Serena Maria Arghittu from the group of FIAS Senior Fellow Roberto Covino successfully defended her PhD thesis in March. In her thesis - Self-regulatory Mechanisms of Proteins at the Cell Surface - she investigated how proteins at the cell surface autonomously adapt to their local environment, a fundamental question in cell biology with implications for how cells achieve signalling robustness and precision in complex surroundings.

Combining molecular dynamics simulations, coarse-grained modelling, and deep-learning approaches, Arghittu explored how glycosylation, membrane composition, and molecular cooperation shape protein behaviour across scales. Her work connected detailed molecular mechanisms to a broader view of the plasma membrane as an active regulatory matrix rather than a passive boundary.    

A central focus of the thesis was the human MET receptor, a key regulator of cellular growth and motility. Through atomistic simulations, Arghittu showed that N-glycans are not merely decorative surface modifications, but active structural regulators. They form transient inter-domain bridges, restrict conformational flexibility, stabilize ligand-binding competent states, and help prevent spurious interactions. Her findings further suggest that glycan interactions can couple receptor conformation to membrane organization, revealing glycosylation as an intrinsic layer of regulation at the cell surface.  

Beyond MET, her thesis also examined adaptive mechanisms in minimal cells through the lipid transporter P116 and introduced TomoSBI, a simulation-based inference framework for cryo-electron tomography. Together, these studies point to a unifying principle: biological systems achieve resilience through self-contained adaptive mechanisms that allow them to respond to their environment with both specificity and flexibility.   

Arghittu’s work thus offers a dynamic view of the cell surface — not simply as the site where signals arrive, but as an active and self-regulating interface that helps determine how those signals are received and interpreted.