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Presentation

Our research group focuses on the study of evolutionary processes at multiple scales and the application of acquired knowledge for improving the state of health of human populations. This description is, of course, general and ambiguous; thus, our research can be substantiated by a number of research activities, which are detailed below:

  • Epidemiology and evolution of pathogenic microorganisms. The access to genetic information (genome and gene sequences) allows us to enquire into the recent history of microorganisms (usually bacteria and viruses) and the evolutionary processes that act or have been acting on them. This allows for their tracking and monitoring, in order to trace the origin of their transmission routes, the introduction and expansion of genes and drug-resistant variants, etc.

 

  • Evolutionary systems biology. Recent developments in high-throughput sequencing techniques and bioinformatics have made it possible to reconstruct the evolutionary history of the organisms, their genes and genomes, as well as of the components of the different systems that integrate them. Applying these methodologies to pathogenic organisms and their hosts provides us with a better understanding of their pathogenesis, as well as of the alternatives and possibilities available to fight them.

 

  • Viral mutation and evolution (VIRMUT). Mutation is the definitive source of genetic variation, making it a key factor in explaining the large variability and the rapid evolution of RNA viruses. In this field, we have estimated the mutation rates of animal viruses, plant viruses and bacteriophages (both RNA and DNA). Currently, we are working on estimating in vitro and in vivo mutation rates of different human viruses that are of great biomedical relevance, such as the HIV-1 or the hepatitis C virus. Through the use of diverse experimental approaches, we intend to identify previously unknown mechanisms of diversity generation in RNA viruses.

 

  • Biological robustness and complexity. The mutational or genetic robustness of organisms, i.e. their ability to tolerate mutations, determines the strength of natural selection and plays an important role in evolution. By means of the targeted mutagenesis technique, we have characterised the distribution of mutational effects on the biological fitness of diverse RNA viruses. This has enabled us to observe the notably low levels of robustness. Furthermore, our group has proposed the existence of a correlation between epistasis (interaction between genes and loci) and genomic complexity. Systems biology provides tools for testing these predictions.

 

  • Experimental evolution of oncolytic viruses. Several RNA viruses exhibit a certain degree of spontaneous selectivity towards cancerous cells, which makes them potential candidates for the development of therapeutic applications. The vesicular stomatitis virus (VSV), which is typically used in our laboratory for experimental evolution studies, is an RNA virus with natural oncolytic activity. VSV’s adaptation to different cancer cell lines by experimental evolution will allow us obtaining potential oncolytics, as long as it implies a significant decrease of its efficacy in primary cells. Candidate viruses will be tested in vivo through infections in mice.