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Cell Deformation Uptake for Quantum Dot based Biosensors

PGR-P-1094

Key facts

Type of research degree
PhD
Application deadline
Wednesday 1 March 2023
Project start date
Sunday 1 October 2023
Country eligibility
International (open to all nationalities, including the UK)
Funding
Competition funded
Source of funding
University of Leeds
Supervisors
Dr Kevin Critchley and Professor Stephen Evans
Additional supervisors
Prof Steve Evans
Schools
School of Physics and Astronomy
Research groups/institutes
Molecular and Nanoscale Physics
<h2 class="heading hide-accessible">Summary</h2>

This project is part of a bigger project in which a team of researchers will be developing new methods of reprogramming cells to produce induced pluripotent stem cells. To achieve this, we are engineering a microfluidic device which uses hydrodynamic forces to momentarily stretch each cell, one by one, in a highly controlled manner. This stretching causes pores to form in the membrane which then allows us to insert the necessary ingredients through diffusion, without complicated delivery vehicles. The precision and control by which this is performed will offer advantages over the current methodologies and will improve the yield and time it takes to reprogramme sufficient cell numbers, which would have practical applications in the clinic or research laboratory. In this PhD project your aim will be to advance nano-optical reporters, that can report whether the iPSCs are under oxidative (or reductive) stress. The nano-reporters developed to do this role will enter the cells in the same manner as the RNA using the microfluidic device and will be analysed by fluorescence spectroscopy. <br /> <br /> The biosensors we will be made by modifying quantum dots (Qdots) to develop a fluorescent assay for the selective monitoring redox balance inside cells. Qdots are semiconducting nanoparticles with tuneable fluorescent properties. The broad excitation band of the Qdots, high extinction coefficient, as well as the fact they do not suffer from photobleaching (like organic fluorescent dyes) makes them excellent compounds for imaging. Typically, the semi-conducting 'core' (e.g. CdSe) of a Qdot is embedded inside an inorganic 'shell' (e.g. ZnS) that protects the core and enhances fluorescent properties. The outer ZnS shell can modified with a second organic shell, which provides the Qdot with desirable biological properties, such as solubility in aqueous media, selective binding against a biological target or enhanced uptake by cells. For this proposal, an important property of Qdots is the fact that its fluorescence intensity is dependent on the presence of electron acceptors (or holes) in the near vicinity. This property has rarely been employed for redox sensing and, so far, only by adsorbing small organic redox compounds on the Qdot. In this project, we aim to utilise the redox-sensitivity of Qdots to create a sensor that can selectively measure the redox balance inside cells.<br />

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

<p style="text-align:justify">Cell therapy is one of the fastest growing technologies in the field of medicine. The principle, is that cells can be taken from a patient, modified, and then placed back in the patient to perform a role for recovering functions or fighting diseases. The technique is powerful because the cells are from the patient, the implanted cells are not foreign bodies and are therefore not attacked by their own immune system. Stem cells are an ideal cell type, as these have the potential to differentiate into any cell type in the body. So where can we obtain these stem cells? There are embryonic stem cells are pluripotent (they can divide into more stem cells or differentiate) and adult stem cells. embryonic stem cells are politically and ethically highly controversial. Adult stem cells can be found in most adults, but only in small numbers and appear to be more limited in their ability to differentiate to any cell type. In 2006, it was discovered that any cell that is not a sperm or an egg cell, can be reprogrammed to generate induced pluripotent stem cells (iPSCs). These offer the potential to realise cell therapy as a common technique used in the clinic. However, generating the iPSCs quickly and safely remains a challenge to more wide scale applications and trials.</p> <p>In this project, we are engineering a microfluidic device which will significantly improve the yield of reprogrammed cells. The device flows cells through a channel and uses hydrodynamic forces to momentarily stretch each cell, one by one, in a highly controlled manner. This stretching causes pores to form in the membrane which then allows us to insert the necessary ingredients (RNA) through diffusion, without complicated delivery vehicles. The precision and control by which this is performed will offer advantages over the current methodologies and will improve the yield and time it takes to reprogramme sufficient cell numbers, which would have practical applications in the clinic or research laboratory. The proposal also aims to advance nano-optical reporters, that can report whether the iPSCs are under oxidative (or reductive) stress. The nano-reporters developed to do this role will enter the cells in the same manner as the RNA using the microfluidic device and will be analysed by fluorescence spectroscopy.</p> <p>To achieve these goals the microfluidics will need to be optimised to enhance the update of RNA for the reprogramming. We will make use of the rapid microfluidic prototyping laboratory in physics, where we do all aspects of the fabrication, meaning that fine adjustments can be realised in a relatively short time. Our highly disciplinary team includes expertise in stem cells (based at the St James&rsquo;s hospital campus), and they are any to both evaluate and adjust the biological parameters to obtain the best cell reprogramming yields on &lsquo;easy to transfect&rsquo; cells and then translate that knowledge to more challenging patient derived samples. While the reprogramming is being optimised, we will also be synthesizing and testing dual emitting quantum dots which will fluorescently indicate the redox potential inside cell (indicator of the cell health).</p> <p style="text-align:justify">&nbsp;</p> <p>&nbsp;</p>

