Connecting European Neuroscience

Ph.D. Student in Leicester/UK

05 December 2017

Ph.D. Student in Leicester/UK

Job ID
14434
Place
Leicester/UK

Description

Neurodegenerative disorders occur when neurons malfunction and die more quickly and extensively than during healthy aging. These disorders have become one of the hallmarks of an increasingly aging population. Nitric oxide (NO) is involved in a multitude of cellular pathways with crucial functions in physiology, but can also promote nitrosative stress during pathological conditions and brain aging. Multiple neurodegenerative diseases, including AD, are exacerbated by abnormal NO signalling associated with increased NO-mediated post-translational modifications, such as 3-nitrotyrosination (3-NT). The mechanistic link between these abnormalities and disease pathogenesis is not clear. In order to address this deficiency, this project will investigate how 3-NT signalling affects protein function, as well as its effects upon neuronal function, whole animal behaviour and survival. The aim of this work is to identify protein targets to mitigate pathology at the synapse. We will test the hypothesis that 3-NT contributes to neurodegeneration by compromising synaptic functions and that this aberrant signalling induces neuronal decline associated with AD. The project will further explore approaches to minimise 3-NT levels and to monitor consequent effects on phenotypes associated with neurodegeneration and neuronal dysfunction. For this work, we will employ our expertise in Drosophila physiology, genetics and behaviour. This model system provides unique advantages to apply techniques such as electrophysiology, live-imaging, biochemistry and whole animal behaviour and survival studies.

Aims:
1: Identify functional consequences of NO signalling at the Neuromuscular Junction (NMJ) synapse
2: Identify the contributions of NO to AD-relevant phenotypes

This project will employ different approaches including electrophysiology to assess synaptic release and vesicle pools, life confocal imaging (FM1-43, FRAP, Ca2+) in addition to using various genetic modifications in Drosophila.

Job Information

Closing date:
2018-12-01
Employment start date:
2018-09-24
Contract length:
3 years
Institution:
MRC
Department:
Toxicology

Contact Information

Joern Steinert
Joern R Steinert, PhD
Programme Leader
MRC Toxicology Unit
Hodgkin Building
Lancaster Road
University of Leicester
Leicester LE1 9HN
UK

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