Gene expression profiling of the response of motor neurones to physiological and environmental stress

Reference Code: Kirby/Oct05/6212
Grantee: Dr J Kirby
Grantee Institution: University of Sheffield
Duration: 3 years
Amount: £59,500 (MND Association Prize Studentship)

Description:

Janine Kirby with the machine used to scan DNA

What this research means to you: It is thought that most cases of MND occur as result of a combination of environmental factors and subtle variations in certain genes known as “susceptibility genes”. This project aims to identify potential susceptibility genes and then find out if certain variations of those genes are found more often in people with MND than in the general population. Identifying susceptibility genes for MND will help scientists understand some of the mechanisms of the disease and will ultimately help with drug development.

The researcher explains in detail: “The initial aim of the project is to identify the genes that are being switched on or off in the motor neurones (MNs) of mice, when the mice are either exercise trained or treated with low oxygen levels, termed hypoxia. We believe that sporadic MND may arise from changes in the DNA sequence of genes, such that the proteins that are made from these genes either do not work as efficiently, or do not respond to the environment within the cell in the normal way. We suspect that these changes in the DNA sequence increase the risk of developing MND when associated with other environmental factors, such as exercise and hypoxia. MNs will be isolated from the spinal cord of the mice and the genes being switched on or off in response to exercise or hypoxia detected using microarrays – glass slides containing thousands of spots of DNA which together represent almost all of the functional genetic blueprint of the mouse. Copies of the genes switched on in the MNs pair up with their matching DNA spots on the microarray. Using a laser to scan the glass slide, we can then determine those genes that are switched on, and by how much, compared to MNs from un-exercised or untreated mice. Several natural variations of some of these genes may exist. The next stage will be to see if a particular variation is found more frequently in individuals with sporadic MND, than in the normal population. Ultimately, identifying specific risk factors for sub-groups of people with sporadic MND will help develop specific drug therapies, or may identify a “one for all” treatment in a common pathway affected in all types of MND.”