Investigating the biological roles of oxidised forms of 5-methylcytosine and active

Thanks to the fascinating development and developmental disorders module during my undergraduate
course in Biochemistry and Genetics, I became very interested in pursuing a career in scientific research.
Accordingly, in my final year project, I studied the structure - function relationship of def6 gene (encodes a
novel GEF for Rho GTPases) that was implicated in cell shape, polarity and movement but the mechanism
was unclear. By applying molecular biology, cell culture, transfection and imaging techniques I showed using
COS-7 cells that the PH-like domain encoding N-terminal region of DEF6 protein is essential for its proper
subcellular localisation and function. Although caring for an ill family member impacted my degree
classification, it enhanced my resolve to pursue a career in biomedical research. As a result, I applied for
and won a very competitive MRC funded MSc studentship in Stem Cell Technology. With this excellent
opportunity, I have not only gained the highly relevant theoretical knowledge and practical skills of
isolating, culture, expansion, and the differentiation of stem cells in the derivatives of all three germ layers,
but more importantly, I have learnt how to formulate an interesting biological question, employ the right
approach to tackle it, while appreciating the limitation of such an approach. By employing these skills,
during my MSc thesis, I was able to successfully show for the first time 1- The spatial distribution and
genomic localisation of 5mC oxidation derivatives,5-hmC and 5-caC in the developing brain, 2- These 5mC
oxidation derivatives transiently accumulate to epigenetically reprogram neural stem cells undergoing
neural to glial switch and 3- The transient accumulation of these 5mC oxidation derivatives serves as
intermediates in an active DNA demethylation process during lineage specification of NSCs.
From the quantitative analysis of these observations to the reporting of our findings Cell Reports I learned
additional highly relevant skills including how to; experimentally and statistically evaluate whether an
observation is significant, review the literature, discuss my observations and successfully go through the
challenging review process and present them to my peers. I have drawn on these skills in my book chapter
contribution.