Targeting post-translational modifications to disrupting the function of secreted proteins

Targeting post-translational modifications to disrupting the function of secreted proteins

Project details

Modern drug discovery efforts are enabled by new therapeutic modalities that target proteins for destruction rather than simply inhibiting them (e.g. PROTACs). Building on this concept, we are developing molecules that block a range of post-translational modification processes in the cell to disrupt a protein’s function by driving its mislocalisation and destabilisation. This approach is particularly promising for drug targets that transit through the secretory pathway.

The project will involve the chemical synthesis of new molecular probes, which will be guided by structural biology, and the evaluation of these compounds against their targets and closely related enzymes. These probes will also be evaluated against a range of tumour cell lines at the Institute. This is an excellent opportunity for those interested in chemical biology.

 

About our research group

Many proteins are modified by diverse and complex glycan molecules, which modulate protein folding, trafficking, half-life and function. The Goddard-Borger Lab studies the role of these modifications, as well as the proteins that read, write and erase them, in diseases as diverse as malaria (Goddard-Borger and Boddey, Nature Communications, 2017, doi.org/10.1038/s41467-017-00571-y), COVID-19 (Williams & Goddard-Borger, Biochemical Society Transactions, 2020, doi:10.1042/BST20200505) and other respiratory diseases (Goddard-Borger, Nature Communications, 2020, doi:10.1038/s41467-020-16223-7). 

We use chemical, molecular and structural biology techniques to do this, which provides students an opportunity to gain practical skills in all of these fields with a high level of support from senior researchers. We collaborate extensively and welcome individuals who want to work as part of a diverse team to achieve significant research goals.

 

 

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