SCIENCE AT THE SHINE DOME canberra 6 - 8 may 2009

Early-career researchers

Thursday, 7 May 2009

RUTH STEPHENS GANI MEDAL

Dr Marnie Blewitt
Walter and Eliza Hall Institute of Medical Research

Marnie Blewitt completed her undergraduate studies in at the University of Sydney, majoring in molecular biology and genetics. She continued at the university for her honours and PhD studies, working on mammalian epigenetics – the control of gene expression. During her PhD, she designed and developed a sensitised mutagenesis screen to find novel epigenetic modifiers in the mouse, a challenging project for which she was awarded the Genetics Society of Australia DG Catcheside prize for the best PhD in genetics. Marnie moved to Melbourne in late 2005 to take up a Peter Doherty Post-doctoral Fellowship at the Walter and Eliza Hall Institute of Medical Research. There, she has worked on one of the mouse mutants identified in the mutagenesis screen, identifying a critical role for the mutated protein in X-inactivation. She has also studied the role of polycomb group proteins in hematopoietic stem cell function. Marnie is now establishing her own group within the Division of Molecular Medicine, working on the molecular mechanisms behind epigenetic control of gene expression.

Insights into molecular differences between the sexes; it is more than just genetics

Marnie’s work has focused on understanding the molecular basis for the epigenetic control of gene expression. Epigenetics is the study of reversible yet mitotically heritable changes to gene expression that do not affect the DNA sequence itself. Epigenetic marks allow the expression of restricted subsets of genes during differentiation and development, and are cleared between generations. A mutagenesis screen was used to find novel mammalian genes involved in epigenetic control and intriguing new epigenetic mechanisms, relevant to human genetics. Sex-specific effects were identified that occur prior to sexual differentiation, and so cannot be explained by hormonal differences between the sexes. In female mammals, one of the two X chromosomes is subject to epigenetic silencing, making the dose of X-linked genes equivalent between XX females and XY males. It appears that the inactive X chromosome in a female cell sequesters proteins involved in epigenetic control away from the autosomes, raising the possibility that the presence of the inactive X chromosome, rather than the absence of the Y chromosome in females, accounts for some of the differences between the sexes. One of the novel proteins identified behaves in this way, and has a critical role in the molecular mechanism of X-inactivation. The description of sex-specific effects will clearly alter the way we interpret the inheritance of phenotypic traits in humans.