Dr Joel Loveridge
I am interested in the relationship between the structure, dynamics and function of enzymes, as a route to understanding and controlling nature’s chemistry. This work involves multidimensional NMR spectroscopy in conjunction with other biophysical techniques. Cardiff’s flagship 600 MHz Bruker NMR spectrometer is equipped with a quadruple resonance QCI cryoprobe capable of simultaneous pulsing and decoupling on 1H, 13C, 15N and 31P, making it ideal for studies of proteins, nucleic acids and their complexes, as well as small molecules. The ability to switch the 1H channel to 19F further extends its utility to include fluorine-labelled biomolecules or xenobiotics. Current projects include:
Dihydrofolate reductase and the physical basis of enzyme catalysis
In collaboration with Prof. Rudolf Allemann, this work studies the effects of organic cosolvents on the structure and dynamics of the model enzyme dihydrofolate reductase, and investigates the dynamics of the bound ligands. By relating these results to kinetic data, we hope to distinguish between models in which protein motions are coupled to those of the bound ligands in a manner which directly affects the rate constants of the reaction and models in which conformational effects are important for setting the correct environment for reaction but which play an otherwise passive role the chemistry itself.
Binding of metal-based drugs to biomacromolecules
In collaboration with colleagues in the School of Chemistry, this work seeks to characterise the interactions of metal-based drug candidates with targets such as amyloid-beta peptides (the causative agents of Alzheimer’s Disease) and DNA. A range of biophysical techniques, including multidimensional NMR spectroscopy, are used to probe these interactions.
NMR pulse sequence development
This work seeks to develop new NMR pulse sequences for investigating biomolecular interactions. This mostly focuses on interactions between proteins and phosphorus-containing molecules such as nucleotides, cofactors, drugs and phospholipids.
The bulgecins are a group of sulfonated glycopeptides produced by certain bacterial species, which increase the effectiveness of beta-lactam antibiotics. This work uses a range of genetic, biochemical, spectroscopic and microbiological methods to study the biosynthesis and activity of the bulgecins. The antibiotic resistance of one of the producing organisms is also of interest.
Expressions of interest in any of these projects from prospective PhD students are always welcome.