The role of the ISR in childhood neurological disease
Research type
Research Study
Full title
The role of the integrated stress response in childhood neurological disease
IRAS ID
276268
Contact name
Liz Allen
Contact email
Sponsor organisation
Sheffield Hallam University
Duration of Study in the UK
3 years, 11 months, 31 days
Research summary
Genetic testing is becoming an everyday part of the healthcare system. However, as more genetic testing results are available, scientists need tools to understand how the changes that we find are linked to the patient’s symptoms. To do this, we need to develop new laboratory tests which let us test out whether a DNA change is stopping cells from working properly.
eIF2B is a protein which helps to read the instructions in our genes and turn them into the proteins that make up our bodies. When our bodies are put under stress, like being unwell, eIF2B helps to protect our cells by putting them into hibernation. This is called the integrated stress response (ISR). When the stress goes away, the cells wake up and carry on doing their normal jobs. Sometimes this goes wrong and the cells don’t wake up and eventually die.
Most cells in our bodies are continually growing and replacing themselves. But the cells which make up our brains do not normally do this. So when the ISR isn’t working properly, brain cells are permanently lost, and people develop neurological or brain diseases.
Research has found that the ISR works differently in patients with rare genetic brain diseases. In the lab we have shown that the eIF2B protein forms patterns inside brain cells. We think that looking at eIF2B patterns and cell stress can help us to understand how DNA changes are causing patients' cells to die. We will look at the eIF2B pattern in skin cells donated by people who have genetic brain diseases to see if it changes. We will then collect skin samples from current patients to see if we can see the eIF2B pattern in these cells. Hopefully the eIF2B pattern will be a diagnostic test which would work for different very rare diseases.
REC name
East of England - Cambridgeshire and Hertfordshire Research Ethics Committee
REC reference
21/EE/0188
Date of REC Opinion
1 Oct 2021
REC opinion
Further Information Favourable Opinion