The Science

Everything we do, from breathing to thinking, is dependent on protein molecules.  Proteins are formed by the linking together of smaller molecules - amino acids - into large stuctures that then fold into complex shapes, allowing them to work together to perform life's functions. 

When proteins misfold they are unable to fulfil their intended roles and instead clump together to form amyloid plaques: this is what causes diseases such as Alzheimer’s, Parkinson’s and Type 2 diabetes.

Amyloid plaques were first discovered as deposits in the brains of sufferers of dementia in 1906 by the neurologist Alois Alzheimer. Until the 1990s it was believed that only very few, defective, proteins were susceptible to such misfolding. Professor Sir Christopher Dobson showed that in reality the amyloid state is one that almost any ‘normal’ protein can occupy; a breakthrough that reframed the thinking around how the resultant diseases can be prevented and treated.

Chris began his career applying nuclear magnetic resonance (NMR) spectroscopy – a method for analysing the molecular structure of a substance – to proteins. When one of his postdocs left a ‘normal’ unfolded protein in a spectrometer over a long weekend and returned to find that it had turned into a gel, Chris’s interest was piqued. On closer inspection it transpired that the ‘perfectly ordinary’ protein had misfolded into an amyloid structure, hitherto only known from descriptions of disease and in contradiction of the prevailing wisdom that only a few defective proteins were able to misfold in this manner.

Knowing that ‘normal’ proteins could misfold with relative ease begged a further question: why are protein-misfolding diseases not more prevalent? This led Chris to hypothesise that our bodies must have a means of preventing misfolding and keeping proteins in their functional states, and that it is a failure of these protective mechanisms that clears the way for protein misfolding diseases. For Chris, this was a welcome hypothesis as it suggested that ‘the disease-causing aggregates do not fight back and evolve like bacteria and viruses but are due to a lack of control in our normal housekeeping methods. They could, in principle, be easier to treat than many typical viral diseases, heart disease or cancer.’

In recent years Chris in fact did turn to drug discovery, screening a variety of agents for their ability to prevent the formation of toxic protein aggregates. Encouraging laboratory results suggest that this approach could transform the prevention and treatment of the diseases of ageing.

 

"Chris was a true pioneer, bringing chemical thinking and methodology to a biological problem and inspiring a whole generation of scientists"

Professor Andrew Hamiltion (1976), St John's Honorary Fellow and President of New York University

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