We combine different approaches to study the molecular structure of isolated proteins, protein aggregates, supramolecular complexes and cell membranes.
Our expertise in this area includes molecular biology, biochemical/biophysical techniques, spectroscopy, structural biology and computational methods.
These multidisciplinary studies allow our intervention in many fields of life sciences, unravelling the molecular bases of biological processes and human pathologies, with innovative implications in drug discovery and delivery.
Structure and dynamics of proteins.
We produce and characterize recombinant proteins, both in the wild type and mutant pathogenic forms, to study the molecular details at the base of their function and role in biological processes. In particular we focus on:
Biochemical and biophysical properties, as flexibility and stability against chemicals, temperature and pressure or other behaviours in solution.
Structure at atomic level by x-ray diffraction, small angle x-ray scattering and cryo-electron microscopy, as well as different spectroscopic techniques. Besides observation of structural motifs related to function, proteins are set as targets for drug discovery and the study of interactions with molecular partners or ligands (i.e. candidate drugs).
Molecular simulation in silico, to support experimental hypotheses, answer to pathologies-related questions and propose new therapeutic strategies for in vitro tests.
Among the different projects in this areas, we can mention the research of antiviral compounds, Raman spectroscopy and oncological diagnosis, molecular physiopathology of rare genetic diseases (AGel amyloidosis, methylmalonic acidemia with cblC-type homocystinuria) and anti-tumoral therapy
Structure and dynamics of cell membranes
The study of lipid systems is of great interest both in itself, being complex physical systems, and for the prospective of addressing specific issues of biophysical interest through the construction of appropriate models. Last but not least, let’s consider its relevance and involvement in the biotechnology field. In recent years, our studies have focused on investigating some specific interactions between lipid components and the amyloid beta-peptide, present as main component in the amyloid plaques, distinctive hallmark of the Alzheimer’s disease.
Extracellular vesicles (EVs) are nanometer-sized particles “made by cells for cells” to shuttle lipids, proteins and nucleic acids. As potent signal transducers and intercellular and inter-organismal communicators, EVs mediate physiological processes and help to spread various diseases, including cancer and infections. Also, their bioavailability and stability, along with their mild toxicity and immunogenicity, make them exploitable as nano-delivery systems with targeted cellular uptake. EV exploitation as biomarkers for “liquid biopsy”, the creation of bioactive or vaccines based on EVs, along with further clinics and technology transfer studies, make EVs a turning point for the development of nanotechnology in biomedicine and beyond (nutraceutics, cosmetics, etc.).
Supramolecular complexes represent the highest levels of complexity in this area and consist in the study of macromolecules that non-covalently assemble to trigger/regulate signalling or other biological processes. Approaches include molecular biology methods, next generation sequencing, surface plasmon resonance, atomic force microscopy and cryo-electron microscopy.
We study the Spinal Muscular Atrophy (SMA), a highly impacting neuromuscular disorder caused by deletions or mutations of the Survival Motor Neuron protein (SMN). SMN plays a role in translation directly interacting with ribosomes. Our major effort is paid on the binding between SMN and ribosomes and the impact of different SMN domains on translational control.
We also investigate the Virus Like Particles (VLPs), which naturally occur during production of viral structural proteins. These particles are not contagious, since they lack the viral genetic material. VLPs are studied to understand the assembly of viral like structures before virus and assess the activity of drug candidates as antivirals.