Exosome biogenesis and organelle trafficking in neurodegeneration.

Scientific summary: Intracellular transport pathways are fundamental for cell structure and function. Due to their longevity, complex morphology (long axonal and dendritic extensions) and requirement to maintain synaptic transmission, neurons are heavily dependent upon intracellular transport. Consistent with this, defects intracellular transport are directly linked to common forms of neurodegeneration. For example, altered function of the Rab activating protein C9orf72, a regulator of intracellular transport and subject of this project, are the major cause of genetic motor neurone disease (MND) and frontotemporal dementia (FTD).

Thus, this project will investigate how intracellular transport impacts neurodegeneration with the below aims:

1.      Identify transport pathways controlling exosome biogenesis and secretion in neurones.

2.      Investigate transport defects in C9orf72 deficient motor neurones.

Lab environment: the laboratory is located in the QMC Medical School campus of the University of Nottingham and is co-located and integrated with other groups actively investigating other areas of neurodegeneration, neurodevelopment and biochemistry. With activities such as shared group meetings and presentations.

Techniques and training opportunities: the project will involve a wide variety of current molecular and cellular biology technologies including; confocal microscopy, electron, mass spectrometry, sub-cellular localisation of molecules, protein-protein interactions, bioinformatics, statistics, gene cloning, cell biology, tissue culture, CRISPR, biochemistry and proteomics. Finally the student will have the chance to present their research at conferences in the UK and overseas.