From Evolutionary Innovation to Precision Psychiatry: Human-Specific Small RNAs and Systems Biology Approaches for Schizophrenia

Speaker: Dr Alexandre Cristino
Senior Lecturer in Bioinformatics
Institute for Biomedicine and Glycomics
Griffith University

From Evolutionary Innovation to Precision Psychiatry: Human-Specific Small RNAs and Systems Biology Approaches for Schizophrenia

Abstract:
Schizophrenia is a highly polygenic neuropsychiatric disorder in which genetic risk is distributed across hundreds of loci, most of which reside within non-coding regulatory regions of the genome. Understanding how these variants influence gene regulatory networks and cellular function remains a major challenge for the development of effective therapies.

In this seminar, I will present two complementary research programs that address schizophrenia across distinct biological scales. First, we investigate the evolutionary origins of miR-2682, a schizophrenia-associated microRNA located within the miR-137/2682 locus, one of the strongest genetic risk regions for the disorder. By integrating structural modelling, molecular biology, and functional cellular assays, we demonstrate that human-specific sequence changes transformed an ancestral promoter-associated small RNA into a canonical Dicer1 substrate. This evolutionary innovation enables efficient miRNA biogenesis and alters neurodevelopmental phenotypes, including neurite extension and branching, providing evidence that recently evolved regulatory RNAs may contribute to both human-specific brain traits and vulnerability to psychiatric disease.

Second, I will describe an MRFF-funded precision medicine platform that uses patient-derived olfactory neural stem cells (ONS cells) as an accessible model of schizophrenia biology. By combining whole-genome sequencing, transcriptomics, proteomics, quantitative high-content imaging, and integrative systems biology, we map disease-associated molecular networks onto measurable cellular phenotypes and therapeutic responses. These approaches enable the prioritisation of candidate therapies capable of reversing patient-specific molecular signatures and cellular dysfunction. We are also exploring small RNA-based interventions as a novel strategy for directly modulating dysregulated gene networks.

Together, these studies illustrate a systems-level framework linking human evolution, gene regulation, cellular dysfunction, and therapeutic discovery in schizophrenia. By integrating multi-omics, computational modelling, and patient-derived cellular systems, we aim to advance precision medicine approaches for complex neuropsychiatric disorders.

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From Evolutionary Innovation to Precision Psychiatry
This seminar explores how human-specific regulatory RNAs contribute to schizophrenia risk and how patient-derived cellular models can be leveraged to identify personalised therapies. Combining evolutionary genomics, multi-omics, high-content imaging, and systems biology, we investigate disease mechanisms from gene regulation to cellular phenotypes while developing RNA-based and pharmacological precision medicine strategies for schizophrenia.
 

Speaker bio:
Dr Alexandre S. Cristino is a Senior Lecturer in Bioinformatics at Griffith University and leads the Neurogenomics and Systems Biology Laboratory within the Institute for Biomedicine and Glycomics. His research integrates functional genomics, systems biology, multi-omics, and computational modelling to understand how genetic variation shapes cellular function in neurological and psychiatric disorders.

Using patient-derived stem cell models, high-content imaging, and integrative bioinformatics, Dr Cristino's team investigates the gene regulatory networks underlying schizophrenia, Alzheimer's disease, and other complex brain disorders. Their work spans fundamental discoveries in human-specific regulatory RNAs and brain evolution through to the development of precision medicine approaches that connect molecular signatures with therapeutic response.

Dr Cristino has published in leading journals including Nature, Science, Molecular Psychiatry, Nature Communications, and Blood, and has secured more than $9 million in competitive research funding from the NHMRC, MRFF, and ARC. Current research focuses on identifying biomarkers and developing novel therapeutic strategies, including RNA-based interventions, for neuropsychiatric disorders.