The role of inheritance and the EGF pathway in mis-segregation of chromosomes during mitosis. (360G-Wellcome-207266_Z_17_Z)
I am proposing to research how the mis-segregation of whole chromosomes during mitosis impacts future cell divisions and how this is coupled to spindle assembly pathways and epidermal growth factor (EGF) signaling. During this project I will investigate whether a gain or loss of a chromosome, due to mis-segregation, predisposes daughter and grand-daughter cells to further segregation errors. Additionally, I will research whether the inhibition of EGF signaling will exacerbate chromosomal mis-segregation. The research will be carried out on non-small cell lung cancer (NSCLC) cell lines, which will be transfected with GFP-CENP-A, marking kinetochores, or GFP-tubulin, marking the spindle, and treated with SiR-DNA, allowing visualisation of chromosomes. These fluorescent reporter constructs will allow chromosomal mis-segregation and spindle geometry to be observed during live cell imaging. The live-cell imaging experiments will then be repeated in the presence of Gefitinib, allowing observations to be made whilst EGF signaling is inhibited. The primary goals of this research are firstly being able to provide key insight into how the EGF pathway regulates chromosomal instability (CIN) and cell fates in NSCLC, and secondly to be able to establish how the mis-segregation of whole chromosomes impacts future cell divisions.
Where is this data from?
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