The X-files: Our Amazing Inactivating X Chromosomes
When I was 17 I had the opportunity to spend some time in a real lab and it was fantastic. From that time on I knew I had to be a scientist. When I read about the Royal Society Partnership Grants I thought this would be the perfect opportunity to give some A-level science students the same opportunity. Together with my friend, ex-scientist and biology teacher at Hitchin Girls School, Dr Carla Jones, I successfully applied for one of the grants.
Six young women currently in year 12: Fiona, Ria, Immy, Sannojah, Corrine and Molly, spent five days in the lab with me to begin our project investigating X chromosome inactivation. Early in embryonic development one of the two X chromosomes in female mammals is inactivated resulting in genes on this chromosome being switched off. We can model this in the lab using female embryonic stem cells as they differentiate. Our aim was to correlate epigenetic changes (ie those that occur on top of DNA without changing the underlying sequence) detected on the inactive X chromosome with genes being switched off as the cells differentiate.
We were able to visualise the inactive X chromosome down the microscope using a fluorescently labelled antibody that detects repressed or switched off genes. To complement this, we generated RNA-seq libraries from undifferentiated cells with two active X chromosomes, and differentiated cells with one active and one inactive X chromosome. This technique allows us to detect which genes are switched on and which are switched off. We then analysed the data at a bioinformatics session back at Hitchin Girls School. We were able to see gene expression on the X inactive chromosome decrease as well as detecting other differentiation associated gene expression changes throughout the genome.
All six girls were totally engaged with the project from the beginning. Throughout my time with them they constantly asked questions and sought to understand everything they were doing. It was a wonderful experience for me to see them be amazed by things I take for granted after 13 years in the lab! They were particularly astonished by the fact that the embryonic stem cell line we were using was derived in 1994 and so was older than them!
My time with the girls culminated in a trip to the Royal Society for the Partnership Conference. The girls presented their data in front of a large audience and then at a poster session. I couldn’t help feeling proud watching their animated faces as they enthusiastically answered questions from Royal Society fellows at the poster session. These bright young women are clearly fascinated and excited by science and I am really pleased that I got the chance to show them what life a scientist is like and to share and discuss my research with them.
One further exciting aspect of this project is that Hitchin Girls School now have RNA-seq data and Seqmonk software installed on the school computers. This gives them a unique resource that they can use for many years to come, introducing young biological scientists to analysis of genome-wide data long after our stand alone project has ended.
(Thanks to Myriam Hemberger, Laura Woods, Natasha Morgan, Wendy Dean, Courtney Hanna, Simon Andrews and Kristina Tabbada for pitching in with the project)