The Golgi complex, with its distinctive stack of flattened cisternae, is one of the most recognisable organelles in eukaryotic cells. Its “pancake-like” morphology enhances vesicle tethering, trafficking efficiency, and processing capacity, yet the molecular determinants of this unique architecture remain poorly understood. The high elasticity of the organelle, which allows it to fragment and reassemble during mitosis, further underscores its dynamic nature and the need for precise structural regulation. Central to this organisation are the Golgi matrix proteins (GMPs), primarily the Golgins and GRASPs. Both families are enriched in intrinsic disorder and multivalent interaction motifs, features increasingly associated with biomolecular condensation. Golgins form extended coiled-coil structures that capture vesicles and tether cisternae, while GRASPs, anchored to membranes via post-translational modifications, mediate golgin-arrestment and Golgi ribbon formation. Together, they provide the scaffold that sustains Golgi integrity, positioning, and dynamics. 

In our group, we investigate how GMPs collectively regulate Golgi structure and function, utilising complementary models across species. In yeast, we investigate the Bug1–Grh1 complex as a minimal ancestral system to probe supramolecular assembly, condensate formation, and membrane anchoring. In higher eukaryotes, we study Golgin-45-GRASP55, a medial–trans complex essential for ribbon formation and control of membrane curvature. In parallel, we investigate TMED/p24 transmembrane proteins, partners of GRASPs, which may act as cargo receptors and unconventional secretion channels, linking matrix proteins to membrane remodelling.

By integrating spectroscopy, calorimetry, high-resolution microscopy, and cryo-EM, we aim to decipher how GMPs generate the Golgi’s characteristic morphology. These studies not only test the hypothesis of a “liquid-crystalline Golgi”, where condensates shape membranous spaces, but also provide insight into how disruption of these structural proteins might contribute to cancer development (where Golgi fragmentation is commonly observed) and secretion-related disorders.

Biomolecular condensates provide cells with a dynamic mechanism to organise molecules and biochemical reactions without the need for a surrounding membrane. Their formation is frequently driven by multivalent and transient interactions involving intrinsically disordered regions, making them highly responsive to changes in the cellular environment. A major focus of our research is Annexin A11 (ANXA11), an unusual protein that connects two forms of cellular compartmentalisation: membrane-less RNA granules and membrane-bound organelles. Its intrinsically disordered N-terminal region promotes condensation, whereas its C-terminal annexin domains mediate membrane interactions. Through these properties, ANXA11 acts as a molecular tether between RNA granules and lysosomes, enabling long-distance RNA transport in neurons. This system provides a powerful model for understanding how protein disorder, phase behaviour and membrane interactions cooperate to generate cellular function, and how subtle changes in these properties can lead to dysfunction. ALS-associated variants of ANXA11 can alter condensate dynamics, assembly and RNA-granule transport, linking aberrant phase behaviour to neurodegeneration. We are also interested in the broader relationship between condensates and ALS-associated proteins such as FUS and TDP-43. Rather than considering pathological aggregation simply as the solidification of a liquid droplet, emerging evidence points to a more complex landscape in which RNA interactions, local concentration, stress and changes in condensate organisation can redirect proteins toward distinct functional or pathological states. Our goal is to understand the molecular mechanisms that determine when condensation is functional, how its physical properties are regulated, and what drives a dynamic assembly toward dysfunction or irreversible aggregation.