Giulia Bigotti is a protein biochemist and biophysicist, whose work centers on understanding how proteins form and work in specific environments. She came to Bristol as a Wellcome Trust fellow in the School of Biochemistry and dedicated most of her research to spontaneous and assisted protein folding, specifically 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. 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 in translational research.

She is also involved in a series of collaborations for the structural and functional characterization of dystoglycan (DG), a highly glycosylated protein complex that links the cytoskeleton with the extracellular matrix (ECM), mediating crucial physiological functions such as mechanical stability of tissues, matrix organization and cell polarity.

In recent years she has been working in the School of Translational Health Sciences (Bristol Medical School) on two main fronts, namely:

- the molecular investigation of one of DG’s interactors, the ECM protein agrin, which is best known for its essential role in the recruitment of acetylcholine receptors at the neuromuscular junction. Her interest lies in investigating the regenerative potential of agrin on heart muscle cells (cardiomyocytes) and its general cardioprotective effect as shown in animal models. Such effects have been proposed to depend on agrin’s interaction with DG, although the chain of events as well as the other factors involved in such mechanism are still poorly characterised. Together with her collaborators in Bristol and in Rome, Giulia is working on the characterization of the agrin-DG axis in human hearts, as well as on producing a miniaturized form of agrin to study in vitro at the molecular level. Besides the fundamental interest in understanding the mechanisms underlying the regenerative activity of agrin, our final aim is to possibly harness and develop its potential as a therapeutic for treating heart damage/failure, which is the leading cause of death in the developed world

- the investigation of the N-terminal domain of α-dystroglycan (α-DGN) as a broad-range antiviral agent against enveloped viruses