How do genes work?

Lead Investigator: Dr Keith Spriggs
PhD student: Alexandra Hughes
Institute: Nottingham University
Grant type: PhD studentship
Grant amount: £75,000
Start date: October 2010
Completion date: September 2013

Scientific Title: Investigating the translational control of genes involved in Alzheimer's disease

What was the project, and what did the researchers do?

Genes do not always act in isolation – they often respond on signals to 'switch on', or become more or less active. This enables the activity of a gene to respond to its environment and the demands of the cell.

This project investigated the ways that genes associated with Alzheimer's disease are regulated.

Understanding what signals regulate genes associated with Alzheimer's disease is critical for understanding why these genes are associated with the disease, and as avenues for potential new treatments.

Some of these genes may lead to neurodegeneration, whilst others may be neuroprotective – understanding both types will lead to a lot more understanding of the underlying changes that occur in the brain during the development of Alzheimer's disease.

What were the key results, and how will this help in the fight against dementia?

As a result of this project, the researchers have been able to show that a number of genes associated with Alzheimer's disease are controlled using similar mechanisms, and that the activity of these genes is increased in response to cellular stresses, for example oxidative stress, which have been proposed as risk factors for Alzheimer's disease.

They have also learned something about the way that neprilysin, a protein that clears amyloid deposits, is regulated differently depending on the conditions within the cell. This will allow the researchers to target their research towards finding ways to increase neprilysin expression in neuronal cells in Alzheimer's disease, independently of the potentially 'stressed' conditions of the cells.

What happened next? Future work and additional grants

Dr Spriggs plans to continue to investigate the control of genes associated with Alzheimer's disease, with particular focus on identifying and exploiting novel drug targets.

Alex Hughes, the PhD student on this project, is currently writing up her PhD thesis (Jan 2014) and hopes to continue her scientific career in the near future.

How were people told about the results? Conferences and publications

Poster presentations:

Translation UK 2011, 2012, 2013 

Alzheimer’s Society Research Conference 2011 

Alzheimer’s Research UK 2012.  

Oral presentations:

Alzheimer’s Research UK Network meetings 2011, 2013.