Research Members

Expertise: m6A RNA methylation, RNA binding proteins, CRISPR editing, post-translational modifications, synaptic neurobiolog. RBPs, RNA mods and lncRNA in plasticity, aging and stress

The Anggono lab's current research aims to elucidate the molecular mechanisms by which m6A (N6-methyladenosine) and related RNA binding proteins regulate activity-dependent gene expression during neuronal plasticity, and how aberrant dysregulation of the m6A signalling contributes to the pathophysiology of neurodegenerative diseases, such as Alzheimer’s and motor neuron disease.

RNA biology of neuronal plasticity

Synaptic plasticity and long-term memory require de novo gene transcription and new protein synthesis. It is now well established that these two fundamental cellular processes are tightly regulated at the level of RNA (by non-coding RNAs, RNA modifications and RNA binding proteins). We provided the first evidence for a role of the long non-coding RNA, Meg3, in regulating the trafficking of AMPA-type glutamate receptors during neuronal plasticity (Tan and Widagdo et al., Frontiers in Cellular Neuroscience, 2017). One of the current goals of the laboratory is to elucidate the roles of post-transcriptional methylation of RNA on adenosine at the N6-position (termed m6A) in the healthy and disease brain (Widagdo and Anggono, Journal of Neurochemistry, 2018; Widagdo et al., Semin. Cell Dev. Biol., 2022). In collaboration with A/Prof. Tim Bredy (QBI, UQ), we were first to demonstrate the role of m6A RNA methylation in memory consolidation (Widagdo et al., Journal of Neuroscience, 2016). Subsequently, we identified a striking alteration in the expression of the m6A methyltransferase METLL3 in the postmortem human AD (Alzheimer’s disease) brain (Huang et al., eNeuro, 2020), suggesting that perturbation of m6A signalling may underpin dysregulation of gene expression associated with AD pathophysiology, and potentially other neurodegenerative diseases.

Our research in this field has also been extended to understanding the structure and function of RNA binding proteins. We identified an essential role of ubiquitin signalling in regulating the proteasomal degradation and nuclear translocation of the RNA demethylase, FTO (Zhu et al., Journal of Molecular Biology, 2018). More recently, work in collaboration with Dr. Mihwa Lee (La Trobe University) has identified a structural and molecular basis of the zinc-induced cytoplasmic aggregation of the RNA binding protein SFPQ (Huang et al., Nucleic Acids Research, 2020). This study provides a novel conceptual framework on how metal-induced polymerisation of RNA binding protein mediates cytoplasmic aggregation, a form of protein misregulation that is commonly associated with neurodegenerative diseases, including AD and MND (motor neuron disease or amyotrophic lateral sclerosis).

Expertise: RBPs in development

Malformations of the neocortex arising from the inability to replenish the stem cell pool or undergo neurogenesis during embryonic life has profound consequences for an individual’s survival and quality of life. Moreover, perturbation of these critical developmental processes is directly implicated in autism spectrum disorders (ASDs). The Fragile X syndrome protein, FMRP, binds mRNAs to inhibit translation by forming a complex with Cyfip1 and the translation initiation factor EIF4E. The Cooper lab has identified a regulatory mechanism involving ASD genes that spatiotemporally controls Cyfip1 activity in neural stem cells in the developing mouse neocortex (Lee et al, Nature Comms 7:11082, 2016; O'Leary C, et al, Cell Rep 20: 370-383, 2017; Veeraval et al, Front Cell Dev Biol 8:6, 2020). Using gene editing and in utero electroporation approaches, they have developed mouse models to investigate the consequences of disrupting Cyfip function in cortical neural stem cells and in human induced pluripotent stem cells. Activity-induced mRNA translation within dendritic spines is essential for synaptic plasticity. The Cyfip-FMRP complex also negatively regulates the translation of many critical mRNAs in the spine, including NMDA and group 1 metabotropic glutamate receptors (NMDARs, mGluRs) and the morphogenic factor BDNF relieves translational repression by triggering Cyfip1 dissociation from FMRP-EIF4E. Using biochemical and calcium imaging techniques as well as super-resolution microscopy, the Cooper lab has recently demonstrated that their ASD gene regulatory pathway modulates Cyfip1-FMRP interactions during spine morphogenesis in response to BDNF-mediated synaptic stimulation, suggesting a pivatol role in synapse formation and transmission (manuscript in preparation).

