Speaker
Description
Understanding biological systems at the molecular and mesoscopic scale requires the combined power of advanced experimental techniques and computational modelling. A special example is the G-quadruplex (G4) DNA structure formed at human telomeres, which is a promising target for antitumoral drug design. A combined experimental and computational approach has been used to investigate the conformational changes in multimeric human telomeric G4s induced by small-molecule ligands, focusing on how inter-unit stacking geometry and thermal stability are modulated by ligand binding. Small-angle X-ray scattering (SAXS) provides low-resolution structural envelopes of the multimeric assemblies in solution, circular dichroism (CD) reports on topology and thermal unfolding, and coarse-grained molecular simulations offer dynamic insight into the conformational landscape at timescales inaccessible to atomistic approaches. Together, these techniques paint a coherent picture of how ligands reshape G4 multimerisation, with implications for the rational design of telomere-targeting therapeutics.
Three further research lines will be also outlined, in which we apply physical methods to biological questions: the study of proteome dynamics near cell death in extremophilic bacteria via neutron scattering and multiscale molecular dynamics; the structural characterisation of lipid membranes by neutron reflectometry and its connection to cell membrane behaviour; and the multimodal analysis of bioinspired materials through digital microscopy, FTIR, and Raman spectroscopy. All of these lines are supported by the in-house development of dedicated neutron spectroscopy instrumentation, which enables access to length and time scales of direct biological relevance.