Dr Julian Thorpe, head of the Electron Microscopy Lab at the University of Sussex, will be working towards a better understanding of degenerative brain diseases thanks to a £247,000 grant from the Wellcome Trust. He is taking a very close look at a possible contributory cause of nerve cell death in a group of conditions related to Alzheimer's disease.
"Alzheimer's disease is characterised by 'plaques' which are outside the brain cells and also 'tangles' (marked * in the photo) which are inside the cells," says Julian. "In the group of diseases known as 'tauopathies' there are no plaques, except in Down's syndrome, but they do have the tangles."
The taupathies include Down's Syndrome, progressive supranuclear palsy (which Dudley Moore died from recently), Pick's disease, corticobasal degeneration, and frontotemporal dementia.
In Alzheimer's disease, a protein known as Pin1 interacts with the 'tangles', which consist mainly of 'tau' protein. These tangles are damaged remnants of the cell's supporting 'cytoskeleton' which correlate with the impaired nerve function that leads to dementia.
"Pin1 protein is normally predominantly in the nucleus (marked N in photo) of a cell where it helps to regulate cell division," says Julian. "In Alzheimer's disease it has been shown that Pin1 comes out of the nucleus to bind with the tau protein in the tangles, but it seems there isn't enough Pin1 in the cell to cope with all the tau."
As Pin1 acts as a kind of housekeeper protein, helping other proteins to carry out their normal functions, this shortage of Pin1 may be what leads to the death of brain cells.
"It seems this depletion of Pin1 in the nucleus contributes to the death of the cell and we're going to use electron microscopy and biochemical methods to investigate," says Julian. "Our hypothesis is that the Pin1 protein is involved in these diseases as it is with Alzheimer's disease."
Julian will be using a transmission electron microscope (TEM) to study human post-mortem brain samples. The other members of the team at Sussex are Reader in Biochemistry John Kay, Research Fellow Simon Morley, Research Fellow Stuart Rulten and Nigel Cairns from King's College London.