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 resistant to treatment by anti-seizure medications and accompanied by neurodevelopmental delay, psychiatric manifestations, movement disorders and autism. Our group specializes 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.
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 immortalized 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.
- Genetic epilepsy
- Developmental and epileptic encephalopathy (early childhood genetic epilepsy syndrome)
- Induced pluripotent stem cell-derived neuronal models.
- Functional analyses of cellular activity in a range of biological systems
- RNA-targeted therapeutics
- Generation of iPSC-derived neuronal models (monolayer cultures and brain organoids)
- Patch clamp, two-microelectrode voltage clamp
- 2-photon calcium imaging
- High throughput in vitro cell screening
- QPCR, digital PCR
- RNA sequencing
- Bioinformatic gene expression analysis
- Mass spectrometry
‘Research is more than an academic pursuit; it’s about helping people and giving hope.’
- Dr Sannu Thomas
- Dr Cristiana Mattei
- Dr Miaomiao (Cherry) Mao
- Dr Megan Oliva
- Dr Svetlana Paskas
- Dr Alita Aguiar
- Dr Pamela Kairath
- Dr Selvam Paramasivan
- Dr Jana Janaththani
- Dr Julia Lossef-Silver
- Dr Kristy Donnelly
Research and technical staff
- Alicia Sedo
- Helen Kopsidas
- Erlina Syazwan
- Shahnaz Khan
- Mao, M., Mattei, C., Rollo, B., Byars, S.G., Cuddy, C., Geza Berecki, Heighway, J., Svenja Pachernegg, Trevelyan Menheniott, Apted, D., Jia, L., Dalby, K., Nemiroff, A., Mullen, S., Reid, C., Snezana Maljevic 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:https://doi.org/10.1101/2023.02.14.528217.
- Heighway, J., Sedo, A., Garg, A., Eldershaw, L., Perreau, V., Berecki, G., Reid, C.A., 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, p.105622. doi:https://doi.org/10.1016/j.nbd.2022.105622.
- Burbano, L., Melody, Nikola Jancovski, Paymaan Jafar-Nejad, Richards, K., Sedo, A., Soriano, A., Rollo, B., Jia, L., Gazina, E.V., Piltz, S., Fatwa Adikusuma, Thomas, P.G., Kopsidas, H., Rigo, F., Reid, C.M., Snezana Maljevic and Petrou, S. (2022). Antisense oligonucleotide therapy for KCNT1 encephalopathy. JCI insight, 7(23). doi:https://doi.org/10.1172/jci.insight.146090.
- Rosa, F., Dhingra, A., Betuel Uysal, Mendis, C., Loeffler, H., Elsen, G.E., Mueller, S.G., Schwarz, N., Castillo-Lizardo, M., Cuddy, C.E., Becker, F., Heutink, P., Reid, C.M., Petrou, S., Lerche, H. and Snezana Maljevic (2020). In Vitro Differentiated Human Stem Cell-Derived Neurons Reproduce Synaptic Synchronicity Arising during Neurodevelopment. Stem cell reports, 15(1), pp.22–37. doi:https://doi.org/10.1016/j.stemcr.2020.05.015.