Mechanisms of fever-induced epilepsy and related cognitive impairment
Dr G Brennan
Prof D Henshall
Monday, December 02, 2019
Competition Funded PhD Project (Students Worldwide)
Temporal-lobe epilepsy is a common chronic neurological disorder characterized by spontaneous recurrent seizures. Fever-induced seizures (febrile seizures) are the most common type of seizure in young children and are generally harmless. However prolonged febrile seizures and complex febrile seizures are associated with developmental delay, cognitive impairment and an increased risk of developing epilepsy in later life. Additionally up to one third of patients who develop epilepsy are resistant to current medical treatments and will experience uncontrolled seizures.
The disorder is also associated with a higher risk of developing anxiety disorders and depression as well as sudden unexpected death from epilepsy. There are currently no treatments for the prevention of adverse outcomes following a prolonged febrile insult during childhood and a real clinical need remains for the development of novel therapeutics which treat the underlying causes of the disease. The mechanisms by which prolonged febrile seizures cause cognitive impairment and epilepsy however remain poorly understood.
The current project will explore the role of a novel class of non-coding RNAs called microRNAs as a potential regulator of febrile seizure-induced cognitive impairment and subsequent epilepsy development. MicroRNAs are a class of small non-coding RNAs which negatively regulate gene expression by binding to target RNAs and blocking their translation. Previous work from our group and others has found that these molecules play an important role in temporal lobe epilepsy. Their role in febrile seizures however is as yet unexplored.
The project will employ a variety of innovative methodologies to explore the role of a novel class of RNAs in specific cellular populations to decipher the role of microRNAs in febrile seizure related epilepsy and cognitive impairment. Specifically we will develop a novel in vivo model of febrile seizures and combine with cutting edge cell specific RNA-sequencing and ChIP-sequencing approaches as well as subsequent intervention strategies.
The inter-disciplinary nature of this project (molecular biology, in vivo pharmacology and bioinformatics approaches) will provide the student with broad training and a unique skillset. The project will be incorporated into the SFI-funded FutureNeuro Research Centre where students will have access to world class research facilities and the chance to work within an integrated team consisting of scientists with diverse backgrounds as well as clinicians and e-health researchers.