Progeria Research at Brunel
The scientists at Brunel are a husband and wife team. Dr Ian Kill is an expert on cellular and organismal ageing and Dr Joanna Bridger an expert on nuclear structure and organisation. Both had worked on the protein lamin A previously and so were in an excellent position to pursue this collaborative effort. Cells derived from patients with HGPS were purchased from America and the couple set about deciphering how these cells age in culture and the link between nuclear structure and premature ageing.
When growing the cells in culture they did not behave as expected. To begin with, the cells actively divided very rapidly much faster than cells in normal cultures. Then, towards the end of their life-span many of the cells died through a process known as apoptosis.
As the cells aged and had divided a number of times it became obvious that the cellular nuclei were damaged and had increasingly peculiar and abnormal shapes.
Along with this, lamin A protein was mislocalised from its normal nuclear localisation and an increasing number of cells without any lamin A at all accumulated. Cell death was probably due to the effects of losing lamin A in these cells.
What then is the link between the behaviour of these cells in culture and premature ageing of children suffering from HGPS? Most normal cells are only able to divide a set number of times and then loose the ability to divide forever but remain alive. Many scientists believe that this process, known as “cellular ageing”, is a major contributory factor in the normal ageing process within the body. The finding that HGPS cells use up their potential for division much faster than normal cells and then die is likely to be at the heart of the process leading to premature ageing in children suffering from HGPS. Certain tissues, such as skin, tendons and blood vessels, continuously replace worn-out or damaged cells. The cells used to replace the worn-out or damaged cells arise through cell division of existing cells. In HGPS this process may be compromised because firstly, cells are dividing too quickly and secondly that the very process of cell division leads to cell loss through apoptosis. Therefore, there would not be sufficient cells to support the normal function of the affected tissues.
The outcome of this research will help in understanding HGPS, how its symptoms can best be treated and will lead to further research aimed at designing a much-needed cure. Furthermore, understanding premature ageing will help us to understand normal ageing and aid in increasing the health-span of aged individuals.
Dr Ian Kill teaches Cell Biology and Dr Joanna Bridger teaches Developmental Biology in the Centre for Cell and Chromosome Biology, Division of Biosciences at Brunel University. Both head active Research Laboratories.
|
|||||||||
