Hematopoietic specification using single-cell in vivo CRISPR screen

Are you passionate about revolutionary research in stem cell biology, gene regulation, and cutting-edge molecular techniques? Join our innovative project, Hematopoietic Specification Using Single-Cell In Vivo CRISPR Screen, where you will delve into the genetic blueprint of blood formation and make impactful discoveries with real-world applications.

We have an exciting PhD opportunity investigating the genetic code of blood formation using cutting-edge CRISPR technologies. Blood is life’s vital fluid, continuously replenishing itself through a complex process known as hematopoiesis. This intricate process is orchestrated by a rare population of cells called hematopoietic stem cells (HSCs), responsible for producing all blood cells. Despite advances, the precise gene regulatory mechanisms guiding HSC formation during embryonic development remain elusive. Understanding these mechanisms is critical for advancing treatments for blood disorders, cancers, and generating blood sources in vitro.

In this project, you will employ state-of-the-art single-cell CRISPR screening techniques during chick embryo development to identify novel genes and pathways involved in the formation of HSCs. The project is joint between groups of Gi Fay Mok and David Monk at UEA and Iain Macaulay and Wilfried Haerty at EI. You will design a custom guide RNA (gRNA) library, perform in vivo microinjections, and use advanced bioinformatics to analyse gene regulatory networks. You will gain expertise in molecular biology, high-throughput sequencing, and computational biology, equipping you with a versatile skill set highly sought after in both academia and industry.

The discoveries you make could lead to new therapeutic strategies for blood disorders, improved stem cell therapies, and enhance our understanding of genetic regulation in development. By joining this project, you will be at the forefront of a field with vast translational potential, contributing to breakthroughs that could change the future of medicine.

Contact Dr Gi Fay Mok (g.mok@uea.ac.uk) for more information and discussions about the project.

References

Single cell RNA-sequencing and RNA-tomography of the avian embryo extending body axis. Mok GF, Turner S, Smith EL, Mincarelli L, Lister A, Lipscombe J, Uzun V, Haerty W, Macaulay IC, Münsterberg AE. Front Cell Dev Biol. 2024 May 28;12:1382960. doi: 10.3389/fcell.2024.1382960. eCollection 2024. PMID: 38863942

A transcriptional and regulatory map of mouse somite maturation. Ibarra-Soria X, Thierion E, Mok GF, Münsterberg AE, Odom DT, Marioni JC. Dev Cell. 2023 Oct 9;58(19):1983-1995.e7. doi: 10.1016/j.devcel.2023.07.003. Epub 2023 Jul 26. PMID: 37499658

Characterising open chromatin in chick embryos identifies cis-regulatory elements important for paraxial mesoderm formation and axis extension. Mok GF, Folkes L, Weldon SA, Maniou E, Martinez-Heredia V, Godden AM, Williams RM, Sauka-Spengler T, Wheeler GN, Moxon S, Münsterberg AE. Nat Commun. 2021 Feb 19;12(1):1157. doi: 10.1038/s41467-021-21426-7. PMID: 33608545

4D Live Imaging and Analysis of Chick Embryo Somites. Mok GF, McColl J, Münsterberg A. Methods Mol Biol. 2021;2179:173-181. doi: 10.1007/978-1-0716-0779-4_15. PMID: 32939721