Associate Professor Murray Cairns believes tiny molecules in the brain may be the key to understanding the causes of a perplexing neuropsychiatric disorder.
The brain is the most complex of organs, with 100 billion neurons each connected to up to 100,000 other neurons. To understand how irregularity within that intricate network can lead to schizophrenia, Associate Professor Murray Cairns delves deep into the innermost workings of brain cells, studying the effect that tiny molecules called microRNA have on the function of genes.
"One of the main hypotheses around schizophrenia is that during development of the brain there is a problem with the ability of neurons to make connections with each other," Cairns explains. "My focus is on the role of microRNA in brain development, looking in particular at how they regulate gene expression – whether those genes are switched on or off and what controls that activity. The central dogma of molecular biology is that the gene makes RNA and RNA makes protein, but these microRNA can prevent that protein being produced, effectively 'silencing' – or switching off – the gene."
MicroRNA molecules play a key role in regulating genes but were not discovered by scientists until 1993 and have only been intensively studied since the early 2000s. As a postdoctoral scientist, Cairns was part of a commercial biotechnology research team at the forefront of that movement. "It was a high-powered group of researchers with cutting-edge skills in gene delivery and gene suppression technology, so it was a great training ground," recalls Cairns, who completed a PhD in molecular biologyat the University of New South Walesin 1998.
A scientific and personal interest in schizophrenia attracted him in 2005to a Schizophrenia Research Institute (SRI) fellowship at the University of Newcastle. Cairns now leads his own research team, which last year achieved a breakthrough by identifying a number of microRNA on chromosome 14 that are depleted in the blood of schizophrenia sufferers. The discovery has the potential to lead to the development of a blood biomarker for schizophrenia, which could assist in earlier diagnosis of the disorder, as well as better predictions of susceptibility and likely response to treatments. The finding of this genetic signature was published in the journal Molecular Psychiatry. Cairns and his team are now extending their research into the causes of this down-regulation and its impact on gene expression.
As well as ongoing support from the SRI and the Hunter Medical Research Institute (HMRI), Cairns has received substantial grants from the US-based National Alliance for Research on Schizophrenia and Depression (NARSAD) and the National Health and Medical Research Council (NHMRC), which awarded him $485,000 in 2010 to lead research into the molecular and cellular characterisation of schizophrenia-associated dysfunction in microRNA. Another $573,660 NHMRC grant received this year, administered through the Brain and Mind Research Institute, will allow Cairns and his collaborators to progress to a biological evaluation of microRNA involved in schizophrenia.
While scientists remain confounded by the causes of schizophrenia, a mental illness that affects one per cent of people worldwide, Cairns believes research is drawing closer to unlocking the mysteries of the disorder.
"We know schizophrenia has a large genetic component but researchers have been unable to pin it on any one gene," he states. "Also, it is a disease that doesn't have any obvious neuropathology – it doesn't produce lesions on the brain like Parkinson's or Alzheimer's disease – so it is much harder to examine scientifically.
"What does seem obvious is that it is the result of a network dysfunction – a problem in the brain's wiring – and that is what my research is investigating, right down to the very molecular level."