Our new study, led by a former PhD student Dr Rezanur Rahman, has now been published in OMICS. In collaboration with the Gratten Lab at the Mater Research Institute, Reza performed SMR (Summary-data-based Mendelian Randomisation) analysis to investigate the direct association between m6A genetic variation and the risk of Alzheimer's disease. Our current study found limited evidence for a direct association between m6A genetic variation and the risk of AD. Larger m6A-QTL datasets will be required to establish whether m6A variation is associated with the risk of AD. Congratulations Reza, and we are grateful for the expertise brought by our wonderful collaborators, Dr Yuanhao Yang and Prof. Jake Gratten. 

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. 

​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.  

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!  

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). 

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. 

We wish to congratulate the following lab members for their achievements:

• Dr. Sumasri Guntupalli - for successfully passing her doctoral thesis and completing her PhD degree. Sumasri is the lab's second PhD graduate and we are very proud of her. 
• Hilary Yong - for being awarded the prestigious Ian Lindenmayer PhD Top-Up Scholarship (up to 4 years of support). We also extend our gratitude to the Lindenmayer family for their generous gift which enabled this award. The top-up scholarship was established in 2019 and funded from a donation from Robina Lindenmayer in the name of her husband, Ian Lindenmayer.
• Dr. Jocelyn Widagdo - for being awarded a UQ Amplify Fellowship (2020 - 2022) that continues to support her research in the epitranscriptomics mechanisms underlying neuronal plasticity, as well as providing her the opportunity to engage with students through undergraduate teaching at the School of Chemistry and Molecular Biology.  

We are delighted that our study, primarily done by Jocelyn and Jun Wei, has just been published in Cellular and Molecular Neurobiology. Here, we demonstrated the cross-modulation between the ubiquitination and phosphorylation of the GluA2 subunit of AMPA receptors by protein kinase C (PKC). Interestingly, this effect is specific for GluA2 as phorbol ester does not potentiate bicuculline-induced ubiquitination of the GluA1 subunit. We envisage that the binding of glutamate on AMPARs in neurons with high level of PKC activity (such as following the activation of mGluRs) will result in subunit-specific regulation of AMPAR ubiquitination and intracellular sorting, which ultimately govern the subunit composition and number of AMPARs, including the Ca2+-permeable AMPARs at synapses. 

The N-methyl-D-aspartate glutamate receptors (NMDARs) mediate calcium-dependent signaling that underpins multiple forms of synaptic plasticity. Different GluN2 (GluN2A-D) subunit confers NMDARs with distinct ion channel properties and intracellular trafficking pathways. In a review article which has just been published in Journal of Neurochemistry, we discuss the current knowledge of the molecular mechanisms that regulate the trafficking of GluN2-containing NMDARs, focusing on the roles of several key synaptic proteins that interact via their carboxyl termini. This review article is a joint effort with our collaborator Prof. Katherine Roche (NINDS, NIH). Congratulations to Marta (Roche Lab) and Hilary (Anggono Lab) on an excellent work. 

We are excited to welcome Dr. Anson Tan (postdoctoral fellow) and Mr. Sooraj Das (PhD student), who have just joined the Anggono Lab to investigate the mechanisms of glutamate receptor trafficking in neurons. Anson received his PhD from the University of Melbourne studying the mechanisms of APP trafficking under the supervision of Prof. Paul Gleeson, while Sooraj received his BS-MS double degree from the Indian Institute of Science Education and Research (IISER) Pune, India. We are also very fortunate to retain Ms Hilary Yong (former Research Assistant), who will pursue her PhD degree in the lab. Both Sooraj and Hilary received highly competitive Research Training Program Scholarships from the Australian Government. 

We are delighted to welcome Mr. Liming Yang, a third year Bachelor of Medical Science student from the University of Exeter, UK. Liming will undertake a one-year research in the Anggono Lab as part of the Professional Training Year programme. 

A big congratulations to Joanne, who has been awarded her PhD degree and has officially became our lab's first PhD graduate. Well done!!!