Projects per year
Personal profile
Research interests
Red blood cell development in health and disease.
In the bone marrow, red blood cells (RBC) are constantly being produced from hematopoietic stem cells (also called progenitor cells), a process called erythropoiesis. The peripheral blood of an individual also contains a host of progenitor cells that can be induced to undergo erythropoiesis. We are developing culture techniques to maximize the production of red blood cells from peripheral blood for the study of erythropoiesis. This involves exploration of the use of synthetic scaffolds environments for blood production and also interactions with stromal cells. The eventual aim being to manufacture enough RBC for transfusion purposes or novel therapeutics.
During the process of erythropoiesis, red blood cell progenitors undergo a remarkable transformation; they become smaller, express a variety of erythroid specific proteins (e.g. Haemoglobin and band 3 (AE1)), lose their nucleus and remodel their membrane to generate the nascent reticulocyte and then go on to mature further to the recognizable biconcave red blood cell. Whilst undergoing these substantial morphological changes the progenitor cell must assemble and selectively retain key membrane protein complexes (e.g. band 3 (AE1) and Rhesus proteins). These membrane protein complexes give the RBC membrane its unique antigenic and structural properties and facilitate efficient gas exchange. Very little is known about how multiprotein complexes are assembled or correctly localized during erythropoiesis or why specific alterations in membrane protein composition occur in red cell diseases such as Hereditary Spherocytosis. This is another area of focus for the lab.
The lab uses biochemical and cell biology techniques to monitor the expression and interactions of erythroid specific proteins throughout differentiation in health and disease. We are also manipulating RBC progenitor protein expression. This work will greatly enhance our knowledge of the structure-function relationships within the RBC membrane and will identify the stages and mechanisms whereby membrane protein composition is altered during normal differentiation process and during human disease. This also helps us to form a benchmark of normal erythropoiesis to explore the viability of blood cells produced using embryonic stem cells, immortalised cells or human induced pluripotent stem cells. The lab is also a member of the BrisSynBio Centre, and here we aim to use our ability to culture RBCs and manipulate them to develop the RBC as a synthetic biology chassis for novel functionality or a vehicle for novel therapeutics.
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Collaborations and top research areas from the last five years
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Immunoengineering Body Fat: Modelling microphages in a 3D-bioprinted human adipose tissue model
1/01/23 → 30/06/24
Project: Research
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Engineering inducible anhydrides for irreversible Red Blood Cell decoration
1/04/22 → 31/03/25
Project: Research, Parent
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Engineering inducible anhydrides for irreversible Red Blood Cell decoration
1/04/22 → 31/03/25
Project: Research
Research output
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Evaluation and deployment of isotype-specific salivary antibody assays for detecting previous SARS-CoV-2 infection in children and adults
Thomas, A., Oliver, E. H., Baum, H. E., Gupta, K., Shelley, K. L., Long, A. E., Jones, H. E., Smith, J., Hitchings, B. E., Di Bartolo, N. D., Vasileiou, K., Rabi, F. A., Alamir, H. I. A., Eghleilib, M. A., Francis, O., Oliver, J. L., Morales-Aza, B., Obst, U., Shattock, D. J., Barr, R. S., & 21 others , 15 Mar 2023, In: Communications Medicine. 3, 1, 14 p., 37.Research output: Contribution to journal › Article (Academic Journal) › peer-review
Open Access -
Missense mutations in PIEZO1, which encodes the Piezo1 mechanosensor protein, define Er red blood cell antigens
Karamatic Crew, V., Tilley, L. A., Satchwell, T., Alsubhi, S. A. O., Toye, A. M. & Thornton, N. M., 23 Jan 2023, In: Blood. 141, 2, p. 135-146 12 p.Research output: Contribution to journal › Article (Academic Journal) › peer-review
Open AccessFile5 Citations (Scopus)69 Downloads (Pure) -
Neutrophils cultured ex vivo from CD34+ stem cells are immature and genetically tractable
Naveh, C. A., Fleming, K. M., Toye, A. M. & Amulic, B., 14 Jul 2023, (medRxiv).Research output: Working paper › Preprint
Datasets
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Whole cell and surface protein expression assessment in macrophage subtypes
Toye, A. M. (Creator), Oates, T. C. L. (Creator) & Severn, C. (Creator), University of Bristol, 21 Apr 2023
DOI: 10.5523/bris.220i0rql3u6929ay07x99u95e, http://data.bris.ac.uk/data/dataset/220i0rql3u6929ay07x99u95e
Dataset
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Development and evaluation of low-volume tests to detect and characterize antibodies to SARS-CoV-2
Oliver, J. (Creator), Oliver, E. (Creator), Thomas, A. (Creator), Halliday, A. (Creator), Goenka, A. (Creator), Baum, H. (Creator), Gillespie, K. M. (Creator), Long, A. E. (Creator), Toye, A. M. (Creator) & Finn, A. H. R. (Creator), University of Bristol, 28 Sept 2022
DOI: 10.5523/bris.3bo7kz80s21fy2oknckvi8xq18, http://data.bris.ac.uk/data/dataset/3bo7kz80s21fy2oknckvi8xq18
Dataset
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Whole cell and surface protein expression assessment in macrophage subtype
Toye, A. M. (Creator), Severn, C. (Creator) & Oates, T. C. L. (Creator), University of Bristol, 22 Jun 2022
DOI: 10.5523/bris.2d4m29jbudzg92jg0k7gkjw23g, http://data.bris.ac.uk/data/dataset/2d4m29jbudzg92jg0k7gkjw23g
Dataset