Defining the role of kindlin-1 in the regulation of microtubule stability and mitosis (Brunton 1)Completed
|Project lead||Prof Valerie Brunton|
|Organisation||The University of Edinburgh, Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, Edinburgh, UK|
|Project budget||GBP 191,838.00|
|Start date / Duration||01. Sep 2014 / 37 months|
|Funder(s) / Co-Funder(s)||DEBRA UK, MSAP/EBEP Recommended|
|Research area||EB genetics, epigenetics & biology|
Short lay summary
Kindler syndrome (KS), named after the doctor who first described it, is a type of Epidermolysis Bullosa (EB) in which the skin is fragile, sensitive to light and blisters in response to trauma. As the person ages, their skin becomes thin, making it vulnerable to damage. Patients with KS are also more susceptible to developing a type of skin cancer called squamous cell carcinoma. KS is caused by inheriting a fault in a gene called KIND1 (or FERMT1) which normally controls production of a protein: Kindlin-1.This particular protein is important in the processes of cell division (known as mitosis) and growth in skin cells. The faulty gene will produce a Kindlin-1 protein that does not function properly, contributing to the thin and fragile skin. However, the way in which Kindlin-1 contributes to these processes at the molecular level is not yet fully understood.
Aims of the Research
It is understood that Kindlin-1 is an ‘adaptor’ protein, which means that it functions by binding to other proteins in the cell. This project wanted to understand how Kindlin-1 interacts with other proteins involved in cell division. The group has techniques available in their laboratory that has enabled them to identify which proteins interact with each other and also where inside the cell the interactions take place.
Normal skin cells were compared with those from people with KS to gain insight into the steps in cell division that are not functioning properly in KS skin. Work to increase our understanding of how Kindlin-1 functions contributes to our ability to devise ways in which we can treat this disease.
“Our research has identified how Kindlin-1 controls important processes in cells that allow them to grow and also protect themselves from UV damage. We now need to understand how we can restore these processes in people with KS to provide much needed treatments.”