The main PhD work of Tianyi is now published in Nature Communications. He used biotinylation by antibody recognition (BAR) method to uncover the proximal interactome of the RNA demethylase, FTO. Importantly, Tianyi identified a role of FTO in DNA damage response, acting as a negative regulator of PARP1 independent of its role as the RNA demethylase. Thanks to all co-authors and collaborators involved in this project. 

Victor, Hilary and Lingrui attended the BioMolecular Horizon 2024 in Melbourne. Lingrui was awarded an ASBMB student bursary and Hilary received the Young Scientist Program (YSP) Fellowship.
​Victor also organised the inaugural Australian (ASBMB) and Korean Society for Biochemistry and Molecular Biology (KSBMB) Joint Meeting on Molecular Neuroscience on 21 September 2024 at the Bio21 Institute, Melbourne.  Thanks to Australia-Korea Foundation (AKF) and Clem Jones Centre for Ageing Dementia Research (CJCADR) for sponsoring this symposium. 

A collaborative study led by Adam Hines from the van Swinderen's Lab (QBI, UQ), has identified a specific effects of isoflurane anesthesia in impairing synaptic release and presynaptic protein dynamics in excitatory cholinergic synapses in the adult Drosophila brain. It has little effect on inhibitory GABAergic or glutamatergic synapses. These findings suggest a presynaptic inhibitory mechanism that complements the other inhibitory effects of anesthesia. The paper was published in Journal of Neuroscience. [The Conversation]​

​Understanding the molecular changes associated with the aged brain forms the basis for developing potential strategies for slowing cognitive decline associated with normal aging. In a new study published in Proteomics, we reported global changes in the hippocampal proteome in advanced aged (20 months) and young (3 months) male mice. Many proteins are up-regulated in microglia, astrocytes and oligodendrocytes, while most of the neuronal proteins are down-regulated. Congratulations to River and Jocelyn, who led this study with our wonderful collaborators, Dr. Mark Graham (Children's Medical Research Institute, Sydney) and Dr. Ashley van Waardenberg (iSynapse). 

We are very proud to present Dr. Tianyi Zhu, who successfully defended his PhD thesis this year. Tianyi has been working on the RNA demethylase FTO in the laboratory. We are very proud of his achievement and stay tune for Tianyi's study, which is currently in revision. 

We are thrilled to share our new study published in Cell Reports which reports the identification of a neuronal-specific cytosolic C2 domain-containing calcium-binding protein Copine-6 as a postsynaptic calcium sensor that mediates AMPA receptor exocytosis during synaptic potentiation. Congratulations to Anson and Joanne, who co-lead this study, and our wonderful collaborators Prof. Brett Collins and Dr Mintu Chandra (IMB, UQ) and members of the Anggono Lab who contributed. 

A new collaborative study led by Dr. Angelo Keramidas and his team at IMB, UQ is now published in Epilepsia, which reports the mechanisms that underlie the pathogenicity of three new GRIN1 (which encodes the GluN1 subunit of NMDA receptors) missense variants. Sooraj investigated the surface expression of these GluN1 mutants in primary hippocampal neurons. Congratulations Lotten, Angelo and all co-authors.  

We are delighted to make a small contribution in a new study led by Dr. Tara Walker (QBI, UQ) and her team, which reports the discovery of platelet factor 4 (PF4) in mediating the rejuvenating effects of exercise during physiological brain ageing. This work was published in Nature Communications. Congratulations Odette and Tara! Similar results are reported by the Villeda Lab (Nature) and the Dubal Lab (Nature Aging). 
Commentaries in Nature, Nature Cardiovascular Research, Immunity, Forbes. [Press Release]

Post-translational ubiquitination of GluA1 controls the post-endocytic sorting of AMPA receptors into the lysosomes for degradation. To investigate the functional importance of GluA1 ubiquitination in vivo, we generated and studied the GluA1 K868R knock-in mice. We report in the Journal of Neuroscience that these mice exhibit enhanced hippocampal long-term potentiation (LTP) and deficits in long-term depression (LTD). Consequently, these mice display deficits in short-term spatial memory and cognitive flexibility. Congratulations to Sumasri for her second first-author papers, as well as to the other co-first authors, Pojeong Park and Dae Hee Han. This is a wonderful collaboration with Prof. Bong-Kiun Kaang (Seoul National University, Korea). 

A new study from the team of Dr. Albert Lee (Macquarie University) reports the proximal interactome of phosphorylated Tau protein in the post-mortem brains from patients with progressive supranuclear palsy (PSP). This study, which appears in Journal of Neurochemistry, combines quantitative proteomics with biotinylation by antibody recognition (BAR) approach. Tianyi and Jocelyn from our lab contributed to this collaborative study.  

Our new research describing the m6A-epitranscriptomic profiles from the hippocampi of young (3 month-old) vs aged (20 month-old) C57Bl/6 mice is now out in Aging Cell. We reveal more over 500 transcripts that are differentially methylated. There is also a significant concordance between m6A and transcript levels in both directions. Finally, we found that the myelin regulator gene Gpr17 was downregulated in the aged hippocampus concomitant with reduced m6A levels in its 3'UTR. Overall, the positive correlation between m6A and the transcript expression levels indicates a co-transcriptional regulation of m6A with gene expression changes that occur in the aged mouse hippocampus. Congratulations to River and Jocelyn who lead the project, as well as to our fantastic collaborators Drs. Renhua Song and Justin Wong (Centenary Institute, Sydney). 

