|Dr Fiona Brown is Research Fellow|
in A/Prof Andrew Wei's lab
Researchers at the Australian Centre for Blood Diseases (ACBD) have furthered their work into Dynamin 2 (DNM2) in a paper providing the first evidence that the gene plays a role in developing red blood cells. The finding paves the way for further research investigating links to anaemia.
Mutations in Dnm2 are highly disease-specific and have been implicated in centronuclear myopathy, Charcot-Marie Tooth neuropathy and, more recently, T-cell leukaemia and Hereditary Spastic Paraplegia, but red blood cell abnormalities have not been reported to date.
Research Fellow Dr Fiona Brown said the study was made possible by a mouse model she identified in 2012, which was used in a concurrent study by the scientists that demonstrated for the first time that mutations in the DNM2 gene made leukaemia cells more aggressive.
The mouse model was identified in a genetic screen, initiated in collaboration with the Walter and Eliza Hall Institute. The screen induced random mutations in DNA, meaning the scientists did not know which genes had been mutated. Then they then screened the animals for the symptoms of anaemia.
“We went back and found the genetic mutation using gene sequencing, interrogating the DNA to find mismatches that were attributable to the disease we were seeing,” Dr Brown said. “We identified a mutation in dynamin 2.
“Dynamin 2 had previously not been implicated in the development of red cells or in anaemia so that was all extremely novel,” she said.
“The role of Dynamin 2 in cycling iron – or transporting iron into cells – was implicated but it had never been formally validated so that’s what we were able to do.” Iron, which is not produced by the body itself, is required for the formation of red blood cells.
“At the end of the report we weren’t able to establish exactly what the mutation was doing; we knew it caused anaemia but we didn’t know the process behind this.”
The study was published recently in the British Journal of Haematology. Professors Stephen Jane and David Curtis were principal investigators, while Professor Ben Kile developed the screen.
Dr Brown, who was doing her PhD at the Central Clinical School at the time, went to New York to conduct post-doctoral research at the Memorial Sloan Kettering Cancer Center. She returned two months ago to take up a position at Research Fellow in Dr Andrew Wei’s laboratory.
Brown FC, Collett M, Tremblay CS, Rank G, De Camilli P, Booth CJ, Bitoun M, Robinson PJ, Kile BT, Jane SM, Curtis DJ. Loss of Dynamin 2 GTPase function results in microcytic anaemia. Br J Haematol. 2017 Aug;178(4):616-628. doi: 10.1111/bjh.14709. Epub 2017 May 3.
Tremblay CS, Brown FC, Collett M, Saw J, Chiu SK, Sonderegger SE, Lucas SE, Alserihi R, Chau N, Toribio ML, McCormack MP, Chircop M, Robinson PJ, Jane SM, Curtis DJ. Loss-of-function mutations of Dynamin 2 promote T-ALL by enhancing IL-7 signalling. Leukemia. 2016 Oct;30(10):1993-2001. doi: 10.1038/leu.2016.100.