Ribosomes imaged on the surface of mitochondria by cryo-EM. Read more.
Calcium influences α-synuclein, a protein implicated in Parkinson's disease. Read more.
Biochemistry, Chemical Biology and Structural Biology
Our research focus
The Biochemistry, Chemical Biology & Structural Biology theme investigates life at the molecular level. We work at multiple levels of complexity that underpin cellular and organismal biology: from the synthesis of bespoke biologically active chemicals, to the dynamics and activity of individual proteins, to the assemblies of the large protein-protein and protein-nucleic acid complexes. Our work is applied to critical real-world problems including synthetic biology, microbial infections, animal development and antibody based diagnostics.
We are experts in a broad range of methods, including synthetic chemistry, enzymology, protein biochemistry, electron cryo-microscopy and X-ray crystallography, high precision mass spectrometry, molecular biology, and high-throughput biology. Our work is being translated through extensive public engagement, spin-out companies, industrial partners, and the Exeter BioEconomy building.
Recent research highlights
Exploiting algae and yeast for synthetic biology
Two separate studies have made significant advances in the field of synthetic biology, developing the tools & methods required to synthesize useful products using biological systems.
Research conducted by Mike Allen in collaboration with industry partner Algenuity has utilised synthetic biology methods using microalgae to make plant triterpenoids in a sustainable way at pilot industrial scale. Triterpenes play a major role in plant defence mechanisms and have shown promise as potential pharmaceuticals for treating HIV and cancer.
Meanwhile, Steve Aves, John Love and collaborators have explored synthetic biology applications using yeast. For yeast to efficiently synthesise useful products, carbon flux must be diverted away from alcohol. The research applied a multifactorial approach to investigate metabolic flux in a library of yeast mutants lacking combinations of alcohol dehydrogenase isozymes. They show that complex gene/environment interactions can be studied and modelled, making this method suitable for understanding and optimising metabolic pathways in other micro-organisms.
Calcium may play a role in the development of Parkinson's disease
The protein alpha-synuclein is strongly implicated in Parkinson’s disease. Jonathan Phillips and a team of international collaborators have shown that alpha-synuclein directly binds to calcium and subsequently relocates within the neuron. This is the first time we’ve seen that calcium influences the way this molecule behaves, a phenomenon that may be important for its (currently undefined) natural function and perhaps also in how it influences Parkinson's disease.
Structural and mechanistic insight into targeting of a bacterial effector
The intracellular pathogen Legionella pneumophila encodes RidL to hijack the host scaffold protein VPS29, a component of retromer and retriever complexes that are critical for endosomal cargo recycling. An international research collaboration including Michail Isupov has solved the crystal structure of RidL in complex with the human VPS29-VPS35 retromer subcomplex, providing structural and mechanistic evidence into how RidL is targeted to endosomal membranes.
Breakthrough in understanding mitochondria
A study led by Vicki Gold has used cutting-edge electron cryo-microscopy to transform our understanding of mitochondria. In particular, the studies give unique insights into the spatial organization of cytosolic ribosomes on mitochondria, supporting the theory that nuclear‐encoded mitochondrial proteins can be synthesized locally at the mitochondrial outer membrane.