Archie Wallace

PhD thesis:

A systems pharmacology view of disease-related variation in GPCRs

G protein-coupled receptors (GPCRs) regulate fundamental processes like vision, metabolism and immunity. Additionally, GPCRs are the main target for current clinical drugs. However, understanding how mutations present in the human population affect GPCRs to generate different drug response is still challenging. This PhD will build on previous work in the host lab combining GPCR structural analyses, systems pharmacology modelling, molecular pharmacology validation and pharmacogenomics data mining to explore which disease variants affect metabolic GPCR signalling, including key genetic obesity targets. By using these receptors as a case study, our results will support using systems pharmacology to develop personalised treatments informed by genetics meaning more receptors can be included in later studies. Additionally, by validating our novel hypotheses about previously uncharacterised GPCR variants in molecular pharmacology experiments, and using data from UK Biobank, we will be able to translate these hypotheses to more personalised therapeutic strategies to combat the obesity epidemic.

Who or what inspired you to pursue your research interests?

I have been inspired to pursue my research interests in precision medicine and pharmacology by speaking to those working in the precision medicine area including clinical doctors and academics who have all shown me that precision medicine may offer a sustainable solution to our public health crisis. Across my studies I have also been inspired to learn more about pharmacology. Through engaging with the general public, I have been inspired by the enthusiasm of people to get informed about their health. Pursuing my research interests in these areas will allow me to continue talking to the public about precision medicine.