Characterisation of canine erythropoiesis at the University of Edinburgh

Supervisors: Dr Douglas Vernimmen (UoE), Prof Jan Frayne (University of Bristol) and Prof Lesley Forrester (CRM, UoE)

Closing Date:  5th January 2022

The PhD project will establish an erythroid differentiation system for canine erythroid cells from CD34+ stem cells from healthy donors obtained at the R(D)SVS, based on the highly efficient human system but with modifications as required to optimize for canine cells. They will also create a canine erythroid cell line based on the highly successful and invaluable human erythroid lines (Trakarnsanga et al., 2017; Trakarnsanga 2020; Daniels et al., 2021), for the study of canine erythropoiesis in health and disease, and as demonstration of a potential diagnostic and therapeutic tool.

The student will compare regulation of erythroid cell differentiation in canine and human (human erythroid differentiation is well studied and characterized) for both the CD34+ cultures and the canine line, comparing the latter with the extensively characterized human erythroid cell line. This will require a range of standard molecular biology and biochemical techniques to identify key regulatory proteins as well as global techniques such as RNAseq and comparative proteomics to obtain a comprehensive analysis of how gene expression etc changes during the dynamic differentiation process. This will also allow identification of key marker proteins for monitoring canine erythroid cell differentiation by multiplex flow cytometry. For human erythroid cells this technique is used to evaluate differentiation in both normal and disease erythroid cells using blood group antigens, but these differ in the dog. Establishment of such systems for canine erythroid cell differentiation will be valuable for evaluating cause and status of anaemia in dogs.

References

Trakarnsanga, K., Griffiths, R.E., Wilson, M.C., Blair, A., Satchwell, T.J., Meinders, M., Cogan, N., Kupzig, S., Kurita, R., Nakamura, Y. et al. (2017) An immortalized adult human erythroid line facilitates sustainable and scalable generation of functional red cells. Nat Commun, 8, 14750.

Trakarnsanga K, Tipgomut C, Metheetrairut C, Wattanapanitch M, Khuhapinant A, Poldee S, Kurita R, Nakamura Y, Srisawat C, Frayne (2020). Generation of an immortalised erythroid cell line from haematopoietic stem cells of a haemoglobin E/β-thalassemia patient.J.Sci Rep. 2020, 10,16798.

Daniels DE, Ferguson DCJ, Griffiths RE, Trakarnsanga K, Cogan N, MacInnes KA, Mordue KE, Andrienko T, Ferrer-Vicens I, Ramos Jiménez D, Lewis PA, Wilson MC, Canham MA, Kurita R, Nakamura Y, Anstee DJ, Frayne (2021). Reproducible immortalization of erythroblasts from multiple stem cell sources provides approach for sustainable RBC therapeutics.J.Mol Ther Methods Clin Dev,12, 22:26-39. 

Funding information and application procedures

We would encourage applicants to list up to three projects of interest (ranked 1st, 2nd and 3rd choice) from those listed with a closing date of 5th January 2022 at https://www.ed.ac.uk/roslin/work-study/opportunities/studentships 

This opportunity is open to UK and international students and provides funding to cover stipend, tuition fees and consumable/travel costs.  Applications including a statement of interest and full CV with names and addresses (including email addresses) of two academic referees, should be emailed to [email protected].

When applying for the studentship please state clearly the project title/s and the supervisor/s in your covering letter.

A webinar will be held on Tuesday 14th December at 13.00hrs (UK time) to assist you in the application process and tell you a little more about studying for a PhD with us.  It will also give you an opportunity to ask any questions you may have.  If interested in joining us please send your name and email address to [email protected]by Friday 10th December and we will send you a link to the on line meeting

ALL APPLICATION PROCEDURES MUST BE COMPLETED BY THE CLOSING DATE 5th JANUARY 2022