The main interest of the group is the study of protein-protein interactions that vehicle the communication between host and microbiota or complement system and pathogenic bacteria, we use a combination of protein and therapeutic molecules production, X-ray diffraction, biochemical and biophysical methods that allow us to study snapshots of the protein complex interactions as well as the dynamic behavior that both underlie the functional outcomes of those interactions.

A greater understanding of the atomic-level communication between host and bacteria (pathogenic or symbiotic) will afford deeper insights into the myriad biological,immunological, and metabolic processes that involve the microbiota (Fernandez et al. 2012; Lopez-Estepa et al.2012). Biomedically relevant examples include the interaction between extracellular matrix proteins and virulence factors and between the complement components and diverse immune evasion proteins.

Fig. 1. 2.6-Å crystal structure of UlaG (Garces et al. 2008, 2010), a novel hexameric Mn²⁺-dependent metallo-beta-lactamase that funnels ascorbate 6-phosphate down the pentose phosphate shunt, therefore underpinning vitamin C assimilation by commensal and enteropathogenic Gram-negative and Gram-positive bacteria (Fernandez et al. 2011).

The human complement system is a collection of soluble and membrane-associated proteins that monitor the blood and tissue interstitial fluids for pathogens, apoptotic cells and immune complexes. In addition to its prominent role in innate immunity, complement also modulates the adaptive immune system. Pathogens have evolved sophisticated molecular weaponry that allows them to escape surveillance from the complement system, a strategy designated immunoevasion. In the COMPLEMENTO Consortium we are focused in elucidating the structures and mechanistic details of the complement system components (Alcorlo et al.2011) and their protein complexes with virulence factors with immunoevasive properties

 We are interested in the development and improvement of new technologies and production tools for complex protein biologics using yeast expression methodologies. With this interest, the group is a member of the FP7 Project ComplexINC that comprises academic and industrial partners from all over Europe. 

 ComplexINC conceptualizes and systematically generates advanced toolkits to enable high-throughput assembly of complex biologics and metabolic pathways using eukaryotic expression systems. The ultimate goal of these toolkits, including two yeast-based toolkits developed in our laboratory, is enabling micro- and large-scale production of high-quality protein biologics for drug discovery and as biotherapeutics.