Schizophrenia Research Group
Sharon Hollins, Joshua Atkins, Michael Geaghan, Ebrahim Mahmoudi, Dylan Kiltchewskij-Brown
The human brain is by far the most complex of organs, with around 100 billion neurons interconnected by up to 1000 trillion synapses.
During development, the formation, position and connectivity of these cells is precisely regulated and yet remain responsive to external sensory input and output from internal processing.
The group is interested in understanding the molecular systems that regulate neural development and synaptic plasticity so they can identify the underlying molecules and mechanisms that orchestrate the formation and behaviour of neural circuits.
These circuits provide the physiological basis of neural activity-associated logic, and their structure and plasticity is the foundation for a life-long capacity for learning and cognition.
These systems are sensitive to genetic and environmental influences, and a complex combination of these neurodevelopmental challenges can lead to neurocognitive and neuropsychiatric disorders such as schizophrenia.
By investigating the molecular neurobiology of these complex systems, and the syndromes that interfere with their normal function, the group has the potential to better understand human brain development and function.
These steps also provide a strong basis for developing biomarkers of brain disease and novel therapeutic strategies to defeat the most devastating neurocognitive disorders.
In 2015 the group made important methodological and theoretical advances that support their investigation of the complex systems biology of neurodevelopment, synaptic function and schizophrenia.
To explore the role of schizophrenia-associated miRNA in vivo the group have successfully implemented lentiviral transduction of the rat brain (collaboration with Chris Dayas and Rohan Walker) and observed schizophrenia-related neurobehavioural phenotypes.
They have also been developing a framework for high-resolution translational genomics using whole genome sequencing and applying this for personalised analysis of schizophrenia patients using integrated systems biology.
This research has made spectacular progress through the support of a NSW Health Collaborative Genomics Grant ($800,000), which enabled the group to sequence the entire genome of 500 participants in the Australian Schizophrenia Research Bank.
Further refinement in their understanding of the function of non-coding variants is being achieved through the development of isogenic cell lines produced through RNA-guided genome editing using the Cas9/CRISPR approach.
Support for this initiative was obtained from the US Brain and Behavioural Research Foundation, Independent Investigator Grant (US $100,000).