The chemistry biology interface
Understanding the chemistry of life and the processes of life is central to this theme and plays an important role in drug design and development, as well as sustainable catalysis. Research in this area spans bioinformatics, biophysical characterisation of enzymes, designing and synthesising tools for the interception and/or imaging of pathways, enzyme, metabolic pathway engineering and synthetic biology. Research across EaStCHEM in this area is highly multidisciplinary and applied impacting upon medicine, and the pharmaceutical and agrochemical industries.
Research in this theme has many diverse aspects and facets. One key focus is the exploration of the chemistry of disease (microbial, parasitic, neurological and genetic) and the design and development of biological and chemical tools to interrogate and address disease, including parasitic diseases that disproportionately afflict the health and livelihoods of people in the World’s poorest countries. Proteus, with a focus on imaging and developing treatment for lung disease, is centred within EaStCHEM at the University of Edinburgh, whilst the St Andrews Multidisciplinary Anti-infective Research and Therapeutics (SMART) Centre is housed within the School of Chemistry at St Andrews.
A molecular understanding of protein structure and function is key to the drug discovery process and an underpinning research area is computational chemistry. Molecular dynamics simulations, quantum-mechanical/molecular-mechanical computations and free energy calculations are combined with biophysical assays and X-ray crystal structure data to understand enzyme activity and inhibitor action, and to guide the design of new drug targets These drugs can also be tracked/monitored once inside living cells using powerful, label or label-free spectroscopic techniques, researchers across EaStCHEM play a key role in developing such techniques.
Another and interwoven aspect is the exploration and engineering of enzymes and metabolic pathways. This includes the study of natural product biosynthetic pathways at the informatics, genetic, enzymatic and chemical levels, interrogation of pathogen metabolic pathways, and the generation of novel synthetic biological pathways enabling sustainable production of natural product analogues, high value compounds (advanced pharmaceutical intermediates, APIs) as well as bulk chemicals. Displacement of current synthetic process chemistry with enzymatic chemistry (known as “biocatalysis”) which is greener, more selective and more cost effective is imperative, and research teams across EaStCHEM pursue the discovery understanding and development of novel enzymes. These reactions can happen in vitro with purified enzymes or can carried out in living cells. There is a considerable amount of interaction with industry and biotech nationally and internationally in this area.
At EaStCHEM, our particular research strengths at the Chemistry Biology Interface are in the areas of:
- Chemical biology
- Medicinal chemistry
- Target identification and characterisation
- Natural product and analogue synthesis
- Biorenewable materials
- Synthetic Biology (enzyme engineering, and pathway engineering)
- Biological imaging