I began my journey in research by studying Biomedical Science at the University of Newcastle where my interests lay in Immunology and Neuroscience. This led me on to study Translational Neuroscience (MSc) based at SITraN at the University of Sheffield. During my laboratory project I investigated the role of double-stranded DNA breaks in the molecular mechanisms that underlie seizures in zebrafish. My interest in Neuroscience and the experience I gained of working with zebrafish led me to embark on my PhD that involves screening small molecule libraries, with the aim of identifying hits that rescue ear and myelination defects in adgrg6 zebrafish mutants.
The GPCR superfamily includes targets of many known drugs, but also retains enormous potential for future drug discovery. The focus of my project is on Adgrg6 (Gpr126), an adhesion class GPCR with known roles in development of the inner ear and myelination of the peripheral nervous system. Mutations in ADGRG6 are known to result in human disease known as Lethal Congenital Contracture Syndrome 9.
The zebrafish embryo can be utilised as an in vivo screening tool to identify small molecules that can modulate the Adgrg6 signalling pathway. The aim of my project is to screen commercially available small molecule libraries to identify compounds that can rescue ear and myelination defects in zebrafish adgrg6 mutants. This phenotype based drug discovery approach is augmented with the use of in vitro cell based assays conducted in partnership with Sosei Heptares during a three month placement. The cell based assays are used to measure wild type and mutant Adgrg6 signalling activity and test hit compounds further with the aim of uncovering compounds that are both potent and specific for the Adgrg6 pathway. These will be useful new tools for the developmental biologist, and may have potential as lead compounds for the design of new therapeutic drugs.
During my project, I have enhanced my insight on multiple drug discovery approaches adopted by academia and industry, along with gaining day-to-day experience of working in an industry lab setting. Moreover, the accessibility of various experienced individuals within pharmacology, cell biology and/or zebrafish has also aided the efficient progression of my research project.
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