Our group started originally over forty years ago. A major founding milestone was the postgraduate study of Dr Jose Viña with the late Sir Hans Krebs at the University of Oxford. This has led the whole Group to a "metabolic-oriented approach to problems" as it could not be otherwise stemming from Sir Hans Krebs. Upon his return to Spain, Dr Viña started a small group in the University of Valencia that has been working, on and off, for the last thirty-five years. Sometimes Dr Viña was away from the University of Valencia, but the seed of the Group had been sown. Very seriously established scientists like Dr Federico Pallardo, Dean of the Faculty of Medicine - University of Valencia, Dr Juan Sastre, Dr Jose Estrella, Dr Guillermo Saez, all of them professors of biochemistry or physiology at the University of Valencia, the late Dr Navarro, University of Cadiz and Dr Juan Llopis, University of Albacete started their scientific work in this group and latar established their own successful independent groups.Some twenty years ago the major hard-core members of the Group in its present form came to the laboratory and these include Dr Ana Lloret, Dr Carmen Gomez-Cabrera and Dr Consuelo Borras. All the three are now very well established scientists and form the backbone of the Group. Other permanent members include Dr Juan Gambini, Dr Marta Ingles, and Dr Gloria Olaso. For over twenty years we have been blessed by the help of Marilyn Noyes; she has been integrated in the Group for all these years and we hope for many more to come.

Our collaborations with many colleagues, indeed friends, in Spain are so frequent that we would not like to highlight any of them. We are delighted to have all these friends around the country.

We have established close connections with other labs around the world. Some examples include the labs of Dr Giovanni E Mann and of Dr Malcolm Jackson in the UK, Dr Giuseppe Poli in Italy, Dr Helmut Sies and Dr Tilman Grune in Germany, Drs Delamarche in France, Drs Boveris and Dr Fraga in Argentina and Dr Bruce Ames, Dr Packer, Dr Orr and Dr Li Li Ji in the US.
There is a continuous renewal of our Group and we are happy to have had temporary members in the team from Spain, not only from Valencia, but also from France, Italy, Portugal, Morocco, Argentina, Sahara, or Japan. The names of Dr Frédéric Derbré, Dr Gaetano Serviddio, Dr Diana Rus, Dr Jelena Marcovic, Dr Nancy Mora and Dr Mika Jikamaru are just a few examples of this international collaboration. These have been indeed very interesting people who have come to us and have contributed to the pleasant spirit of this team. We consider ourselves as a "scientific family" and hope we will continue contributing to biomedical research and enjoying life at our laboratory.

Our research group is dedicated to a multi-scale study of evolutionary processes and the application of acquired knowledge to improve the health status of human collectives. This description is necessarily generic and ambiguous, and it focuses on a series of research activities that are detailed below:

• Epidemiology and evolution of pathogenic microorganisms. We take advantage of the research capability granting us access to genetic information (gene sequences and genomes) on recent history and evolutionary processes that act and have acted on microorganisms, normally bacteria and viruses, and enable follow-up and monitoring as a way to track the origin of transmission paths, the introduction and expansion of genes and drug-resistant variants, etc.
• Evolutionary systems biology. The recent developments in massive sequencing techniques and bioinformatics allow a rebuild of the evolutionary history of organisms, their genes and genomes, as well as that of components formed by all the various systems. The implementation of these methodologies in pathogenic organisms and their hosts makes us reach a better understanding on pathogenesis as well as alternatives and possibilities to act against them.
• Mutation and viral evolution (VIRMUT). A mutation represents the ultimate source for genetic variation and, as such, a key factor that clarifies the great variability and rapid evolution of ARN viruses. In this field, we estimated the virus mutation rate in animals, plants and bacteriophages (RNA as well as DNA ones). As of today, we are working on an in vitro and in vivo mutation rates estimate of different, biomedically relevant human viruses, such as HIV-1 or hepatitis C. With the use of different experimental approximations, we count on being able to detect mechanisms yet unknown in the creation of RNA diversity.
• Biologic complexity and robustness. The organisms’ capacity to withstand mutations (genetic or mutational robustness) determines the strength of natural selection and plays an important role in evolution. With the directed mutagenesis technique, we characterised the distribution of mutational effects based on the biological efficacy of various RNA viruses. This allowed us to observe notoriously low robustness levels. Moreover, our group pointed out the existence of a correlation between epistasis (interaction between genes or loci) and genomic complexity. The Systems Biology currently offers tools that allow to test these predictions.
• Experimental evolution of oncolytic viruses. Different RNA viruses show a certain degree of spontaneous selectiveness towards cancer cells, which is convenient in potential candidates for the development of therapeutic applications. The vesicular stomatitis virus (VSV) is a RNA virus with natural oncolytic activity and it’s usually used in our laboratory for studies on experimental evolution. The VSV adaptation to different cancer cell lines by experimental evolution will enable the obtainment of potential oncolytics, provided it results in a relevant decrease of its efficacy in primary cells. The virus candidates will be tested in vivo through infections in mice.

The Gastrointestinal Infection Research Group of the Department of Microbiology and Ecology works in the Faculty of Medicine and Dentistry and is linked to the Clinical Microbiology Service of the Hospital Clínico Universitario de Valencia.

Our main objective is to investigate the pathogenic mechanisms of infectious agents that produce gastrointestinal pathology, mainly viruses (rotavirus and norovirus), as well as the immune response caused by these infections. Rotavirus and norovirus produce gastroenteritis that affect children, although noroviruses can also infect people of any age, often causing epidemic outbreaks. We study the immunological mechanisms of protection against these infections, as well as the molecular determinants that condition susceptibility to them.

Our research consists of the design of new chemical compounds, especially new drugs, using topological descriptors. The main task of our group has been the use of topological indices in reverse to the conventional, i.e. instead of predicting properties of molecules already existing, our group generates new molecules just from the existing properties, obtaining, thus, molecular fingerprints which enable the search for new compounds with improved features. Currently we use a large number of topological indices -most of them original- which allowed us to design and select new lead compounds in the following fields: Analgesics, antibacterials, hypolipidemics, hypoglycaemics, bronchodilators, antivirals, antihystaminics, antimalarials, antineoplastics and anti-Alzheimer. Moreover, good results have been obtained also in Green Chemistry by predicting reaction pathways, yields and times, which allows designing more sustainable and profitable chemical processes. These results demonstrate the great effectiveness of the topological method used, to the point that it could be considered as an alternative and independent way of describing molecular structures. The results of our research have also been reflected in more than 100 research articles published in international journals, book chapters, patents, conferences, congresses, etc.