Protein self-assembly phenomena
My research interests focus on the behaviour of proteins: the molecules that are responsible for the vast majority of functions in living organisms. The controlled self-assembly of proteins into well-defined structures and functional assemblies is essential to our well-being, however occasionally protein self-assembly takes place inappropriately. When this happens in the body it typically causes disease, and familial diseases as well as diseases of ageing (such as Alzheimer's Disease, Parkinson's Disease, cataract and type II diabetes) are all recognised to be the result of improper protein self-assembly. Protein self-assembly can also cause havoc in industrial processes including the production of biopharmaceuticals (e.g. insulin). When this occurs, the pharmaceutical is often lost as an irretrievably tangled mass of gelled protein. All is not lost, however: the self-assembly of proteins also underpins the texture of foodstuffs including egg, meat and milk products. It is understanding this process of self-assembly - to prevent or reverse disease, or to drive the development of new materials and foodstuffs - that forms one focus of my research efforts.
Through collaboration with Dr Nicola Stanley-Wall, a molecular microbiologist at the University of Dundee, we have recently investigated the structure and function of an unusual interfacially-activated protein called BslA. BslA partitions to an air/water or oil/water interface, where it undergoes a controlled, environmentally-responsive structural transformation. In Bacillus subtilis biofilms, this structural transformation results in a water-repellent coat that protects the bacteria from environmental insult. Two papers have appeared in PNAS (See publications ) and this animation illustrates how it works.
A lot of my research is industry focussed. I am part of the management committee of the Edinburgh Complex Fluids Partnership whose aim is to advance and innovate formulation and complex fluid design and processes.
A more recent and growing research interest of mine is in proteins that have no well-defined structure, the so-called 'intrinsically disordered proteins', which share many of the physical characteristics of polymers and colloids, i.e. traditional soft matter. This class of proteins is an enigma: according to traditional views of biomolecular science they should not exist, and where they do they should be rapidly destroyed by gatekeeper mechanisms. Instead, they appear to be surprisingly common and responsible for a range of essential cellular functions. Existing biophysical tools are geared towards crystalline and folded proteins; the emerging importance of intrinsically unfolded proteins offers an exciting opportunity for soft matter physicists to have substantial and lasting impact on biomolecular science. We use solid-state and solution NMR techniques, spectroscopic analysis, mass spectrometry, rheology, optical tweezers, AFM and electron microscopy to investigate self-assembly mechanisms.