Decoding blood formation: Exploring the Hidden Pathways from Stem Cells to Platelets

Background:
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[1].

Aims:
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[2], single-cell RNA sequencing, lineage tracing[1], synthetic biology, and bioinformatic[3,4] techniques established in the Wojtowicz and Haerty groups.
1. What are the molecular processes underlying stem cell high platelet production? The student will identify genes important for high platelet production.
2. The impact of which tissue of origin on platelet function.
3. Genetic validation of candidate genes identified in objective 1 using the CRISPR-Cas9 system[5].

Supervisory team, collaborations and the environment:
The student will be primarily based in the Wojtowicz group, but will collaborate closely with the Haerty and Beraza groups. This will give them 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.

References

1. doi:10.1186/s13059-023-02976-z

2.doi:10.1016/j.stem.2016.06.008

3.doi:10.1186/s12864-021-08261-2

4.doi:10.1038/s42003-023-04936-6

5.https://www.nature.com/articles/s41467-019-12726-0