Phagocytosis and red blood cells: sorting new cells from old, Mathematics PhD Studentship, (MRC GW4 BioMed DTP funded) Ref: 3948
About the award
Dr David Richards, College of Engineering, Mathematics and Physical Sciences, Living Systems Institute, University of Exeter
Dr Charlie Jeynes, Centre for Biomedical Modelling and Analysis, University of Exeter.
Professor Karen Edler, Chemistry, University of Bath.
Dr Ashley Toye, Biomedical Sciences, University of Bristol
Background: Clearance of old red blood cells (RBCs) is essential for correct physiological maintenance of the blood. However, detailed mechanisms of this process remain a mystery, and it is unclear how RBCs "know" how old they are, and how this affects phagocytosis.
Understanding this process is critical as premature RBC ageing and abnormal clearance is relevant to a range of common medical conditions such as sickle-cell anaemia, hemoglobinopathies, Gaucher's disease, chronic kidney disease, diabetes and parasite infections. The approach: Often the quickest way to make progress with this type of problem is to intimately combine experiments and modelling. Here, this will involve imaging phagocytosis of RBCs in the lab (with time-lapse microscopy of both real and artificial RBCs) and designing mathematical models (based on the immune cell shape and RBC stiffness).
This combination means that the experiments can directly inform the model and that the modelling can suggest novel experimental directions. This approach will allow the student to learn a highly-desirable combination of modelling and experimental skills, leading to excellent future career prospects. Project plan: This cross-disciplinary studentship will be based at Exeter University but will also involve spending time at both Bristol University and Bath University, meaning the student will spend time in three separate labs at three separate institutes. The student will also join the growing GW4 NanoMedicine network that the PIs have recently set-u using a GW4 Initiator Award (see https://www.gw4nanomedicine.com/).
The project itself will include:
1. Phagocytic assays. The engulfment of plastic beads will be examined to determine the role of target stiffness
and coating on the efficiency and rate of phagocytic uptake. This will involve using a dual-micropipette system and an environmentalcontrolled Leica microscope. The student will also use our brand new state-of-the-art NanoSight microscope.
2. Modelling. A mathematical/computational model that involves membrane shape, receptor dynamics and intracellular signalling will be designed. This will be based on a published phagocytosis model recently developed by the Richards group. For the first time, this model will involve the role of target stiffness, which is critical for understanding RBC clearance.
3. Design and culture of RBCs. Erythrocyte lines that overexpress CD47 (a "don't eat me" signal) will be developed in Dr Toye's lab in Bristol, before moving on to isolate primary white cells and utilise macrophage and neutrophil culture models. Cells with a range of deformabilities will be designed by altering membrane and cytoskeleton composition.
4. Image analysis. Building on existing custom-built software within the Richards group, image analysis software will be developed that automatically interprets the time-lapse images of phagocytosis, focusing on the rate of engulfment and the phagocytic cup shape. This part will also be based on a novel imaging-analysis system recently developed in Bristol by the Toye lab.
5. Properties of RBCs. Cultured RBCs under- or overexpressing CD47 will be characterised (e.g. for turgidity, stiffness and membrane tension) with a variety of biophysical measures in Prof Edler's and Dr Toye's labs (e.g. using an automated rheoscope). Outreach: Public involvement will also play an important part of this studentship.
The student will work directly with Dr Silvia Bortoli (the Communities Engagement Manager within the Centre for Biomedical Modelling and Analysis at Exeter University) and the MAGPIEs (a group of lay people involved in medical research) in order to disseminate results and guide research. Drs Jeynes and Richards are already heavily involved with this programme.
A GW4 BioMed MRC DTP studentship includes full tuition fees at the UK/Home rate, a stipend at the minimum UKRI rate, a Research & Training Support Grant (RTSG) valued between £2-5k per year and £300 annual travel and conference grant based on a 3.5-year, full-time studentship.
These funding arrangements will be adjusted pro-rata for part-time studentships.
Throughout the duration of the studentship, there will be opportunities to apply to the Flexible Funding Supplement for additional support to engage in high-cost training opportunities.
