Our Research
The cell membrane is a dynamic interface that controls material exchange, signalling and cellular responses. Its complex and asymmetric composition is actively organised by the cytoskeleton, lipid transporters, membrane contact sites and trafficking pathways. We study how local changes in membrane composition and shape influence receptors, signalling and cell behaviour. We also investigate how cells generate specialised membrane domains that lead to non-clathrin and dynamin-independent endocytosis that in turn participates in the regulation of membrane tension. Our work combines new membrane probes, high-resolution microscopy, protein conformational analysis and in vitro reconstitution with tools that measure membrane biophysical properties, such as lipid packing and tension. Working across diverse model systems and disciplines, we aim to understand the cell membrane as an active living material.
Themes
Membrane Composition- Leaflet by Leaflet
The plasma membrane is a chemically diverse, asymmetric and highly organised interface rather than a uniform two-dimensional fluid. We study how lipid composition and asymmetry, membrane proteins and the underlying cortical cytoskeleton work together to generate this organisation across multiple length and time scales. A particular focus is how interactions between the two leaflets of the bilayer allow information and organisation to be transmitted across the membrane. We are interested in how nanoscale domains are formed, maintained and remodelled by active cellular processes, and how changes in lipid composition or cytoskeletal activity alter membrane organisation. Through these studies, we aim to understand the physical principles that allow the plasma membrane to remain both asymmetrically structured in biophysical properties and composition and yet highly dynamic.
Signalling & Mechanobiology
The cell surface is where cells encounter and interpret both chemical and mechanical information from their environment. We investigate how membrane organisation, receptor clustering, adhesion and the cytoskeleton are integrated to regulate cellular signalling. Our work spans signalling systems including GPCRs, insulin receptor signalling and cadherin-mediated adhesion, asking how the spatial organisation and dynamics of receptors and adhesion molecules at the plasma membrane shape downstream responses. In parallel, we study how mechanical cues such as substrate properties, cell–cell adhesion and cytoskeletal forces influence membrane organisation and signalling. A particular focus is the interplay between integrins, cadherins, actomyosin and membrane components, and how force-dependent changes at the cell surface feed back onto biochemical pathways. Together, these studies aim to understand how cells integrate chemical and mechanical inputs into coordinated cellular responses.
Regulation of Endocytosis
The plasma membrane is continuously remodelled as cells internalise, recycle and redistribute material from their surface. We study the molecular mechanisms and physiological roles of non-canonical endocytic pathways, with particular emphasis on the CLIC/GEEC pathway of clathrin- and dynamin-independent endocytosis. A major focus is how these pathways regulate membrane tension, surface area and composition as cells change shape, move and respond to their environment. We investigate how cargo is selected and organised before uptake, how the cytoskeleton drives membrane deformation and internalisation, and how membrane tension feeds back onto endocytic activity. Alongside understanding the basic biology of CLIC/GEEC endocytosis, we are also exploring its pharmacological modulation. By identifying molecular regulators and small-molecule perturbations of this pathway, we aim to connect fundamental mechanisms of membrane trafficking with possible therapeutic applications. More broadly, our work seeks to understand how trafficking, mechanics and signalling are integrated.
Reconstituted Systems
The complexity of living cells can make it difficult to identify which molecular interactions are sufficient to generate a particular behaviour. We therefore complement our cellular studies with reconstituted and in vitro systems built from defined components. Using model membranes, purified proteins and cytoskeletal systems, we reconstruct selected aspects of plasma membrane organisation and dynamics in a controlled setting. These experiments allow us to directly test how lipids, membrane proteins, actin and molecular motors interact, and to separate passive physical interactions from energy-dependent processes. By moving iteratively between minimal systems and living cells, we aim to identify the fundamental mechanisms that give rise to the organisation, dynamics and emergent properties of the cell surface.