BSc (Hons); PhD
The focus of my research within the Buckle lab is the study of unexplained anaemia. Patients suffering from genetic forms of anaemia can present in childhood or adulthood and most affected individuals have lifelong moderate to severe anaemia. With secondary complications this leads to a poor quality of life, and some patients even require regular blood transfusions and have complications from iron overload.
Cultured erythroblasts are an invaluable resource for the study of erythroid disorders such as the congenital dyserythropoeitic anaemias (CDA), enabling us to determine how normal erythropoiesis occurs and at what stage things go wrong. I have shown that the cultured erythroblasts grown from haematopoietic stem cells of patients with CDA-I recapitulate this disease, with up to 40% of intermediate to late erythroblasts showing the diagnostic nuclear phenotype as seen by EM. The cells generated by this culture system are then used to characterise in detail the role of the two genes, CDAN1 and C15ORF41 that are know to be mutated in up to 70% of the cases of CDA-I. Although we have shown that late erythroblasts from CDA-I patients are abnormal it remains unclear whether the defect in these patients occurs at an earlier stage, perhaps in the stem cells or in the early erythroid progenitors. To address this question I am studying the proliferation and clonogenic potential of the patient megakaryocyte-erythroid progenitors (MEP) compared to those from normal donors. Changes in the proportions of various progenitor compartments of the blood suggests some earlier changes may be involved in the onset of CDA-I and this is a novel finding.
In 2010 I was awarded a three-year fellowship Daphne Jackson Fellowship hosted by Profs Richard Gibbons and Doug Higgs to study the role of ATRX in genome stability. After a career break this Fellowship gave me an opportunity to return to my scientific career and develop my skill set, allowing me to make the progression into my current role.
I have an on-going interest in public engagement and have been involved in numerous activities over the years in the local community and was part of the working group for the Royal Society Exhibition July 2017, with a focus on activity development.
The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin.
Truch J. et al, (2022), Nat Commun, 13
Recapitulation of erythropoiesis in congenital dyserythropoietic anaemia type I (CDA-I) identifies defects in differentiation and nucleolar abnormalities.
Scott C. et al, (2020), Haematologica, Online ahead of print
Genetic and functional insights into CDA-I prevalence and pathogenesis.
Olijnik A-A. et al, (2020), J Med Genet
An integrated platform to systematically identify causal variants and genes for polygenic human traits
Downes D. et al, (2019)
A tissue-specific self-interacting chromatin domain forms independently of enhancer-promoter interactions.
Brown JM. et al, (2018), Nat Commun, 9