Harden M. McConnell Lecture
About the Lecture
While cryo-EM has transformed our view of the structures of protein assemblies, behind the scenes gas phase structural biology has been emerging. Over a number of decades mass spectrometrists have revealed that the folding and topology of protein complexes can be retained in the gas phase, if appropriate experimental parameters are applied. These discoveries led to early compelling studies of antibody-antigen complexes, viruses, ribosomes and molecular chaperones. More recently ‘snapshots' of membrane protein complexes in the gas phase have been particularly enlightening. Widely considered the most challenging of protein complexes, but yet the most important given their physiological roles, the gas phase turns out to be an excellent medium in which to interrogate hydrophobic membrane proteins. When encased in detergent micelles, or other membrane mimetics, the effects of lipids on stability, conformational change, dynamics and protein interactions are revealed. As such, mass spectrometry is informing membrane embedded efflux pumps (often implicated in antibiotic resistance mechanisms) assembly of membrane protein interfaces (primarily in solute carriers) and receptor mediated signalling pathways (typically of GPCRs). In this lecture I will trace the history of these developments using selected highlights to illustrate progress made to date. Finally, I will describe exciting future developments - soon to be realised…..
About the Speaker
Carol holds the Oxford Chair of Dr. Lee's Professor of Chemistry and is the first Director of the Kavli Institute for Nanoscience Discovery at the University of Oxford. She is recognised for using mass spectrometry to further research into the 3D structure of proteins and their complexes.
During her early research Carol developed and applied mass spectrometry to show how protein folding could be monitored in the presence of molecular chaperones. This research prompted her to find new ways to preserve mega Dalton complexes in the gas phase and led her to uncover the heterogeneity and dynamics of numerous multi protein complexes. In recent work she demonstrated the numerous roles played by lipids in regulating the structure and function of membrane protein assemblies. Her current interest is in uncovering the synergy of lipid and drug binding. With this information she is exploring new ways to characterise receptor-signalling complexes.
Carol's graduate education was completed whilst working full-time in industry. She was subsequently admitted to the University of Cambridge where she completed her PhD in two years. Following an eight-year career break to begin raising her three children, she returned to research at Oxford. In 2001 she became the first female Professor of Chemistry at the University of Cambridge, returning to Oxford in 2009 to take up the Chair of Dr. Lee's Professor of Chemistry.
Her research has attracted numerous international awards and distinctions. Her most recent awards are: The 2022 Benjamin Franklin Medal in Chemistry, The 2022 Louis Jeantet Prize for Medicine, The European Chemistry Gold Medal from the European Chemistry Society (EuChemS), The Othmer Gold Medal from the Science History Institute, The Academy Prize from the Royal Academy of Belgium and The Royal Medal A from the Royal Society. Her distinctions include International Honorary Member of the American Academy of Arts and Sciences (2021), Foreign Associate of the US National Academy of Sciences (2017), Dame Commander of the Order of the British Empire (DBE) in 2013 for her contributions to Science and Industry and she is also a former President of the UK Royal Society of Chemistry.
Faculty Host: Jesse L. Beauchamp, Mary and Charles Ferkel Professor of Chemistry