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Switchable molecules for information processing


Project Description

In this project you will develop fundamental understanding of how arrays of electrodes can be used to switch molecules controllably and thereby provide on-demand access to e.g. DNA sequences that can be used as instructions for computational tasks. A range of novel experiments will be carried out, including the construction of microfluidic systems to generate highly localised electrochemical pH changes, and of electrochemical circular dichroism experiments to understand the conformational behaviour of pH-modulated molecules.

DNA computing, in which interacting DNA molecules are exploited to solve a computationally expensive problem, was pioneered by Adelman over two decades ago [1]. Since then, significant progress has been made and logic gates [2,3], neural networks [4], finite state machines [5,6] and many other computational tools have been demonstrated and implemented using DNA. However, DNA-based information processing systems (IPSs) are primarily (re)programmed through the addition of new DNA oligonucleotides that represent additional information, such as processing instructions or a specific molecular address for random access of a DNA memory. Recent work has shown that DNA complexes can be designed to be pH-sensitive such that they alter between stable conformations when subjected to pH changes – we have recently investigated an example of such a DNA system made from a partly double and partly single-stranded DNA molecule. At neutral or slightly acidic pH, the single-stranded DNA folds onto the double-stranded portion to form a triple-stranded DNA domain, stabilized by Hoogsten base-pairing. In contrast, at basic pH the triplex becomes destabilized to expose the DNA bases encoded within the single-stranded domain. Critically, switching between single strand and triplex is a reversible process, achieved through pH cycling.

In other work [6] it was demonstrated that although open, single-stranded DNA loops can base-pair with complementary single-stranded DNA, closed loops cannot and therefore prevent hybridization. Therefore, in the context of an IPS, the sequence of DNA within the loop domain can be viewed as instructions that can be revealed and concealed on demand – in pH switchable systems via a small change in pH. If the DNA constructs are proximal to electrodes, pH changes can be achieved locally via electrochemical hydrolysis of the aqueous electrolyte. Importantly, this will provide a potential route for interfacing traditional electronic ISPs and DNA-based (solution-phase) ISPs.

However, the behaviour of the DNA complexes upon pH-modulation, and in particular their conformational changes, need to be understood in detail such that an array of pH switchable systems can be designed and appropriate conditions for robust electrochemical switching can be identified. This is the focus of this PhD project.

Funding Notes

UK/EU/International  – School of Electronic and Electrical Engineering Scholarship Award paying Academic Fees at Home/EU fee rate (£4,600 in Session 2020/21) or International fee rate (£23,750 in Session 2020/21) and Maintenance matching EPSRC rates (£15,285 in Session 2020/21) per year for 3 years.  Funding is awarded on a competitive basis.

References

1. Adleman LM Science 266, 1021–1024 (1994)
2. Seelig G et al Science 314, 1585–1588 (2006)
3. Stojanovic MN et al JACS 124, 3555–3561 (2002)
4. Qian L et al Nature 475 (7356), 368–372 (2011)
5. Benenson Y et al Nature 414, 430–434 (2001)
6. Costa Santini C et al Chem. Commun. 49(3), 237–239 (2013)

Related Subjects

How good is research at University of Leeds in General Engineering?

FTE Category A staff submitted: 44.80

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