Epilepsy Functional Genomics Group
The most severe childhood epilepsies are caused by genetic variants in ion channels and synaptic proteins. Their severity is determined by the occurrence of seizures that are resistant to treatment by anti-seizure medications and are accompanied by neurodevelopmental delay, psychiatric manifestations, movement disorders and autism.
Our group specialises in modelling these epilepsy forms (also known as developmental and epileptic encephalopathies) using a variety of biological systems to investigate the disease mechanisms and test innovative therapies using state-of-the-art functional and genomic approaches.
Our group works with the Ion Channels and Human Diseases Group on several major projects including the development of induced pluripotent stem cell models and antisense therapies for neurogenetic disorders. Our projects are highly translational as we work closely with clinical teams and industrial partners.
Our group is home to researchers with expertise in various areas such as molecular biology, bioinformatics, stem cell biology, electrophysiology, and functional imaging.
Research interests
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Techniques
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About our research
We aim to model genetic epilepsies and develop novel therapies.
Our model systems include mammalian cell lines, genetic mouse models and human stem cell-derived neuronal models (2D and 3D). Molecular techniques are used to validate the specific models established while functional assays and genomic profiling can reveal the disease mechanism and test the efficacy of novel treatments.
Antisense oligonucleotides are designed in the lab based on the gene expression requirements for the gene of interest. Bioinformatics workflows are incorporated to filter the ASOs for toxicity/non-specific targets.
The ASOs are then screened in in vitro cell-based assays that are suitable for high-sensitivity read-outs. The regulation of the transcript expression is confirmed at the protein level by western blotting/mass spectrometry.
The main methods adopted include high-throughput gene expression analysis in various immortalised cell lines and in iPSC-derived neurons using qPCR and digital PCR. RNA sequencing (short and long read sequencing) is also adopted to understand transcriptome-wide gene expression changes.
Research project
Research team
Research team head
Associate Professor Snezana Maljevic
Group Head
Team members
Dr Sannu Thomas
Research Fellow
Dr Cristiana Mattei
Research Fellow
Dr Miaomiao (Cherry) Mao
Research Fellow
Dr Selvam Paramasivan
Research Fellow
Dr Jana Janaththani
Research Fellow
Dr Julia Loseff-Silver
Research Fellow
Team members
Research and technical staff
- Alicia Sedo
- Erlina Syazwan
Honours students
- Sarah Handcock
PhD students
- Montanna Waters
- Lucas Teasdale
Selected publications
- Mao M, Mattei C, Rollo B, Byars SG, Cuddy C, Berecki G, Heighway J, Pachernegg S, Menheniott T, Apted D, Jia L, Dalby K, Nemiroff A, Mullen S, Reid C, Maljevic S and Petrou S (2023), ‘Distinctive in vitro phenotypes in iPSC-derived neurons from patients with gain- and loss-of-functionSCN2Adevelopmental and epileptic encephalopathy’, bioRxiv (Cold Spring Harbor Laboratory), doi:10.1101/2023.02.14.528217
- Heighway J, Sedo A, Garg A, Eldershaw L, Perreau V, Berecki G, Reid C, Petrou S and Maljevic S (2022), ‘Sodium channel expression and transcript variation in the developing brain of human, Rhesus monkey, and mouse’, Neurobiology of Disease, 164:105622. doi:10.1016/j.nbd.2022.105622
- Burbano L, Li M, Jancovski N, Jafar-Nejad P, Richards K, Sedo A, Soriano A, Rollo B, Jia L, Gazina EV, Piltz S, Adikusuma F, Thomas PG, Kopsidas H, Rigo F, Reid CA, Maljevic S and Petrou S (2022), ‘Antisense oligonucleotide therapy for KCNT1 encephalopathy’, JCI insight, 7(23), doi:10.1172/jci.insight.146090
- Rosa F, Dhingra A, Uysal B, Mendis C, Loeffler H, Elsen GE, Mueller SG, Schwarz N, Castillo-Lizardo M, Cuddy CE, Becker F, Heutink P, Reid CA, Petrou S., Lerche H and Maljevic S (2020), ‘In vitro differentiated human stem cell-derived neurons reproduce synaptic synchronicity arising during neurodevelopment’, Stem cell reports, 15(1):22–37, doi:10.1016/j.stemcr.2020.05.015
Contact us
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