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Neurogenetics and Epigenetics Research Group

Understanding the role of genes on neurodegeneration and ageing

The neurogenetics and epigenetics research group studies the relationship between genetic changes and features of dementia and related disorders. We also examine lifestyle and epigenetic factors in these diseases.

Our team examines the genetic and epigenetic influences in neurodegenerative diseases. Our research involves the study of genetic variants in specific genes that have been implicated in sporadic and heritable forms of dementia and other neurodegenerative diseases.

We work closely with other members of the ForeFront Ageing and Neurodegeneration team, using bioinformatics and next-generation sequencing to identify and investigate the role of genetic mutations in patients with neurodegenerative disorders. We focus on understanding how these mutations cause or increase the risk of disease so that we can work towards better treatment strategies.

Epigenetics involves the study of other influences on gene expression that are not caused by a change in an individual’s genetic code. These effects, however, can still have an impact on whether a gene is switched on or off and thus, are critically important for many normal cellular processes. Certain epigenetic changes have also been implicated in a variety of diseases.

Our epigenetics research is focused on examining the effects of certain lifestyle factors such as diet, exercise and other modifiable risk factors on the expression of particular genes implicated in dementia and other neurodegenerative disorders.

By better understanding the genetic and epigenetic mechanisms involved in neurodegenerative diseases, we hope to reverse the effects through preventative lifestyle changes and/or targeted treatment strategies. 

Current projects

  • A novel genetic locus for frontotemporal dementia – motor neuron disease (FTD-MND). We performed a detailed neuropathological and genetic analysis on a large European Australian family (Aus-12) with autosomal dominant inheritance of FTD and/or MND. Our project involves investigating how our dementia-causing mutation gives rise to neurodegeneration as opposed to cancer. In particular, we will create sophisticated cellular and animal models to understand how the mutant form of the protein alters fundamental biological processes.
  • Identifying epigenetic markers that are associated with exceptional longevity. Individuals living to and beyond 95 years of age are exemplars of successful, healthy ageing. We have recently shown that certain epigenetic clock models predict that the ‘biological’ age of a cohort of Sydney centenarians are younger than their chronological age. We are now trying to understand what this means in terms of the centenarians being protected against neurodegenerative diseases and whether the expression of disease genes were switched off in these individuals by epigenetic means.
  • Identifying genetic and epigenetic markers of dementia onset and progression. ForeFront has successfully collected multiple biological samples from dementia patients and ‘at risk’ individuals over a number of years. We are now examining their genes, as well as any epigenetic modifications in their blood cells, for genetic variants or differentially methylation regions, that are predictive of their disease type, onset and progression. This will have implications for earlier and more accurate diagnosis of dementia, as well as improving our understanding of the underlying biological process that leads to disease.
  • Peripheral Monitoring of Neurodegeneration using Cell-Free DNA methylation. Cell-free DNA (cfDNA) derived from brain tissue has been identified within the peripheral blood of patients diagnosed with neurological diseases, revealing the presence of unique biomarker of brain-cell death within the bloodstram. Using the distinct DNA methylation signatures of brain-cell types and brain-regions we are creating new molecular diagnostic methods using Next Generation Sequencing (NGS) that can identify brain-cell and brain-regions specific neurodegeneration through the peripheral blood in neurodegenerative patients.

Key journal publications


Associate Professor John Kwok

Forefront Neurogenetics and Epigentics Research Group