GW4 BioMed MRC DTP studentships are available to UK or non-UK applicants. Students considered International for tuition fee purposes are eligible to apply for these studentships but should note that they may have to pay the difference between the home UKRI fee and the institutional International student fee. The fee schedule for Exeter can be found on the following web page https://www.exeter.ac.uk/pg-research/money/fees/.
We will update applicants when further information becomes available.
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For an overview of the MRC GW4 BioMed programme please see the website www.gw4biomed.ac.uk
In addition to those with traditional biomedical or psychology backgrounds, the DTP welcomes students from non-medical backgrounds, especially in areas of computing, mathematics and the physical sciences. Further training can be provided to assist with discipline conversion for students from non-medical backgrounds.
Applicants for a studentship must have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an area appropriate to the skills requirements of the project. Applicants with a Lower Second Class degree will be considered if they also have a Master’s degree or have significant relevant non-academic experience.
English Language Requirements
If English is not your first language, you will need to have achieved at least 6.5 in IELTS (and no less 6.5 in any section) by the start of the programme. Please refer to the English Language requirements web page for further information.
How to apply
Applications open 21 September 2020 and close at 17:00 on 23rd November 2020
To begin a GW4 BioMed MRC DTP studentship, applicants must secure an offer of funding from the DTP.
Stage 1: Applying to the DTP for and Offer of Funding
1. Select your projects from the project descriptions available on this website. You may select up to three projects in your application.
2. Submit your application using this online form before 5 pm on Monday, 23 November 2020.
3. Student shortlisting is conducted in a blind review of studentship applications by theme-specific panels. Up to 60 top candidates who emerge from this deliberation will be invited to interview.
4. Informal, virtual meetings will be arranged by the successfully shortlisted candidates with the lead supervisors of each project to which they have applied before the formal interview.
5. Formal interviews will occur virtually by theme-specific panels including representatives from each GW4 institution on 20-21 of January 2021.
6. Student selection for up to 17 funded studentships occurs after the formal interviews. Projects are allocated based on the rank of the successful candidates, therefore, it is not always possible to offer an applicant their first-choice project.
7. A clearing period will follow until approximately mid-March until all places have been offered and accepted. For this reason, it is not possible to provide immediate interview results to shortlisted applicants.
Stage 2: Applying to the lead institution for an Offer of Study
Once you have been offered a studentship with the GW4 BioMed MRC DTP, you will need to apply for an Offer of a Place at the home institution of your lead supervisor. Please note that each institution has different application processes.
Applicants for projects based at the University of Exeter should apply to the DTP first to secure an offer of funding. Once an offer of funding is issued by the DTP, you will receive more information on submitting a formal application to the relevant institution, guided by the DTP and local admin contacts.
Written application forms will be evaluated against the following criteria:
Proven academic quality: normally evidenced by an excellent performance to first degree and/or Master’s level but may also be demonstrated by a record of relevant professional practice.
Research potential: evidenced through their supporting statement and supported by performance in research projects at first degree and/or Master’s level, or another form of dedicated preparation for research.
Personal motivation & commitment: evidenced through their supporting statement, by their enthusiasm for the project area and how they see it relating to their career goals.
Non-biomedical disciplines: In line with supporting interdisciplinary and quantitative skills, special consideration will be given by the interview panels to non-biomedical applicants. Such candidates should not feel the selection criteria are biased towards biomedical applicants as their unique skills will be taken into account.
Candidates selected to interview will be evaluated against the following criteria:
Critical thinking assessed via discussion of a student-selected piece of data
Fit with the project: The interview panel will evaluate the candidate’s aptitude and understanding of the key issues in the project, supported by feedback from informal meetings with the potential lead supervisor.
Personal commitment & motivation
If you have any queries about the GW4 BioMed MRC DTP or about applying for an Offer of Funding, you can get in touch with the DTP Team by emailing GW4BioMed@cardiff.ac.uk.
If you have any questions about applying for an Offer to Study, you can get in touch with the administrative team via email@example.com
|Application deadline:||23rd November 2020|
|Value:||Stipend matching UK Research Council National Minimum (£15,285 p.a. for 2020/21, updated each year) plus UK/Home tuition fees|
|Duration of award:||per year|
|Contact: PGR Admissions Officefirstname.lastname@example.org|