1. Dr Xiaoying Cui has shown the long non-coding RNA (lncRNA) HOX-antisense intergenic RNA myeloid 1 (HOTAIRM1), is involved in the development of dopaminergic (DA) neurons. When interfering (si)RNA against HOTARIM1 are electroporated into the ventral midbrain of E11 mouse embryos, important factors in DA neuron specification are reduced while non-DA neurons appeared to be spared. Cellular systems appear to indicate EZH2, a histone methyltransferase may be involved.
2. We have shown in humans that the developmental vitamin D-deficiency (DVD-deficiency) increases the risk of schizophrenia and impairs various aspects of brain development particularly that of DA neurons in animals. Dr Renata Pertile has recently sequenced the microRNA (miR) molecules in embryonic DA neurons sorted from E14 DVD-deficient mesencephalon. miRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally. We have functionally analysed a number of dysregulated candidate miRs and show upregulation of miR-181c-5p suppresses neurite outgrowth of dopaminergic neurons.
3. The EDiPS animal model (Enhanced Dopamine in Prodromal Schizophrenia) recapitulates the selective progressive increase in DA synthesis in the dorsal striatum that occurs in patients who transition to disease. RNA methylation, a post-transcriptional modulation, may be relevant in dopamine-mediated behaviours. When methylated RNA(m6A) immunoprecipitation (meRIP) sequencing was conducted on dorsal striatum from EDiPs animals Xiaoying Cui showed increased m6A RNA methylation in the EDiPs dorsal striatum. Consistent with this, there was increased expression of Mettl14 writer protein and the m6A reader YTHDF1 mRNA.

Expertise: Retrotransposons, pseudogenes

Professor Geoffrey Faulkner's team has led efforts to characterise the transcriptome of retrotransposons (repetitive elements) found in mammalian genomes. Through collaboration with the FANTOM (Functional Annotation of the Mammalian Genome) consortium, Prof Faulkner generated the first large scale survey of promoter elements and transcription start sites resident in retrotransposons (Faulkner et al., Nature Genetics, 2009). Notably, these promoters were remarkably tissue-specific in their expression and, in many cases, provided alternative transcription initiation for protein-coding genes. Prof Faulkner's team are currently focused on applying long-read sequencing (PacBio and ONT) to mammalian tissues as a way to catalogue new retrotransposon-derived RNAs; these efforts have also yielded a greatly expanded repertoire of transcribed pseudogenes (Troskie et al., Genome Biology, 2021). Prof Faulkner has authored numerous reviews on the transcriptome of repetitive elements (e.g. Mattick, Taft & Faulkner, Trends in Genetics, 2010; Jansz & Faulkner, Genome Biology, 2021).

Professor Frédéric Meunier leads the Single Molecule Neuroscience Laboratory at the Queensland Brain Institute and is affiliated with the Clem Jones Centre for Ageing and Dementia Research. His research aims to define how brain cells communicate and survive in health and disease by resolving, at nanometre scale, the molecular choreography of neuronal transport and synaptic function. Using cutting-edge super-resolution and single-molecule approaches, his team dissects how proteins of the exocytic machinery are dynamically organised at the nanoscale level to underpin neurotransmitter release. A major strength of the Meunier lab is connecting fundamental nanoscale mechanisms to disease. This includes work linking mutations in Munc18 to severe epileptic encephalopathies and uncovering mechanistic connections between vesicle-fusion machinery and α-synuclein aggregation, bridging pathways implicated in epilepsy and synucleinopathies. In parallel, the lab has helped unravelled how condensate-like organisations involving Tau control synaptic vesicle organisation, with implications for disorders such as Alzheimer’s disease.

Within the Centre’s RNA in Neuroscience program, Prof Meunier brings a uniquely powerful “molecules-in-motion” toolkit to understand how RNA dynamic organisation in neurons, in the hope to better understand how are involved to synaptic function. His work has contributed to discoveries showing that synapse-enriched long noncoding RNAs can regulate the trafficking and clustering of RNA granules in an activity-dependent manner and influence fear-related learning processes. More recently, a 2025 preprint reports that neuronal Vault particles, large ribonucleoprotein complexes, carry coding and noncoding RNA cargo, and that the Vault-associated ncRNA Vaultrc5 is synapse-enriched and required for activity-dependent Vault trafficking, with synaptic knockdown shifting RNA cargo and impairing fear learning. 

Expertise: microRNA

The Zuryn lab is part of the QBI at the University of Queensland and is interested in mitochondrial genome function and dysfunction and how this relates to disease. RNA-based mechanisms likely play an intimate role in the communication between the mitochondrial and nuclear genomes, which must function together to coordinate the assembly of oxidative phosphorylation protein complexes with nanoscale precision.We have recently developed techniques in the C. elegans model system for studying the cell-specific activities of microRNAs, a family of small RNA molecules with post-transcriptional gene regulation properties. Using this system, we have uncovered microRNAs that are activated upon mitochondrial stress signals and that function to protect cells from severe mitochondrial genome damage. The functional properties of these microRNAs show promise in protecting neurons against neurodegenerative diseases associated with mitochondrial dysfunction. The Zuryn lab is also interested in mitochondrial RNA modifications and how these control mitochondrial function.