Advanced imaging of the actin cytoskeleton in megakaryocyte: The role of actin in platelet formation.

This project will use these state-of-the-art advanced microscopy techniques to study the dynamic reorganisation of the actin cytoskeleton that are required for proper proplatelet formation and platelet release.
Blood platelets are generated from their progenitor cell, the megakaryocyte, in the bone marrow by a complex process known as Proplatelet Formation (PPF). This process is dependent on dynamic reorganisation of the megakaryocyte cytoskeleton and a complex membranous system within the megakaryocyte. Understanding how these factors contribute to the mechanisms of PPF will enable us to understand the underlying basis of diseases that affect platelet formation and function.
Recently, several advanced imaging techniques have been developed that allow visualisation of the cytoskeleton with high spatial and temporal resolution in 3D. These include STORM super-resolution microscopy, correlative light-electron microscopy (CLEM) and lattice light-sheet fluorescence microscopy (LLS). We have extensive experience in STORM (Birmingham) and CLEM (Leicester) and the Birmingham group is the first in the UK to acquire the Lattice light sheet system. Our group is applying these technique to the study of platelets and megakaryocytes.
The project will primarily be based in Birmingham with close collaboration and interaction with Professor Mahaut-Smith in Leicester. Both labs have international reputations in the megakaryocyte field and the student would be provided training in the culture of megakaryocytes and in the imaging techniques to be used.