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4 YEAR PhD IN NEUROSCIENCE

Mike Cheetham

Institute of Ophthalmology

Cell Biology of Neurodegeneration

Background
Many neurodegenerative diseases (e.g. Alzheimer’s, Parkinson’s and Huntington’s disease) are characterised by intracellular and extracellular inclusions of aggregated, misfolded protein. The presence of these inclusions suggests underlying problems of neuronal protein homeostasis (proteostasis) in these diseases. Our research aims to understand the consequences of protein misfolding and the cellular response to imbalances of proteostasis in a wide range of diseases from Retinitis Pigmentosa to Alzheimer’s disease. For example, molecular chaperones are key mediators of proteostasis and we have shown that the manipulation of molecular chaperones can alleviate protein misfolding, aggregation and cell death in both in vitro and in vivo models of neurodegenerative disease (1-3).

We use a multidisciplinary approach from the molecular through to whole organism studies. This combination of techniques allows us to examine the molecular and cellular processes associated with neurodegenerative processes. Contemporary cell biological techniques are the usual starting point before moving on to test the validity of our findings in other models of neurodegeneration. The overall aim of our research program is to help in the development of effective therapeutic strategies for neurodegeneration.

AVAILABLE PROJECTS

Research projects are based upon the research interests of the lab and are designed in discussion with individual students, specific projects currently underway in the laboratory include: neuronal specialisation of molecular chaperone function; imbalances of tau proteostasis; the ubiquitin proteasome system in Parkinson’s disease; molecular chaperone manipulation of ALS; molecular chaperones in the biogenesis, quality control and function of GPCRs, in particular rhodopsin; developing pharmacological therapies for retinitis pigmentosa; novel retinal disease gene characterisation

SELECTED PUBLICATIONS

Mendes, H.F. and Cheetham, M.E.  (2008)
Pharmacological manipulation of gain-of-function and dominant-negative mechanisms in rhodopsin retinitis pigmentosa.
Molecular Genetics 17(19):3043-54

Howarth J.L, Kelly S, Keasey M.P, Lee Y-B, Glover C.P.J, Mitrophanous, K, Chapple, J.P., Gallo J.M Cheetham M.E., and Uney J.B (2007)
Hsp40 molecules that target to the ubiquitin-proteasome system decrease inclusion formation in models of polyglutamine disease.
Mol Therapy, 15(6):1100-5

Westhoff. B., Chapple, J.P., van der Spuy, J., Höhfeld, J., and Cheetham, M.E.  (2005)
HSJ1 is a neuronal shuttling factor for the sorting of chaperone clients to the proteasome.
Current Biology 15(11):1058-64

More: https://iris.ucl.ac.uk/research/personal?upi=MECHE52

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