Research Fellows Directory
Dr Justin Benesch
University of Oxford
To understand protein function we need to not only understand protein structure, but also to focus on their dynamic aspects. This includes their synthesis, folding into functional or pathogenic forms, interactions with other cellular components, and degradation. After their synthesis, the folding of many protein chains into the correct functional arrangements often requires assistance by members of the molecular chaperones. These species also have a vital role to play during conditions where the cell is stressed, by preserving and subsequently repairing damaged proteins. The mechanism by which they carry out these housekeeping duties is not fully understood, yet malfunctioning of this system results in a variety of diseases and even premature death. In our current research we are focussing on the least well understood family of the molecular chaperones, the small heat-shock proteins (sHSPs). In addition to their chaperone function, members of these proteins have been implicated in various diseases including cataract, motor neuropathy, and Alzheimer’s. We are examining how these proteins behave and interact with substrates under stress conditions, and how they fit into the overall chaperone network in the cell. We have shown the sHSPs to be very dynamic which, coupled to their large size, has hampered conventional approaches to their study. However, as we are concurrently developing and employing mass spectrometry strategies for the study of these proteins, it is our goal to monitor their reactions in real time, and moreover, in conditions which closely mimic the cell. In this was we are delineating the reaction network, associated kinetics, and structural characterisation of the sHSPs chaperone system. This will open the door for us to examine the effect of variants of these proteins and their substrates on the global chaperone network, thereby gaining novel insight into the pathologies of the associated disease states.
Interests and expertise (Subject groups)