.
Given the scale of the model, running and processing requires a lot of time and there are large amounts
of output data. Additionally, the models are only useful for the analysis of simple organisms, but there is
opportunity to develop models for other unicellular organisms; for example JCVI-syn3.0. These can be
used to predict the impact that deletion of certain genes will have on the cell function, which eventually
may indicate which genes are superfluous to the survival of the cell, and demonstrate which genes are the
basic requirements for life. Also, this can be veried in lab work, where genetic material is removed from
living cells to see if they flourish or not. The information could then be applied to design new synthetic
organisms possessing desired functions.

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
1953789 Studentship EP/N509619/1 18/09/2017 31/07/2021 Sophia Landon