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

<p>Formal applications for research degree study should be made online through the&nbsp;<a href="https://www.leeds.ac.uk/research-applying/doc/applying-research-degrees">University&#39;s website</a>. Please state clearly in the Planned Course of Study that you are applying for <em><strong>PHD Physics &amp; Astronomy FT</strong></em> and&nbsp;in the research information section&nbsp;that the research degree you wish to be considered for is <em><strong>Microfluidic Deformation for Intracellular Delivery</strong></em> as well as Dr&nbsp;Kevin Critchley 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 style="margin-bottom:11px"><em>As an international research-intensive university, we welcome students from all walks of life and from across the world. We foster an inclusive environment where all can flourish and prosper, and we are proud of our strong commitment to student education. Across all Faculties we are dedicated to diversifying our community and we welcome the unique contributions that individuals can bring, and particularly encourage applications from, but not limited to Black, Asian, people who belong to a minority ethnic community, people who identify as LGBT+ and people with disabilities. Applicants will always be selected based on merit and ability.</em></p> <p class="MsoNoSpacing">Applications will be considered on an ongoing basis. &nbsp;Potential applicants are strongly encouraged to contact the supervisors for an informal discussion before making a formal application. &nbsp;We also advise that you apply at the earliest opportunity as the application and selection process may close early, should we receive a sufficient number of applications or that a suitable candidate is appointed.</p> <p>Please note that you must provide the following documents in support of your application by the closing date of 1 March 2023:</p> <ul> <li>Full Transcripts of all degree study or if in final year of study, full transcripts to date</li> <li>Personal Statement outlining your interest in the project</li> <li>CV</li> <li>Funding information including any alternative sources of funding that you are applying for or if you are able to pay your own fees and maintenance</li> </ul>

<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. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

<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. Some schools and faculties have a higher requirement.

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

<p style="margin-bottom:12px"><strong>Self-Funded or externally sponsored students are welcome to apply.</strong></p> <p><strong>UK</strong>&nbsp;&ndash;&nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/209-leeds-doctoral-scholarships-2022">Leeds Doctoral Scholarships</a> and <a href="https://phd.leeds.ac.uk/funding/234-leeds-opportunity-research-scholarship-2022">Leeds Opportunity Research Scholarship</a> are available to UK applicants. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP).&nbsp; <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Non-UK</strong> &ndash; The&nbsp;<a href="https://phd.leeds.ac.uk/funding/102-bell-burnell-scholarship-award-awarded-by-the-iop">Bell Burnell Scholarship Award</a>&nbsp;is available to support applicants who are from groups that are currently under-represented in physics (awarded by the IOP).&nbsp; &nbsp;The&nbsp;<a href="https://phd.leeds.ac.uk/funding/48-china-scholarship-council-university-of-leeds-scholarships-2021">China Scholarship Council - University of Leeds Scholarship</a>&nbsp;is available to nationals of China. The&nbsp;<a href="https://phd.leeds.ac.uk/funding/73-leeds-marshall-scholarship">Leeds Marshall Scholarship</a>&nbsp;is available to support US citizens. <a href="https://phd.leeds.ac.uk/funding/60-alumni-bursary">Alumni Bursary</a> is available to graduates of the University of Leeds.</p> <p><strong>Important:&nbsp;</strong> Any costs associated with your arrival at the University of Leeds to start your PhD including flights, immigration health surcharge/medical insurance and Visa costs are not covered under this studentship.</p> <p>Please refer to the <a href="https://www.ukcisa.org.uk/">UKCISA</a> website for information regarding Fee Status for Non-UK Nationals.</p>

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

<p>For further information about this project, please contact Dr Kevin Critchley<br /> e: <a href="mailto:EMAIL@leeds.ac.uk">k.critchley@leeds.ac.uk</a></p> <p>For further information about your application, please contact Doctoral College Admissions<br /> e:&nbsp;<a href="mailto:maps.pgr.admissions@leeds.ac.uk">maps.pgr.admissions@leeds.ac.uk</a></p>