Combining live imaging, modelling and molecular genetics to understand transcriptional mechanism

点击翻译按钮获取中文摘要

For normal development and functioning of organisms, genes must be switched on in the correct place and at the correct time. In contexts where genes are not switched on correctly, or where genes are not on for the correct period of time, loss of cell function results, which can lead to devastating human diseases, such as cancer, neurodegeneration and developmental disorders. To study how the switching on and off of genes is controlled, we use a state-of-the-art technique, to directly watch single genes in living cells. Using a microscope, we can observe cells and assess whether a specific gene is on or off. We measure the number and duration of on and off periods and the variation in the strength of the on phase over time. We test how the on/off properties alter when cells are stimulated, and how they change over time as the cells develop.We compare these observations to simple computer simulations of gene behaviour, which are developed using rules we decide upon. When the computer fails to mimic the on/off behaviour of real genes, we learn that our rules are wrong, and need to be changed. When we have a set of rules which appears to work, we then make modifications to the actual genes, then watch and record how their behaviour changes. The rules we have developed should also apply in a predictable way to the modified gene, so if they do not, we know the rules are still wrong, and we need to further evaluate them. The process of adjusting and improving the set of rules forces us to continually develop a more complete understanding of how genes are controlled