Bioorthogonal Labelling of Nucleic Acids – New Tools for Super-Resolution Imaging

Supervisors: Professor Mark Bradley (see also here), Professor Nick Gilbert

Project Description:

Understanding how mammalian cells function in normal development and disease is central to life science research, and is necessary to discover new drugs and treatments. To dissect the individual parts of this puzzle it is necessary to use specific labels that can be used to mark individual components. Over the last 30-years many different approaches have been used for labelling specific parts of the puzzle, often in different colours - different proteins can be labelled with specific reagents called antibodies that can be tagged in different colours and visualised by microscopy to explore how they relate to each other in 3D space.

Similarly this approach can be used on a molecular level to ask if these components interact with each other. However although there are very good tools for analysing proteins, in contrast it is much more difficult to separately label them, as they look/react very similarly.

We have recently shown that in cells, DNA is packaged with RNA and proteins to make a mesh that is important for regulating how cells function, but we lacked the tools to investigate this relationship.

Understanding these interactions is crucial as one of the proteins for making the mesh is often mutated in cancer, and genetic mutations in this protein cause developmental defects in children. Therefore, to understand how proteins, DNA and RNA work together as part of this PhD we will develop a new palette of reagents that will allow us to mark these different components in cells in different colours simultaneously.

This multiplex approach will be applicable to many different studies but will critically enable use to understand how individual components work together in regulating DNA and how in disease this can go wrong.

The PhD will develop innovative methods in chemistry and molecular biology which together will make new tools for understanding how life works. Thus the PhD would target a passion for organic synthesis – but involve direct biological application of the generated molecules.

If you wish to apply for this project, please go this link.

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