Identifying common molecular mechanisms underpinning nervous system stability in health and disease

Through the human lifespan, the nervous system grows, develops, stabalises and in some regions begins to decline. The factors governing the stability of the nervous system as we age, and indeed its susceptibility to neurodegeneration inducing stimuli remain unclear.

Many neurodegenerative conditions share a range of common pathophysiological hallmarks such as cellular accumulation of abberent and/or missfolded protein and/or metabolic byproducts, and regionally selective neuronal loss. Neurodegeneration can be caused by a range of potential inititating factors from clear cut genetic triggers, through to envenoming toxins.  The onset of such neurodegenerative conditions can be associated with advancing age such as Alzheimer’s disease, frontotemporal dementia, vascular dementia, and dementia with lewy bodies  to name a few examples for which there are few genetic associations. They can also occur as dementias of childhood (i.e. Batten disease, Neimann-Pick, Sanfilippo syndrome etc)  which are all genetically mediated. One of the key questions in neurodegenerative research is what is it about certain brain regions which makes them more or less susceptible to a neurodegeneration inducing stimuli?

The project proposed here would aim to identify specific protein cascades which correlate and (in some cases) regulate neurodegenerative disease processes invivo. At NTU we have state of the art mass spec capabilities, invivo and human tissue resources which would allow us to address this.

The successful applicant would have the opportunity to shape the project as it develops and would receive appropriate training in experimental design including the use of post mortem human tissues, sample handing and preparation for mass spec, handling large data sets, pathway analysis including predicting potential regulators hubs, and invivo work with simple model organisms.

Supervisory team

References

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