Structural and Physical Determinants of Complex Virus Assembly
RESEARCH GROUPS

Carmen San Martín
Group Leader
Research Summary
We are interested in the structural and physical principles that govern assembly and stabilisation of complex viruses. As a model system we use adenovirus, a challenging specimen of interest both in basic virology and in nanobiomedicine. We are also interested in assembly of complex marine viruses structurally related to adenovirus. We approach the problem from an interdisciplinary point of view, combining biophysics, computational, structural and molecular biology techniques.
Accurate knowledge of virus structure and biology is fundamental to both the discovery of antiviral drugs and the design of new, efficient virus-based biotechnological tools.
Research Lines
We investigate the structural and physical determinants of complex virus assembly, focusing on adenoviruses (AdV), pathogens and vectors in nanobiomedicine. Our achievements include: describing the physical and structural changes that modulate the stability of human AdV type 5 (Ad5) during maturation, and therefore its infectivity; demonstrating the existence of internal pressure in a DNA virus packing histone-like, condensing proteins; locating genome packaging factors in the capsid, and determining the mechanism by which they are removed during maturation; unveiling the unsuspected roles of the genome condensing proteins in AdV maturation and entry. We have localized the AdV assembly factory in the nucleus of the infected cell, and proposed a new, concerted assembly and packaging model for AdV. Additionally, our work is broadening our knowledge on the architectural variability of adenoviruses by solving structures of complete virions belonging to scarcely explored species and genera, with potential as alternative vectors.

In the future, we intend to delve into the molecular details of AdV assembly, and extend our range of experimental systems to other viruses structurally related to AdV. Fundamental questions to address are: how the viral genome is encapsidated; how virus particle stability is modulated throughout the infectious cycle; what is the architecture of the non-symmetric components of the viral particle; and what are the structural organization and physicochemical properties of newly discovered viruses of ecological relevance. The overall objective is to increase our knowledge on the structural diversity and morphogenesis of complex viruses. This knowledge will promote the development of antiviral drugs and the design of biological-based nanoparticles for use in nanotechnology and nanomedicine. Ultimately, it will help us understand the evolution of these viruses and their role in the development of life on Earth.

Publications
Group Members
Group Leader
Carmen San Martín
Staff scientists
Gabriela N. Condezo Castro
Marta Martínez
Postdoctoral researchers
José Gallardo Hernanz
Esther M Gonzalez Almela (MSCA fellow)
PhD candidates
Darío Lago Espartero
Sara Otaegi Ugartemendia
UAM visiting scientist
Roberto Marabini

Funding & International Projects
News
iAds: Utilización de vectores de adenovirus para vacunas y transferencia de genes
20 de Febrero 2024 El proyecto iAds busca maximizar el potencial de los vectores de adenovirus para su uso en aplicaciones tales como las vacunas y la transferencia génica. Su objetivo persigue la búsqueda de soluciones en áreas médicas no cubiertas hasta ahora...