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PIN1ng down heterochromatin to prevent cellular ageing

24 months
Approved budget:
Dr Tracy Hale
Dr Helen Fitzsimons
Professor Martin Williams
Health issue:
Proposal type:
Explorer Grant
Lay summary
For all of us, ageing is inevitable and inescapable, and with our ageing population, New Zealanders are particularly vulnerable to ageing-related diseases. At the cellular level, ageing is associated with reduced integrity of the nuclear envelope, however the mechanisms through which this contributes to cellular ageing remain elusive. The three-dimensional nucleus is defined by the nuclear envelope, within which DNA is packaged into chromatin. Despite this, the structural role that chromatin plays in nuclear integrity has been largely ignored. We have shown that HP1α, an architectural protein that compacts chromatin, is essential for maintaining chromatin integrity at the nuclear envelope. By employing a multidisciplinary approach, we will identify the factors that regulate HP1α-dependent tethering and determine the mechanisms through which HP1α protects nuclear integrity. We will propose a new molecular model of nuclear envelope function; a model that will transform knowledge in areas such as neurobiology and regenerative medicine.