MSci (Bristol), PhD (Edin)
John Henry Coates Fellow; 1851 Royal Commission Research Fellow
After spending the vast majority of my youth in Maidenhead, Berkshire, and attending my local comprehensive, I began my path in research as an undergraduate in Chemistry at the University of Bristol. During my time at Bristol I quickly became captivated by chemical reaction mechanisms – that seemingly simple chemical transformations are often nothing of the sort – and I’ve been chasing them ever since.
Following a crack at using computational chemistry (Prof. Neil Allan, Dr Natalie Fey) and ultrafast lasers (Prof. Andrew Orr-Ewing FRS) to probe reaction mechanisms during my time at Bristol, I next travelled north, to Edinburgh, to undertake doctoral research in the laboratory of Prof. Guy Lloyd-Jones FRS. Supported by an iCASE award from the EPSRC and Syngenta, here I encountered reactions that were, forgivingly, a little slower than a billionth of a second – but by no means any less multifaceted. Reaction monitoring and kinetic analysis – watching chemical processes evolve in real time, and analysing them quantitatively – were the order of the day in Edinburgh, but I also learned a great deal about NMR spectroscopy, the gift of fluorine, heavy atom isotope effects, computational organic chemistry, and fundamental aspects of catalysis.
In 2022 I was awarded a Research Fellowship from the Royal Commission for the Exhibition of 1851 to bring my experience as a mechanistic organic chemist to bear on a new challenge: understanding the prebiotic origins of coded peptide biosynthesis. I now work in the Protein and Nucleic Acid Chemistry Division at the MRC Laboratory of Molecular Biology under the mentorship of Prof. John Sutherland FRS, and hold the non-stipendiary John Henry Coates Research Fellowship at Emmanuel College.
Chemistry (Part IA)
The coded biosynthesis of proteins – the translation of genetic information into function – is a defining pillar of molecular biology, and a prerequisite for life.
In no small part due to prodigious research undertaken at the LMB itself, the mechanism of translation in extant biology – life in its current form – is known in exquisite atomistic detail, unimaginable to the pioneers of nascent molecular biology. We know how it works, where it happens, and how to manipulate it. We know the underlying genetic code that governs translation, and we know that curiously formed complexes of RNA – tRNAs – are responsible for delivering the right amino acid, at the right time, during protein biosynthesis. Yet the picture is incomplete, and fundamental pieces are missing. One profound dichotomy is that extant translation depends vitally on an ensemble of proteins, yet these very proteins could not have emerged before a means to generate them. The genetic code is essentially universal amongst cellular life forms, and yet myriad alternative codes could feasibly perform the same role. How did our genetic code emerge, why should it be the way it is, and how did specific sequences of nucleotides (codons) get assigned to specific amino acids, before “biology” even existed?
In collaboration with a multidisciplinary team in the Sutherland group, I seek to tackle these questions by studying truncated mimics of extant tRNAs from the perspective of a mechanistic chemist - how they might acquire - and lose - certain amino acids selectively, and how amino acids might be transferred efficiently from one tRNA to another, all without the aid of the colossal biomolecular machinery that underpins life as we know it.