We are very proud to introduce Dr. River Huang, our lab third PhD graduate. River will soon be taking up a new position as a postdoctoral researcher at The Johns Hopkins University of School of Medicine in Baltimore, USA.  Congratulations River and we wish you all the very best!  

We are delighted to that our new work is now published in Open Biology. Here we reports the structural basis of familial ALS-associated SFPQ variants in promoting the formation of SFPQ cytoplasmic aggregates through enhanced zinc binding. We also found that these aggregates alter the expression of AMPA receptors on the plasma membrane of primary neurons, a phenotype that is commonly found in ALS patients. This is another great collaboration with the lab of Mihwa Lee (La Trobe University) and is an extension of our previous work published in Nucleic Acids Research. Well done Jocelyn, Nishita, Anson and Lara for contributing to this study. Thanks to MND Research Australia (Judy Mitchell MND Research Innovator Grant) for supporting this research. 

A collaborative study led by Dr Xue Yan Ho from the Hilliard's Lab (QBI, UQ), has identified a molecule essential for regulating the repair of injured nerves, which could help people recover from nerve damage. Xue Yan found that the metalloprotease ADM-4/ADAM17 promotes regenerative axonal fusion by stabilizing the fusogen EFF-1. The paper was published in the journal Science Advances. A great collaboration with Prof. Massimo Hilliard, Dr Sean Coakley and Dr Rumelo Amor. [Press Release]​

Jocelyn wrote an opinion piece that was published in Trends in Genetics. We propose a unifying mechanism that explains the complexity of YTHDC1 (the nuclear m6A reader) in regulating gene expression. Another great collaboration with Dr Justin Wong (Centenary Institute, Sydney). 

Happy to share our new review article by Jocelyn on the m6A regulatory mechanisms of brain plasticity, learning and memory, which has just been accepted for publication in Seminars in Cell and Developmental Biology. A great collaboration with Dr. Justin Wong (Centenary Institute, Sydney).

The lab attended the Clem Jones Centre for Ageing Dementia Research annual retreat at the beautiful Custom House. We were very pleased that our students, Hilary and River, received the best research student publication award (Yong et al., Cell Reports, 2020) and the student's lay abstract presentation people's choice award, respectively. Congratulations! 

We are very excited to share our lab very first pre-print on bioRxiv. This work, led by our PhD student Hilary Yong, identified functional roles of CaMKIIα-mediated phosphorylation on the C-terminal tail of the GluN2A subunit (Ser-1459) in regulating the gating and activity-dependent trafficking of NMDA receptors. It is an extension of our recent collaborative work that was published in Cell Reports (Vieira et al., 2020). We thank all authors and our wonderful collaborators, Prof. Brett Collins (IMB, UQ), Dr. Angelo Keramidas (IMB, UQ), Prof. Joe Lynch (QBI, UQ) and Prof. Katherine Roche (NINDS, NIH, USA). 

Even though 2020 has been a tough year, we have performed well with 7 published papers, two of which were led by PhD students, River and Hilary. To cap off the year, the lab was awarded the Judy Mitchell MND Research Innovator Grant by the MND Research Australia. This grant was jointly awarded to Victor, Jocelyn and our collaborator, Dr. Mihwa Lee (La Trobe University) to investigate molecular mechanisms underlying the cytoplasmic aggregation of the RNA binding protein, SFPQ, in ALS. Finally, we are very proud of Hilary, whose work on PICK1 in synaptic vesicle recycling (Yong et al., Cell Reports, 2020) was selected as the Runner Up of QBI Best Student Publication Prize 2020. We wish everyone a happy festive season and all the very best in 2021.  

Our latest work has just been published in Cell Reports showing a new role for PICK1 (the only protein with a BAR and a PDZ domain) in regulating the activity-dependent clustering and retrieval of presynaptic vesicle cargo in mammalian central neurons. It is required for efficient synaptic vesicle endocytosis and sustained glutamate release. Outstanding work by Hilary and a wonderful collaboration with Prof. Mike Cousin (The University of Edinburgh, UK). 

A new collaborative study led by the Roche's Lab at the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), is now published in Cell Reports. This study identified CaMKIIα phosphorylation of the GluN2A subunit on Ser-1459 as a mechanism regulating NMDA receptor trafficking. An epilepsy-associated rare variant at this same residue, GluN2A-S1459G, results in altered protein interactions, decreased NMDA receptor surface expression, and reduced synaptic function, providing potential insight into an epilepsy phenotype. Congratulations to the lead author, Dr. Marta Vieira, and Katherine on this beautiful work. 

We are excited to share our new work, "Altered expression of the m6A methyltransferase METTL3 in Alzheimer's disease", which has just been published in eNeuro. Here we report a decrease in the expression of METTL3 mRNA and soluble protein in the postmortem hippocampal tissues of Alzheimer's disease (AD) patients. We also identified a striking alteration in the METLL3 protein expression, including enhanced insolubility and immunoreactivity in the AD hippocampus. Our results suggest that perturbation of m6A signalling may present a novel cellular mechanisms underpinning dysregulation of gene expression associated with AD pathophysiology. Congratulations to River and Jocelyn who led this study and to our QBI collaborators, Drs. Judith Camats-Perna and Rodrigo Medeiros.