Red blood cells and phagocytosis: how the immune system sorts new cells from old.PhD in Mathematics (GW4 BioMed MRC DTP) Ref: 3640
About the award
Dr David Richards, Department of Mathematics, Living Systems Institute, University of Exeter
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-up 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 environmental-controlled 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.
This studentship is funded through GW4 BioMed MRC Doctoral Training Partnership. It consists of full UK/EU tuition fees, as well as a Doctoral Stipend matching UK Research Council National Minimum (£15,009 for 2019/20, updated each year) for 3.5 years.
For further information relating to the funding please see the main MRC GW4 BioMed website
This project is in competition with 88 other projects across the partnership; up to 18 studentships in total will be available.
Eligibility and Residency Requirements
To be eligible for a full award (fees and stipend) from a Research Council, a UK or EU student must have no restrictions on how long they can stay in the UK and have been ordinarily resident in the UK for at least 3 years prior to the start of the studentship.
An EU student who has not been resident in the UK for at least 3 years prior to the start of the studentship is generally eligible for a fees-only award from the Research Council: to be eligible for a fees-only award, a student must be ordinarily resident in a member state of the EU; in the same way as UK students must be ordinarily resident in the UK.
For our regular recruiting round, the Doctoral Training Partnership has additional funding from the partner universities to support a limited number of EU students who do not meet the UK residency requirements, so long as they meet the criteria for a fees-only award: these studentship will therefore be fully funded (fees and stipend).
For full details on eligibility, please refer to the MRC GW4 BioMed website
Students with 'International' status are unfortunately not eligible to apply.
If you are applying for a place on a collaborative programme of doctoral training provided by Cardiff University and other universities, research organisations and/or partners please be aware that your personal data will be used and disclosed for the purposes set out below.
Your personal data will always be processed in accordance with the General Data Protection Regulations of 2018. Cardiff University (“University”) will remain a data controller for the personal data it holds, and other universities, research organisations and/or partners (“HEIs”) may also become data controllers for the relevant personal data they receive as a result of their participation in the collaborative programme of doctoral training (“Programme”).
For further information regarding data protection for the Application Process and if you become a student on one of the Programmes please click here
For an overview of the MRC GW4 BioMed progamme, 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, and can fund additional training, including Masters to assist discipline conversion. 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.
If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.5 in any section) by the start of the programme.
How to apply
Applications Open on 29 September and close at 17:00 on Monday 25 November 2019
You will need to complete an application to the GW4 BioMed MRC DTP for an 'offer of funding'
Applying for an 'offer of funding'
Please complete the application form at https://www.gw4biomed.ac.uk/doctoral-students/ by 5pm Monday 25 November 2019.
The Research Theme Panels will complete the shortlisting and will aim to inform applicants by Thursday, 19 December 2019. If you are shortlisted you will need to:
- contact the lead supervisor of you chosen project in which you are interested, to arrange an informal interview (which can be in person, by telephone or by Skype) between 3 and 15 January 2020. Please note that interview expenses will not be available for candidates to attend these meetings.
- attend a formal interview, with a panel of four academics which will take place in Cardiff on 21 and 22 January 2020.
For further details of the application process please see the following web page www.gw4biomed.ac.uk/doctoral-students/
You do NOT need to apply to the University of Exeter at this stage - only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Exeter.
|Application deadline:||25th November 2019|
|Value:||Stipend matching UK Research Council National Minimum (£15,009 p.a. for 2019/20, updated each year) plus UK/EU tuition fees|
|Duration of award:||per year|
|Contact: PGR Recruitmentfirstname.lastname@example.org|