A new in vivo model of axon pathology in human tau mutants
Dr Vincenzo De Paola, Professor Maria Grazia Spillantini
A 3-year PhD studentship fully funded by Alzheimer’s Research UK is available in the laboratory of the Synaptic Plasticity and Repair Group of Dr Vincenzo De Paola at Imperial College London. The studentship is in collaboration with Professor Maria Grazia Spillantini in the Department of Neuroscience at the University of Cambridge. The project will make use of a novel in vivo system to study human neurons derived from patient stem cells with defined mutations in the tau gene. These mutations in people lead to widespread synaptic loss and neurodegeneration, for which there is no cure. The mechanisms of the synaptic and neuronal degeneration are unknown. However, Professor Spillantini has recently found that patient-derived neurons cultured in the dish already have defects during their early development, in particular in the axonal compartment (Iovino et al., 2015), which resemble the defects found in patients. The aim of the project is to identify new axonal and synaptic phenotypes in vivo, which can later be used to screen for drugs that rescue the defect in a more physiological environment than the culture dish. We use an interdisciplinary approach and facilities accessible for this project include setups for combined electrophysiological and imaging studies, with two 2-photon microscopes, all optical stimulation and activity recordings in awake animals, light-sheet and super-resolution microscopes including SIM, PALM, STORM and STED as well as stem cell biology facilities.
The golden triangle of London, Oxford and Cambridge is one of the largest and most vibrant neuroscience communities in the world, with outstanding seminars and opportunities for collaboration. Imperial College London is consistently rated among the world’s best universities with a reputation for excellence in neurotechnology and clinical neuroscience.
You will learn a variety of cutting edge imaging technologies including optogenetic and rabies virus-mediated circuit mapping, all optical stimulation and recording of activity, awake structural and functional longitudinal imaging (Holtmaat et al., 2009; Canty et al., 2013; Grillo et al., 2015) as well as human stem cell biology assays.
Candidates should have a background in cell and molecular biology or biochemistry with an interest in neurobiology.
How to apply
Applications, including CV, list of publications and statement of research interests should be sent to Dr Vincenzo De Paola at firstname.lastname@example.org. Applicants should arrange to have at least two confidential letters of reference sent by referees to this e-mail.