PhD Studentship

The Cell and Molecular Basis of Batten Disease
Department of Paediatrics and Child Health
University College London

Royal Free and University College Medical School
MRC Laboratory for Molecular Cell Biology

A PhD Studentship is available in the Department of Paediatrics and Child Health for 3 years to study the neuronal ceroid lipofuscinoses (Batten disease), a group of childhood neurodegenerative diseases. This project will further understanding of the basic neurobiological defect in Batten disease and the cellular function of the proteins mutated in these disorders, predominantly by subcellular investigations using electron microscopy. Methodology will also include light and confocal microscopy, cell culture, immunohistochemistry, protein biochemistry and molecular biology.

Ultrastructural studies in a murine model deficient for one of the genes mutated in this disease, CLN3, show that neurons die by a novel caspase-independent mechanism of programmed cell death associated with autophagy. The neuronal phenotype of this and models of five other types of NCL will be investigated to define the underlying mechanisms of neurodegeneration.

In addition the cell biological defect cause by loss of function of one of the proteins mutated in this disorder, CLN3, will be investigated in mammalian and yeast models. We have defined various lysosomal deficits in CLN3-deficient cells including a quantitative deficiency in endocytosis. A more detailed investigation of the role of CLN3 in the lysosome-endosome pathway and the exact nature of the defective internalisation pathway will be undertaken.

The Studentship is funded by the European Commission and fees will be paid at the home/EC rate (stipend is equivalent to MRC UK scale). The student will work in the laboratories of Dr Hannah Mitchison and Prof Dan Cutler of the MRC Laboratory of Molecular and Cell Biology, UCL.

Two copies of applications from candidates with at least a 2(i) honours degree (or non-UK equivalent) in a biological discipline, including a CV and the names and addresses of two referees, should be POSTED to Dr Hannah Mitchison, Department of Paediatrics and Child Health, Royal Free and University College Medical School, 5 University Street, London, WC1E 6JJ.

More information is available at http://www.ucl.ac.uk/paediatrics/ and informal enquiries are welcome - tel: 020 7679 6109, email: hmitchis@ucl.ac.uk.

The closing date for applications is Friday, 4th June 2004. UCL Taking Action For Equality.