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Research Fellows Directory

Rosemary Staniforth

Dr Rosemary Staniforth

Research Fellow


University of Sheffield

Research summary

Although the perception is that understanding the cause of brain diseases is generally beyond the scope of human endeavour, it is actually surprisingly refreshing to see the amount of knowledge that is being accumulated. It is becoming increasingly clear that the source of degeneration in old age may stem from common molecular problems. Proteins are large biological polymers, large chains of smaller building blocks called amino acids. Unlike other polymers, proteins form unique complex arrangements known as their fold or three-dimensional structure. When this goes wrong, and this happens increasingly in old age, protein molecules merge together to form assemblies that become toxic to human cells. I am currently studying a protein called cystatin for which I have developed a method in the test tube to reproduce these ageing problems. I have been measuring distances between different atoms in the cystatin protein molecules within these pathogenic assemblies. I have used a complex series of methods from genetic manipulation of microbes to NMR spectroscopy (a test tube equivalent to the MRI machine that looks at whole bodies) and X-rays of sulphur atoms. With the results, I have been able to test current ideas of how these pathogenic structures form and bring important insight into the nature of these assemblies. The structure is not as simple as some researchers have proposed but is certainly tractable. I have also focused my time and effort on developing methods to produce different molecular forms of these assemblies. I hope to examine how variants of cystatin and other key biological substances such as the membranes that make up the surface of biological cells modulate the assembly of the amyloid beta protein which is recognised as the principal cause of Alzheimer’s disease. I think the knowledge we will gain will not only provide us with new targets for the development of therapeutics but will provide us with the in-depth understanding of how these processes occur, a key element in focusing our search for a cure.

Grants awarded

Scheme: University Research Fellowship

Dates: Jan 2001 - May 2010

Value: £404,333.92

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