Giulia Bigotti’s main interest is spontaneous and assisted protein folding, and in the past years as a Wellcome Trust fellow in the School of Biochemistry she has been focusing on type II chaperonins, a specific class of molecular chaperones that aid protein folding in the cytoplasm of archaebacterial and  eukaryotic cells. These large multi-subunit complexes provide a protected environment for non-native proteins to fold, and use energy derived from ATP binding and hydrolysis to drive a series of structural rearrangements that enable them to capture, engulf and then release unfolded polypeptide chains that would otherwise become enmeshed in the crowded cellular milieu. The model system of her studies is the hetero-oligomeric chaperonin form the archaeon Thermosplasma acidophilum, which she expressed recombinantly in E.coli in order to make it more accessible to study. By using a combination of molecular genetics and biochemical/biophysical analysis, recently complemented by a structural approach based on single particle cryoelectron microscopy, she aims at characterising at the molecular level the cycle of highly controlled events leading to correct folding of nascent or misfolded protein substrates. Given the critical involvement of this group of molecular chaperones in severe human pathologies such as cancer, neurodegeneration and specific neuropathies, any advance in this basic knowledge has strong implications also in translational research.

She is also involved in a series of collaborations for the structural and functional characterization of dystoglycan, a highly glycosylated protein complex that links the cytoskeleton with the extracellular matrix, mediating crucial physiological functions such as mechanical stability of tissues, matrix organization and cell polarity. Hypoglycosylation of its extracellular component weakens this link. resulting in severe neuromuscular pathological states (secondary dystroglycanopathies), and her current research aims at understanding the molecular bases of such hypoglycosylation.