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Triple Marsden success for DSM researchers

Tuesday 8 November 2016 12:15pm

The Dunedin School of Medicine warmly congratulates Professor Stephen Robertson from the Department of Women's and Children's Health, and Professor Mike Eccles and Associate Professor Julia Horsfield from the Department of Pathology who have achieved a collective $2.5 million in Marsden funding.

Associate Professor Julia Horsfield gained $810,000 for her project: Becoming master of your destiny: insights into genome activation from nuclear structure.

Associate Professor Julia Horsfield and co-principal investigator Dr Justin O'Sullivan are collaborating to gain new insights into the very beginnings of life, by using cutting edge genomic techniques to study how a zygote - the cell that forms from the union of sperm and egg – activates its newly minted genome and becomes the master of its own genetic destiny.Julia says that when a zygote forms, its brand new genome is kept mostly inactive at first.
“However, at a defined time-point, the zygotic genome becomes active and is transcribed – its genes are switched on. At this crucial time, the embryo becomes master of its own destiny," says Assoc Prof Horsfield.
Testing their theory that a special 3D structure forms in the cell’s nucleus and permits transcription to occur and triggers genome activation, Dr O’Sullivan says the team will use sophisticated genomics techniques that can probe nuclear structures in zebrafish embryos. The researchers will also use live imaging of zebrafish embryos and individual cells as they undergo genome activation to look at visible changes in the nucleus as genes are switched on.
“As well as aiming to discover the nuclear structure that triggers genome activation, we hope to disrupt the structure to determine how important it is for gene activation. Establishing how the zygotic genome is at first held inactive, and how it rapidly becomes activated, will provide new insight into the earliest stages of life, he says.
Associate Professor Horsfield says she is delighted by the $810,000 in Marsden funding, which will also enable a new collaboration with the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany.
“It will bring our far-flung team together to tackle one of the biggest enigmas in biology – how an individual expresses its genetic identity for the first time."

Professor Stephen Robertson received $825,000 for Bones under pressure. How does the skeleton sense gravity?

Scientists understand that repetitive stress on bone leads to increased strength and higher bone density, whereas disuse can cause them to thin - an effect much like that in our muscles. This suggests the existence of a "bone bio-sensor" that registers mechanical stress and activates an appropriate response.

Professor Stephen Robertson and Dr Sujay Ithychanda from the US-based Lerner Research Institute, have discovered mutations in two different human genes that result in excessive bone density, or hyperostosis, where bones are denser and stronger than normal. Their project will investigate whether the proteins encoded by these genes represent the long-sought sensor of mechanical stress in bone-forming cells.

Finding out how our bones sense mechanical stress - and how this leads to increased bone density and strength - could lead to new therapies being developed for treating bone loss in osteoporosis or during immobilisation of fractures. This project will also study how our bones sense environmental signals.

How our skeleton interacts with gravity may even shed light on ways to combat the effects of weightlessness on bones during space travel.

Professor Mike Eccles received $825,000 for The genes of life and death: a role for placental-specific genes in cancer?

Invasive cancers are hard to treat. If we determine how cancer cells become invasive, then we will discover new strategies for early diagnosis or treatment. Good models for cancer invasion in humans are rare, but remarkably, the human placenta could be an excellent model for cancer because of its invasive features.

The placenta invades the adjacent uterus, like cancer erodes into surrounding organs. It also takes hold of the immune system to prevent rejection of the fetus, just like cancer controls the local immune response. Intriguingly, placental and cancer cells share a genetic phenomenon that we do not understand - they fail to silence virus derived DNA sequences, known as retrotransposons, that are normally silenced in healthy tissues. Retrotransposon unsilencing is usually associated with gene disruption, sometimes causing cancer. However, in the placenta, retrotransposon unsilencing creates new genes that are essential for placental function.

Mike Eccles and his team have evidence that these placental genes are activated in cancer, and believe retrotransposons may offer powerful perspectives on cancer prevention and treatment. By using the placenta as a model for malignancy, they aim to determine the implications of retrotransposon activity in cancer and expect to identify new genes that control cancer invasion.