David Vaux

Molecular pathology of post-translational modification

The group is interested in the molecular mechanisms by which pathological perturbations in the post-translational modifications of proteins (including proteolytic maturation, oligomeric assembly, ubiquitination, phosphorylation and fatty acyl modification) can lead to severe human disease. Conditions resulting from defective or altered post-translational modification are extremely diverse, ranging from Alzheimer’s disease, Type II diabetes, neural tube defects, lipodystrophy and cardiomyopathy, to tumour metastasis and premature ageing syndromes.

The nucleoplasmic reticulum in a human cell (amin B, green, lamin A red).

Surfactant amyloid precursors assemble to generate fibrils and channels.

To study these processes, we employ a wide range of experimental techniques, often linking large-scale genome or proteome-wide analysis to more targeted experiments to analyse the role of specific perturbations in generating a particular phenotype. We use mRNA and miRNA microarray analysis to follow gene expression, and its regulation by non-coding RNAs, as well as whole cell or organelle-selective proteomic analysis to identify changes at the protein level, whether in protein abundance or post-translation modifications. We couple these large-scale screens with analysis of phenotypes detected biochemically or by quantitative imaging. We use live cell tracking for cellular behaviours such as migration, or examine fixed specimens for detailed morphological analysis by light or electron microscopy (including ion beam methods such as NanoSIMS).

We also examine the consequences of altered protein structure at the biophysical level, linking cellular changes to molecular assembly processes generating toxic oligomers, fibrils or hydrogels. These experiments are guided by theoretical modelling in collaboration with physicists, and include electrophysiology, spectroscopy, surface and bulk rheology, surface tension measurement, and a wide range of imaging techniques on interfaces, model membranes and liposomes.

Relevant Publications

Trigg BJ, Lee CF, Vaux DJ and Jean L
2013

Biochem J 456: 67-80.

Lee CF, Bird S, Shaw M, Jean L and Vaux DJ
2012

J Biol Chem 287: 38006-19.

Coene ED, Gadelha C, White N, Malhas A, Thomas B, Shaw M, and Vaux DJ
2011

J Cell Biol 192: 497-513.

Malhas AN, Goulbourne CN and Vaux DJ
2011

Trends in Cell Biology 21: 362-73.