Decoding blood formation: exploring the hidden pathways from stem cells to platelets

Blood clotting is an essential response to injury and is crucial for survival. Platelets are the cells responsible and need to be produced at an astonishing rate of 1 trillion cells per hour to maintain this function. Failure to do so can be life threatening and is a frequent issue in the elderly, cancer patients, and people with autoimmune diseases. 

Unfortunately the mechanism of platelet production is poorly understood. To identify treatments for platelet shortages it is vital to first understand their production. Previous work in our group has shown that there are 2 stem cell types, one that produces a lot of platelets and the other only a small number.

This project will investigate the molecular differences between stem cells that produce high and low numbers of platelets. To achieve this the student will employ cutting-edge FACS cell isolation, single-cell RNA sequencing, lineage tracing, synthetic biology, and bioinformatic techniques established in the Wojtowicz and Haerty groups.

The project will be based in the Wojtowicz group, but will collaborate closely with the Haerty and Beraza (Quadram Institute) groups.

This will give you a strong and experienced supervisory team with expertise in single cell and computational methods. 

Established collaborations with pharmaceutical companies will allow the student to translate their findings into industry. The student will have access to extensive training and career development opportunities at EI, QIB, and as part of the Norwich Biosciences Doctoral Training Partnership.

Further reading:

• Wojtowicz, E. E. et al. Panhematopoietic RNA barcoding enables kinetic measurements of nucleate and anucleate lineages and the activation of myeloid clones following acute platelet depletion. Genome Biol 24, 152 (2023). https://doi.org/10.1186/s13059-023-02976-z
• Wojtowicz EE, Lechman ER, Hermans KG, Schoof EM, Wienholds E, Isserlin R, van Veelen PA, Broekhuis MJ, Janssen GM, Trotman-Grant A, Dobson SM, Krivdova G, Elzinga J, Kennedy J, Gan OI, Sinha A, Ignatchenko V, Kislinger T, Dethmers-Ausema B, Weersing E, Alemdehy MF, de Looper HW, Bader GD, Ritsema M, Erkeland SJ, Bystrykh LV, Dick JE, de Haan G. Ectopic miR-125a Expression Induces Long-Term Repopulating Stem Cell Capacity in Mouse and Human Hematopoietic Progenitors. Cell Stem Cell. 2016 Sep 1;19(3):383-96. doi: 10.1016/j.stem.2016.06.008. Epub 2016 Jul 14. PMID: 27424784; PMCID: PMC5500905.
• Wright, D.J., Hall, N.A.L., Irish, N. et al. Correction to: Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes. BMC Genomics 23, 79 (2022). https://doi.org/10.1186/s12864-022-08318-w
• Mincarelli, L., Uzun, V., Wright, D. et al. Single-cell gene and isoform expression analysis reveals signatures of ageing in haematopoietic stem and progenitor cells. Commun Biol 6, 558 (2023). https://doi.org/10.1038/s42003-023-04936-6
• Wagenblast, E., Azkanaz, M., Smith, S.A. et al. Functional profiling of single CRISPR/Cas9-edited human long-term hematopoietic stem cells. Nat Commun 10, 4730 (2019). https://doi.org/10.1038/s41467-019-12726-0

Application information:

• Apply by 23.59 on Monday 25 November 2024.
• Visit the NRPDTP website for further information on eligibility, funding and how to apply: https://biodtp.norwichresearchpark.ac.uk/
• You can also visit: https://www.earlham.ac.uk/application-guidance