4 yr PhD Scholarship: Engineering of non-equilibrium nucleic acid circuitry for information transmission and signal processing.
We invite applications for a Royal Society-funded 4-year PhD studentship aligned with the theme of engineering sophisticated behaviour in biochemical systems. The project will be undertaken within Dr Thomas Ouldridge's "Principles of Molecular Systems" group , in close collaboration with Dr Guy-Bart Stan's "Control Engineering Synthetic Biology" group . Students interested in interdisciplinary work at the interface of biology, chemistry, physics and engineering are encouraged to apply.
Nature abounds with molecular circuits that achieve remarkable feats of information transmission and signal processing. For example, kinase enzymes transmit signals from the exterior of cells to the genomic DNA, simultaneously processing this information. The cell's response typically involves copying nucleic acid sequences into proteins, another case of information transmission. The overall effect is that the cell implements control strategies in response to complex internal and external stimuli in order to optimize behaviour. An important aspect of these systems is that they must function far from equilibrium, powered by the consumption of high free-energy molecular species [3,4,5].
The project aim is to design and construct artificial molecular analogs of these non-equilibrium signal-transmitting and signal-processing systems. Doing so will have two outcomes. Firstly, systematically exploring the operation of artificial analogs will contribute greatly to our understanding of the principles and constraints that govern natural systems, highlighting underlying biophysical and medical implications. Secondly, successful development of artificial analogs would be a major step towards implementing robust, modular and low-cost functional synthetic circuits in cells or cell-free environments, for the purpose of engineering molecular systems to give industrially or medicinally useful behaviour.
The work will involve designing, constructing and analysing analogs of natural systems from synthetic nucleic acids. The exquisite control over interactions provided by the rules of Watson-Crick base pairing will allow for systematic system design and optimisation. The same features will make the eventual designs naturally modular and engineerable, allowing the construction of more complex circuits from basic components. The work will be complemented by ongoing theoretical research within the group, as part of Dr Ouldridge's Royal Society University Research Fellowship, and other experimental projects in the Centre for Synthetic Biology.
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 transcriptional buffers, cell free extracts or 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 (email@example.com). Candidates will be considered continuously until the position is filled.
This project is funded by the Royal Society as part of the 1st year University Research Fellow Research Grant Scheme. Funding includes payment of college fees for UK/EU students and a tax-free stipend of £16,553 (reassessed annually) for four years.