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Engineering minimal molecular replicators


   Department of Bioengineering

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  Dr Thomas Ouldridge  Applications accepted all year round  Funded PhD Project (Students Worldwide)

About the Project

We invite applications for a Royal Society-funded 4-year PhD studentship, "Engineering minimal molecular replicators". The experimental project will be undertaken within Dr Thomas Ouldridge's "Principles of Molecular Systems" group [1] within the Department of Bioengineering at Imperial College London. Students interested in interdisciplinary work at the interface of biology, chemistry, physics and engineering are encouraged to apply. Applications from non-UK students are welcomed. 

The replication of a genetic code is arguably the most important molecular signature of life on Earth, and the importance of polymer-based replication in nature makes the construction of minimal synthetic replicators a key research goal. Firstly, building synthetic self-replicating polymers would be an important step towards creating artificial life, an enormous scientific achievement. Secondly, self-replicating systems are at the heart of nature’s extraordinary ability to generate chemical complexity; synthetic analogues would be an alternative engineering platform for the development of novel chemistry over which researchers would have a much tighter degree of control. Thirdly, the process of engineering minimal synthetic replicators, in which key components are rationally designed from the bottom up, would teach us a great deal about the basic physical principles of this crucial process. 

Despite the significance of polymer-based replication, researchers have had limited success in recreating it in minimal settings without using highly-evolved enzymes. The basic obstacle is product inhibition: it is relatively straightforward to assemble a complementary sequence on a polymer template, but the product then tends to stay stuck, bound to the template via cooperative bonds, inhibiting repeated rounds of replication. Dr Ouldridge's group have developed a new DNA-based reaction mechanism with the potential to circumvent this problem [2]. The aim of this PhD will be to adapt that mechanism to the context of replication, and demonstrate the sequence-specific replication of dimeric, trimeric and longer templates. 

The work will involve designing, constructing and analysing synthetic nucleic acid-based systems. The exquisite control over interactions provided by the rules of Watson-Crick base pairing will allow for systematic system design and optimisation. The work will be complemented by ongoing theoretical and simulation-based projects within the group, as part of Dr Ouldridge's Royal Society University Research Fellowship. Candidates from a wide range of backgrounds, with a degree in engineering, physical or life sciences, will be considered. However, experience in a wet lab is essential, and a track record of implementing molecular reactions in vitro is highly desirable. Prior work with nucleic acids would be beneficial.

To apply for this position, please email a single PDF file including: a (1 page max) cover letter describing your interests and research experience, a CV detailing academic performance (including grades/marks) and names and contact information of two referees, to Dr Thomas Ouldridge (). Candidates will be considered continuously until the position is filled, with an initial shortlisting on 11th Feb 2022. 


Funding Notes

This project is funded by the Royal Society and the Department of Bioengineering at Imperial College London. Funding includes payment of college fees (including international fees, where relevant) and a tax-free stipend of £17,609 (reassessed annually) for four years.

References

References
[1] http://www.imperial.ac.uk/principles-of-biomolecular-systems/
[2] https://pubs.acs.org/doi/10.1021/acsnano.0c10068

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