Funding
Our research is made possible by funding from:
Living systems are highly dynamic, continuously reshaping and reorganising as their molecular components associate and dissociate. Rather than relying on deterministic genetic programmes, molecular interactions can respond to environmental changes and maintain robust cell responses. Our research aims to reverse-engineer molecular assemblies to understand how they function. We mainly rebuild transient molecular interactions at the cellular interface, and also explore how other cells recognise such controlled mimetic interfaces.
Although inherently reductionist, the bottom-up reconstitution approach is uniquely positioned to dissect the complexity of these interactions and bridge the gap between molecular and cell-level organisation. Our primary focus is on reconstructing glycan–protein assemblies associated with lipid membranes, which we characterise using a range of surface-sensitive techniques. Whenever possible, we perform “biochemistry under the microscope,” directly observing and quantifying dynamic interactions by single-molecule tracking (video on the right).
Peptidoglycan synthesis
While enzymes involved in peptidoglycan synthesis are popular targets for antibiotics, their activity largely depends on the cellular context and is regulated by various molecular factors. We rebuild molecular networks that control peptidoglycan synthesis during bacterial division. By accounting for relevant boundary conditions, such as confinement to cellular membranes and the presence of peptidoglycan or FtsZ cytoskeleton, we can quantify the dynamics of the interactions with precision that remains difficult to achieve in a living cell. Our reconstitution assays can also be adapted as a high-throughput screening platform for target-based discovery of novel peptidoglycan synthesis inhibitors.
Bacteria-host communication
The biofilm matrix, where glycans represent one of the primary structural components, serves as a communication medium between bacterial cells and other species. While the chemical means of communication, such as quorum sensing, have received decades of attention, how bacteria react to the change in composition and mechanical remodelling of their own matrix or the matrix produced by another organism is far less understood. We aim to rebuild biofilm matrix components on a planar surface to investigate molecular interactions and monitor their recognition by bacterial cells or host immune cells at high spatio-temporal resolution. Another objective is to investigate how the host tissue environment affects bacterial pathogenesis and biofilm formation.
Dynamics of glycocalyx
Bulky glycocalyx components are osmotically active space fillers that define the thickness and viscoelastic properties of the cell interface. However, the relation between their ensemble architecture, dynamic re-organisation and cell functions remains largely unexplored for most cells. Here, we focus on developing novel approaches to probe the physical properties of the glycocalyx in synthetic assembly and correlate them with the glycocalyx assembly present on a living cell.
