I graduated from Sheffield Hallam University in 2021 with a First class grade in Biomedical Sciences. During my studies I particularly enjoyed my subjects around molecular biology and bioinformatics modules. During my studies I managed to gain a placement year in molecular oncology at the Medical School in the University of Sheffield, where I studied as part of the Oncology and Metabolism Department. I worked in using small molecule inhibitors to increase the effects of radiation on lung cancer cells and deciphering the mechanism of action of this. During my final year of study I managed to complete a research project as part of my degree. This project revolved around the effects of mutations on eukaryotic initiation factor 2B (eIF2B) in the context of Vanishing White Matter disease, where I studied the delta protein subunit. My project look at establishing a genotypic-phenotypic relationship between the mutations and clinical presentations of vanishing white matter disease. This was an entirely computational based project and worked to improve my computational skills.
Following my graduation I applied for a PhD position at the University of Nottingham. I managed to secure a position in the School of Pharmacy on a project surrounding mRNA therapeutics and using computational simulation to look at mRNA dynamics in nanoparticles. This has involved me verifying a new mRNA molecular model, and improve this model for more general use as well as develop coarse-grained polymer models.
RNA therapeutics by design - optimising mRNA structures by advanced computation to improve therapeutics and vaccine formulations
Messenger RNAs (mRNAs) are long single-stranded RNAs that can span up to thousands of nucleotides. Recently, cryo-electron microscopy and chemical probing experiments have shown that mRNAs may adopt various structures in vitro and in vivo. Although the details of these structures are still elusive due to their flexibility and heterogeneity, it has been suggested that some regions of mRNAs, such as untranslated regions, form specific structures to regulate protein translation. Further elucidation of such regulatory mechanisms requires understanding of the structures. In addition, mRNAs have a great potential for therapeutic application, as evidenced by the success of COVID-19 mRNA vaccines. However, it is rather surprising that almost nothing is known about the structure of mRNA in these formulations; a better understanding of the structure of mRNA in lipid nanoparticles and polymer-based delivery systems is essential for the further application of mRNA therapeutics.
This PhD project aims to establish a molecular simulation model suitable for long single-stranded RNA to reveal structural ensembles of mRNAs. With support from the experienced and multidisciplinary supervisory team, the successful candidate will develop a novel computational approach for mRNA structures based on existing coarse-grained molecular models. After validating the model with bioinformatics and experimental data, we will further investigate mRNA structures under conditions of polymer-based vaccine formulations. We will seek better strategies to design RNA therapeutics in silico.