- Buckle Group: Nuclear Organisation and Erythropoiesis Research Group
Following the completion of my Master of Science at the Otago School of Medicine in New Zealand I moved to Australia to investigate the role of BRCA1/2 splicing aberrations in breast cancer development. This work was part of three international consortia, ENIGMA (Evidence Based Network of Germline Mutant Alleles), CIMBA (Consortium of Modifiers of BRCA1 and BRCA2) and BCAC (Breast Cancer Association Consortium) which include core working groups at the Universities of Otago, Queensland, Oxford, Cambridge and Utah. I performed in vitro assays in a high throughput pipeline to quantify the level of aberrant splicing associated with BRCA1/2 variants. This work fed into a multifactorial algorithm that provides clinicians with a means of prioritising variants of unknown pathogenicity.
In January 2015 I came to the University of Oxford to work as a Research Assistant at the Molecular Haematology Unit in the laboratory of Professor Veronica Buckle. My project investigates the pathogenic mechanism of an orphan disease called Congenital Dyserythropoetic Anaemia Type-I. This disorder ranges vastly in severity from perinatal lethality to adults who are relatively healthy, yet all mutations in either of the two causative genes give rise to the same abnormal chromatin compaction in erythroblasts. To date, no clinical genotype-phenotype correlation has been established.
I have modified induced pluripotent stem cells, mouse embryonic stem cells and immortalised human erythroid progenitors using CRISPR/Cas9 to generate model systems for investigating the role of these genes, C15ORF41 (encoding C15ORF41) and CDAN1 (encoding Codanin-1), in erythropoiesis. We are currently using these systems to complement data from patient CD34+ cells and over the next few years hope to better understand the roles of C15ORF41 and Codanin-1 in red blood cell development.