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. We also examine how N-terminal acetylation of Grh1 modulates biomolecular condensation, oligomerisation, and liquid–solid transitions. 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.

A recent breakthrough in biology was the discovery that membrane-less organelles, or biomolecular condensates, form within cells through a process known as phase separation (PS). These compartments, composed of proteins and RNAs, provide dynamic microenvironments without the need for surrounding membranes. Examples include processing bodies, stress granules, germ P granules, nucleoli, Cajal bodies, and PML bodies. Although Flory and Huggins established the thermodynamic principles of liquid-liquid phase separation in the 1940s, its role in cell biology was only recognised in 2009, when P granules in worm embryos were identified as liquid-like condensates. Since then, PS has emerged as a central organising principle in both healthy physiology and disease. 

In our group, PS is studied as a key mechanism in the organisation of secretory organelles, unconventional secretion under stress, and the pathogenesis of neurodegenerative disorders. A major focus is the protein Annexin A11 (ANXA11), a calcium-dependent phospholipid-binding protein with a long intrinsically disordered N-terminal region. ANXA11 is implicated in cancer, autoimmune diseases, and neurodegeneration, and mutations in its disordered domains are directly linked to amyotrophic lateral sclerosis (ALS) and multisystem proteinopathies. These mutations alter its ability to undergo PS and to regulate stress granule dynamics, often triggering aberrant liquid-to-solid transitions. Beyond ANXA11, we investigate the interplay of FUS and TDP-43, central components of stress granules whose condensation properties are finely tuned in healthy cells but prone to pathological aggregation in ALS and frontotemporal dementia (FTLD). By combining recombinant protein biophysics and advanced imaging, we aim to elucidate how pathogenic variants impact the co-condensation, stability, and maturation of these assemblies. 

Together, these projects explore how intrinsically disordered proteins form, regulate, and sometimes misregulate condensates. By uncovering the physical rules that govern their assembly, we seek to understand how condensates contribute to cellular organisation, and how their dysfunction drives neurodegeneration and other diseases.