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  Redefining epilepsy treatment - the role of waste clearing in the brain


   Biotechnology

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  Dr Janosch Heller  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

The Astrocyte Lab, School of Biotechnology, Dublin City University (AstrocyteLab) is seeking to appoint a PhD student to perform research focused on identifying novel therapeutic interventions to combat changes to brain waste clearing mechanisms in epilepsy.

Epilepsy is a chronic disease of the brain that accounts for a significant proportion of global disease burden, affecting between 4 and 10 per 1000 people. The disease is characterized by recurring bursts of electrical activity named seizures, which affect how the brain works. Common anti-epileptic drugs are ineffective in about a third of patients, highlighting the need for new treatment options. All common anti-epileptic drugs target neurons. However, epilepsy also affects other cell types in the brain. One of those cell types are astrocytes, which are essential for the correct functioning of the brain. For example, astrocytes help neurons with information processing, they clean up brain debris, and they hold neurons in place. All these functions are disturbed in the epileptic brain. Recently, astrocytes have also been found to be involved in the brain’s waste clearing system. Also this function is potentially disturbed in epilepsy. When waste accumulates in the brain this can lead to the development of further brain diseases such as Alzheimer’s disease. Hence, targeting astrocytes could be a new therapeutic strategy, to prevent seizure generation and to prevent the development of further brain diseases.

This project utilises a multidisciplinary approach combining expertise in bio imaging, molecular biology and neuroscience applied to rodent models of epilepsy, thus giving significant insight into (i) our fundamental knowledge of epilepsy pathophysiology and (ii) novel therapeutic strategies. In this project, we will use a combination of advanced fluorescent microscopy techniques (super-resolution, light-sheet and 2-Photon) to determine the damage to astrocytes, the blood-brain barrier (BBB) and the brain’s waste clearing system in rodent models of epilepsy. Additionally, we will generate virus-based gene therapies specifically targeting astrocyte functions that are disrupted in the epileptic brain. Our research has the potential to change our approach to treatment of epilepsy, and would significantly improve the care of patients with treatment-resistant epilepsy.

Applicants are invited with experience in the areas of neuroscience, physiology, biophysics, cell biology, biochemistry, or a related discipline. Applicants should have a strong interest in translational research as this project focuses on developing novel therapeutics to treat epilepsy. Key techniques in this project include rodent models of epilepsy, primary cell culture, molecular biology, immunolabelling, super-resolution and other fluorescent microscopy (both in fixed specimen and in vivo) as well as in vitro modelling of the BBB.

Start date: 01st September 2022 or shortly thereafter.

The PhD student will be supported by a stipend of €18,500 + fees for 4 years.

Informal enquiries to Dr Janosch Heller, [Email Address Removed], School of Biotechnology, DCU (Janosch Heller).

How to Apply: The candidate should apply directly to [Email Address Removed] along with a detailed CV, short cover letter, and names and email addresses of two referees.

The closing date for receipt of completed applications is Thursday, 14th July 2022. Interviews will be held via Zoom on Friday, 22nd July 2022.


Biological Sciences (4)

Funding Notes

Stipend of €18,500 + fees for 4 years

References

Christian Henneberger, Lucie Bard, Aude Panatier, James P. Reynolds, Olga Kopach, Nikolay I. Medvedev, Daniel Minge, Michel K. Herde, Stefanie Anders, Igor Kraev, Janosch P. Heller, Sylvain Rama, Kaiyu Zheng, Thomas P. Jensen, Inmaculada Sanchez-Romero, Colin J. Jackson, Harald Janovjak, Ole Petter Ottersen, Erlend Arnulf Nagelhus, Stephane H.R. Oliet, Michael G. Stewart, U. Valentin Nagerl, Dmitri A. Rusakov (2020) LTP Induction Boosts Glutamate Spillover by Driving Withdrawal of Perisynaptic Astroglia. Neuron 108 (5): 919-936.e11
https://doi.org/10.1016/j.neuron.2020.08.030
Natalija Aleksejenko, Janosch P. Heller (2021) Super-resolution imaging to reveal the nanostructure of tripartite synapses. Neuronal Signal 5 (4): NS20210003.
https://doi.org/10.1042/NS20210003
Janosch Peter Heller, Tuamoru Odii, Kaiyu Zheng, Dmitri A. Rusakov (2020) Imaging tripartite synapses using super-resolution microscopy. Methods 174: 81-90
https://doi.org/10.1016/j.ymeth.2019.05.024