PhD student profiles


Thomas Peskett
Wellcome Trust 4-year Interdisciplinary PhD Programme, beginning in Autumn 2013

Project title
Cell toxicity and polyglutamine aggregates in Huntington's disease

Principle investigators: (Supervisor: Professor Helen Saibil; Co-supervisor: Dr Alan Lowe)


Before coming to London I studied chemistry at Cardiff University. My final year at Cardiff was spent in the lab of Prof Kenneth Harris where I carried out a research project aimed at exploring how different crystal forms (polymorphs) develop. We did this by using powder X-ray diffraction to characterise a family of urea-containing co-crystals that were able to form polymorphs depending on the crystallisation conditions.

I then spent a short placement in a hospital biochemistry lab before moving to London to do an MRes at UCL, supervised by Dr Chris Kay and Dr Cara Vaughan, where we determined how the molecular flexing of the chaperone Hsp90 is changed by the binding of one of its co-chaperones using spin-labelling and electron paramagnetic resonance experiments.

Rotation projects

Rotation 1 (Dr Andrew Martin)
Computational modelling of the structure and dynamics of human Hsp90

Rotation 2 (Prof Helen Saibil)
Polyglutamine aggregation and toxicity in a yeast model of Huntington's disease

Rotation 3 (Dr Alan Lowe)
Single-molecule fluorescence microscopy of huntingtin aggregates

PhD Project

Most proteins must adopt defined structures in order to function properly. When misfolded forms of a protein accumulate, as is the case in many neurodegenerative diseases, the protein can lose its ability to function normally or may gain new, toxic functions. Protein misfolding is typically associated with aggregation. While misfolding and aggregation have been studied extensively, it is still unclear exactly how aggregates or the aggregation process are related to cell toxicity.

Our aim is to study these processes at high resolution in cells. For my PhD project I am using correlative light and electron microscopy to determine the nanoscale structures of protein aggregates in the cell. We are combining these structural analyses with single-molecule fluorescence microscopy to try to understand how aggregate structure, formation and sub-cellular localisation are linked to cell toxicity and hopefully contribute to our understanding of the cellular mechanisms underlying neurodegenerative diseases.

Above: Electron microscopy of budding yeast cells that have been high-pressure frozen, freeze-substituted and sectioned. Evidence of the electron beam can be seen as faint rings where imaging has taken place




Institute of Structural and Molecular Biology, University of London
ucl logospacerbirkbeck logo