Structure and dynamics of molecular interactions using NMR spectroscopy
Chris' research develops and applies solution NMR spectroscopy to study the dynamics and interactions of biomolecules, ligands and drug molecules, and supramolecular systems.
Approximately one third of eukaryotic proteins are translocated co-translationally into the endoplasmic reticulum for processing prior to secretion. Within the ER, N-linked glycosylation of the nascent polypeptide defines a ‘glycan code’ that regulates its engagement with components of the glycan quality control (GQC) pathway. Failure of GQC can result in protein misfolding, accumulation in the ER, and the onset of disease. Within the Waudby group, we are developing strategies to study the misfolding of glycoproteins using multinuclear, ex vivo NMR, coupled with single molecular biophysical methods, to study the structural basis of recognition of misfolded glycoproteins by components of the GQC pathway.
The group also continues to push the capabilities of NMR spectroscopy with the development of new experiments and software for the analysis of biomolecular dynamics. We are developing improved acquisition schemes and easy-to-use analysis methods, including the popular software package NMR TITAN, to extract the fullest possible information from experimental measurements.
Selected publications
High-resolution ex vivo NMR spectroscopy of human Z ɑ1-antitrypsin.
Jagger AM, Waudby CA, Irving JA, Christodoulou J, Lomas DA.
Nat Commun (2020) 11 6371.
https://www.nature.com/articles/s41467-020-20147-7.pdf
Interactions between nascent proteins and the ribosome surface inhibit co-translational folding.
Cassaignau AME, Włodarski T, Chan SHS, Woodburn LF, Bukvin IV, Streit JO, Cabrita LD, Waudby CA, Christodoulou J.
Nature Chemistry (2021) 13 1214-1220.
https://www.nature.com/articles/s41557-021-00796-x.pdf
Analysis of conformational exchange processes using methyl-TROSY-based Hahn echo measurements of quadruple-quantum relaxation.
Waudby CA, Christodoulou J.
Magn Reson (2021) 2 777-793.
https://mr.copernicus.org/articles/2/777/2021/mr-2-777-2021.pdf
Two-Dimensional NMR Lineshape Analysis.
Waudby CA, Ramos A, Cabrita LD, Christodoulou J.
Sci Rep (2016) 6 24826.
https://www.nature.com/articles/srep24826.pdf