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Switchable molecules for information processing

PGR-P-720

Key facts

Type of research degree
PhD
Application deadline
Friday 17 April 2020
Project start date
Thursday 1 October 2020
Country eligibility
International (open to all nationalities, including the UK)
Funding
Funded
Source of funding
University of Leeds
Supervisors
Professor Christoph Walti and Dr Christopher Wood
Schools
School of Electronic and Electrical Engineering
Research groups/institutes
Pollard Institute
<h2 class="heading hide-accessible">Summary</h2>

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.

<h2 class="heading hide-accessible">Full description</h2>

<p>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 &ndash; 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.</p> <p>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 &ndash; 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.</p> <p>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.</p> <h5>References</h5> <ol> <li>Adleman LM <em>Science</em> <strong>266</strong>, 1021&ndash;1024 (1994)</li> <li>Seelig G et al <em>Science</em> <strong>314</strong>, 1585&ndash;1588 (2006)</li> <li>Stojanovic MN et al <em>JACS </em><strong>124, </strong>3555&ndash;3561 (2002)</li> <li>Qian L et al <em>Nature</em> <strong>475 (7356)</strong>, 368&ndash;372 (2011)</li> <li>Benenson Y et al <em>Nature</em> <strong>414</strong>, 430&ndash;434 (2001)</li> <li>Costa Santini C et al <em>Chem. Commun.</em> <strong>49(3)</strong>, 237&ndash;239 (2013)</li> </ol>

<h2 class="heading">How to apply</h2>

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://eps.leeds.ac.uk/electronic-engineering-research-degrees/doc/apply">University&#39;s website</a>. Please state clearly in the research information section&nbsp;that the research degree you wish to be considered for is &ldquo;Switchable molecules for information processing&rdquo; as well as <a href="https://eps.leeds.ac.uk/electronic-engineering/staff/337/dr-chris-wood">Dr Christopher Wood</a> as your proposed supervisor.</p> <p>If English is not your first language, you must provide evidence that you meet the University&#39;s minimum English language requirements (below).</p> <p><em>We welcome applications from all suitably-qualified candidates, but UK black and minority ethnic (BME) researchers are currently under-represented in our Postgraduate Research community, and we would therefore particularly encourage applications from UK BME candidates. All scholarships will be awarded on the basis of merit.</em></p>

<h2 class="heading heading--sm">Entry requirements</h2>

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline.

<h2 class="heading heading--sm">English language requirements</h2>

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid.

<h2 class="heading">Funding on offer</h2>

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

<h2 class="heading">Contact details</h2>

<p>For further information please contact Doctoral College Admissions,<br /> e: <a href="mailto:phd@engineering.leeds.ac.uk">phd@engineering.leeds.ac.uk</a>, t: +44 (0)113 343 5057</p>


<h3 class="heading heading--sm">Linked funding opportunities</h3>
<h3 class="heading heading--sm">Linked research areas</h3>