The centrosome has an important role in brain development, as demonstrated by the genetic links between microcephaly – a developmental disease where brain size is reduced – and centrosome proteins. This project will investigate how changes in centrosome proteins during evolution have contributed to the differences in brain development between humans and other animals.
In this project, we will use CRISPR-Cas9 to generate a series of zebrafish centrosome mutants. We will then complement these loss-of-function mutants (similar to knock-outs) with genes encoding human proteins and humanised zebrafish centrosome genes. Zebrafish is sufficiently close as a model system that we can extrapolate our findings and make valid anatomical comparisons. It is also sufficiently evolutionarily diverged from humans that it can act as a ‘clean’ background once its native genes are inactivated.
Confocal microscopy and immunohistochemistry will be used to determine the changes in zebrafish brain development that these combinations of mutations cause. Due to the rapid pace of zebrafish development, we can observe changes in brain development within the first three days of embryogenesis. Furthermore, the observed changes will be linked to centrosome function through cell biology studies. Ultimately, we aim to pinpoint the key changes, at the protein domain and amino acid level, in human centrosome protein evolution that contribute to characteristic human brain development.
To pursue this project, the applicant should have experience in either molecular biology, cell biology or embryology and developmental biology. Experience of zebrafish while desirable is not essential.
This project is a collaboration with Hunter Fraser’s research group at Stanford University in the US.
For further information and to apply follow link to https://www.royalholloway.ac.uk/studying-here/applying/postgraduate/how-to-apply/