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The generation of RBCs in vitro from stem cell sources and the molecular regulation of erythropoiesis in health and disease

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description

Development of systems for the generation of red blood cells (RBCs) from stem cell sources (adult peripheral blood, cord blood and pluripotent stem cells) in vitro is of great interest to health services globally, as such a product could overcome many of the problems associated with donor blood, in particular the availability of certain rare blood groups and for patients requiring repeat transfusions.

Pluripotent stem cells (PSCs) have advantages for such systems as they have the potential to provide an inexhaustible source of progenitors for the generation of large numbers of RBCs, however further research is required before mature RBCs can be generated from these cells. We are utilising innovative proteomic approaches to analyse the differential proteome, phosphoproteome and transcription factor profile of erythroblasts from such stem cells as they progress down the erythroid pathway to determine why these cells have terminal differentiation defects, followed by with genetic manipulation of identified targets to rectify.

An alternative and highly desirable approach to generate sustainable quantities of RBCs is to create immortalized adult erythroid cell lines. We have created the first such cell lines, which are undergoing extensive analysis using genomic, transcriptomic and proteomic approaches with the aim of making lines suitable for therapeutics. However, such lines have significant additional potential, for example we are using CRISPR-Cas9 genome editing to create designer lines with selected blood group phenotypes. We are also using our methodology and gene editing to create lines as disease model systems to study the underlying molecular defects of conditions such as beta thalassemia and sickle cell disease, along with the application of these lines as novel drug screening platforms.

We are also interested in the regulation of erythropoiesis, in particular transcription factors such as KLF1. KLF1 is essential for erythropoiesis and mutations in this transcription factor can result in severe red blood cell disorders. We are investigating how such mutations cause disease using genomic, transcriptomic, proteomic and biochemical approaches to determine the underlying molecular mechanisms.

We are part of the NIHR Blood and Transplant Research Unit (BTRU) to advance research on the manufacture of red blood cells from stem cells and their translation from the lab to human trials, along with researchers at NHS Blood and Transplant (NHSBT, Bristol) and Dr Ash Toye within the University.

Related Subjects

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