Developing Novel Optofluidics Approaches for Single-Cell Sequencing - Biosciences - EPSRC DTP funded PhD Studentship Ref: 2887

About the award

This project is one of a number funded by the Engineering and Physical Sciences Research Council (EPSRC) Doctoral Training Partnership to commence in September 2018. This project is in direct competition with others for funding; the projects which receive the best applicants will be awarded the funding.

The studentships will provide funding for a stipend which is currently £14,553 per annum for 2017-2018. It will provide research costs and UK/EU tuition fees at Research Council UK rates for 42 months (3.5 years) for full-time students, pro rata for part-time students.

Please note that of the total number of projects within the competition, up to 15 studentships will be filled.

Supervisors
Dr. Stefano Pagliara
Professor Noel Morgan
Dr Sarah Richardson
Dr Fabrice Gielen

Location 
Streatham and St Lukes Campuses, Exeter

Project Description

Aim: The aim of this project is to develop novel technologies for measuring gene expression profiles in individual cells. The developed techniques will be applied to two important health problems: the analysis of persister bacterial cells linked to antibiotic resistance as well as the influence of cell clustering in the development of diabetes.

Background: The cell is the building block of life. However, despite two centuries of intense investigation, cells remain enigmatic. Thus, we have recognised a pressing need to perform single-cell studies among cell populations as opposed to standard ensemble analysis. For example, in the context of disease, a single cell can lead to tuberculosis, cancer or neurological disorders (Macaulay et al, Trends in Genetics 2017). Therefore, in order to advance our technological capabilities to investigate cells and to shed light on some of the most fundamental processes in biology it is paramount that expertise from physics and engineering is combined with that in biology and medicine.

Project: This PhD studentship will allow you to take advantage of the expertise available in Physics, Biosciences and the Medical School at Exeter to develop a novel technology platform to investigate gene expression with single-cell precision. Drs Pagliara and Gielen have recently established an experimental platform for single cell sequencing and will provide training on microfluidics, microscopy and microbiology. Prof Morgan and Dr Richardson are studying the heterogeneity among the cell populations present in islets of Langerhans to better understand the factors influencing the development of diabetes.
Specifically, you will investigate changes in the gene expression profile of single Escherichia coli bacteria and of single beta cells. On one hand, this will open the way for the investigation of the mechanisms underlying bacterial responses to antibiotic drugs which is paramount given the current antibiotic resistance crisis (Martens et al, The Journal of Antibiotics 2017).

In addition, you will begin to unravel the complexities associated with the formation of the cell aggregates which comprise the islets of Langerhans in mammals. Cells behave very differently when in close contact in 3D structures rather than when they exist as monolayers but the reasons for this are not understood. Importantly, there is also evidence that loss of the normal cellular heterogeneity occurs in islet cells during the development of diabetes and gaining a more complete understanding of this process is critical.

In order to perform gene expression profiling on single cells, you will design, fabricate and operate microfluidic devices that allow thousands of cells to be confined and manipulated, each in a tiny separate compartment (a few picoliters in volume). You will optimise the device geometry and the experimental parameters according to the cell type under investigation. You will manipulate the environment around each cell both in the bulk phase and in microfluidics, thus allowing you to study cellular responses to specific changes in the environment around the cells. Taking advantage of the microfluidic compartmentalisation you will extract RNA from individual cells and prepare it for next generation sequencing (Zilionis, Nature Protocols 2017).

You will then analyse sequencing data from single cells exposed to different environments to identify the molecular mechanisms underlying cellular response to external cues such as antibiotic exposure.  For islets of Langerhans, you will study the differentiation status of the individual endocrine cell types to establish how cell differentiation is maintained and why it may become dysregulated when islet cells lose close contact and/or are exposed to incubation conditions reminiscent of those found in patients with diabetes (e.g. elevated concentrations of glucose and free fatty acids). 

Core techniques: nanotechnology, droplet microfluidics, microscopy, cell culture, sequencing, single-cell analysis, big data analysis, microfabrication

Entry Requirements
You should have or expect to achieve at least a 2:1 Honours degree, or equivalent, in Physics, Biological sciences, Engineering, Biochemistry or Chemistry. Experience in microscopy, microfluidics, sequencing and/or cell culture is desirable.

The majority of the studentships are available for applicants who are ordinarily resident in the UK and are classed as UK/EU for tuition fee purposes.  If you have not resided in the UK for at least 3 years prior to the start of the studentship, you are not eligible for a maintenance allowance so you would need an alternative source of funding for living costs. To be eligible for fees-only funding you must be ordinarily resident in a member state of the EU.  For information on EPSRC residency criteria click here.

Applicants who are classed as International for tuition fee purposes are NOT eligible for funding. International students interested in studying at the University of Exeter should search our funding database for alternative options.

Summary

Application deadline:10th January 2018
Value:3.5 year studentship: UK/EU tuition fees and an annual maintenance allowance at current Research Council rate. Current rate of £14,553 per year.
Duration of award:per year
Contact: Doctoral Collegepgrenquiries@exeter.ac.uk

How to apply

You will be required to upload the following documents:
•       CV
•       Letter of application outlining your academic interests, prior research experience and reasons for wishing to
        undertake the project.
•       Transcript(s) giving full details of subjects studied and grades/marks obtained.  This should be an interim
        transcript if you are still studying.
•       If you are not a national of a majority English-speaking country you will need to submit evidence of your current
        proficiency in English.  For further details of the University’s English language requirements please see
        http://www.exeter.ac.uk/postgraduate/apply/english/.

The closing date for applications is midnight (GMT) on Wednesday 10 January 2018.  Interviews will be held at the University of Exeter in late February 2018.

If you have any general enquiries about the application process please email: pgrenquiries@exeter.ac.uk.
Project-specific queries should be directed to the supervisor.

During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates.  These are not limited to, but may include disclosures to:

• the selection panel and/or management board or equivalent of the relevant programme, which is likely to include staff from one or more other HEIs;
• administrative staff at one or more other HEIs participating in the relevant programme.

Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.