The Environmental and Biomedical Viruses Lab is located at the Insitute for Integrative Systems Biology (I2SysBio, UV-CSIC). Research at the EnBiVir lab is focused in the isolation and detection of viruses in nature with biomedical applications. Environmental virology, viral emergence, virus evolution, and phage discovery in the biomedical context, are the main research lines. Phages are ubiquitous in the environment and immensely diverse, making phage discovery a powerful source of new therapies against pathogenic bacteria, due to the emergence of multidrug-resistant strains. In addition, the lab is interested in environmental epidemiology, mainly in SARS-CoV-2 detection in wastewater and other natural environments, as a tool for monitoring populations and as early detection tool in surveillance. In addition, the group is interested in translational research, and has transfer contracts with national companies with biomedical and biotech purposes.
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.
Main research lines:
- Symbiosis evolution: The Symbiosis is an important factor for the promotion of evolutionary novelties. Studying it requires a joint analysis of the eukaryote host and its closely associated microorganisms by employing genomics and metagenomics. Moreover, the symbiosis of insects and humans is studied in a fundamental manner.
- Synthetic biology. The study of genomes of a microorganism variety offers clues for the comprehension and synthesis of minimal cells with applications in biomedicine, bioremediation and biotechnology.
- Genetic study of aphids: Taxonomy and reproductive polyphenism. Identification of genes and regulating channels for aphid reproduction (parthenogenesis vs sexuality).
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.
The fundamentally basic research activity of the ParaSalut group covers different aspects of the relationship between health and parasites, in both humans and animals carrying parasitic diseases or their models. The group presents lines of work on parasitic diseases caused by Protozoa, as well as Helminths and Arthropods. All the lines are already in progress and have numerous publications, as shown on the group members’ resumes.
Protozoa: One of the group’s research lines focuses on the influence of intestinal parasites (mainly protozoa) on human nutrition, given that said parasites interfere directly or indirectly with the nutrient absorption processes, maldigestion and / or malabsorption. Therefore, this line consists of two main objectives: 1) study on the relationship between intestinal parasites and food intolerances to carbohydrates, and 2) studies on the relationship between intestinal parasites and mother-child nutrition, as well as the analysis of the nutritional status of mothers and children and the effect of parasitosis on child development.
Helminths: Different aspects of helminthic diseases are addressed with a focus on epidemiology, ecology and parasite-host relationships.
Epidemiology / ecology: There are two lines addressing aspects on epidemiology and ecology of diseases caused by helminths. One of them analyses the study on biological cycles, transmission and population dynamic of helminths in murine models that have shown to be good bio-indicators of the parasite-host relationship. These studies are complemented by the line working on the creation of Geographical Information Systems with the use of satellite images and thematic maps for epidemiology modelling and the transmission of human and animal parasites, and the influence of climate change on them. Likewise, studies on food-transmitted parasitic diseases are addressed in another line in which the study of anisakiasis in fish for human consumption represents its basic pillar.
Parasite-host relationships: the establishment of a parasitic disease results from the parasite succeeding over the host. The analysis for the established relationships between both are fundamental to know the factors said establishment depends on, thus enabling the implementation of adequate preventive measures. Likewise, the specificity of this relationship is a tool for the improvement of current diagnostic methods. In these parasite-host relationships, extracellular vesicles (EVs) have lately proved to be a valuable instrument for these purposes.
The ParaSalud group develops a line on the study of EVs in different helminths of human and veterinary interest. Said EVs are isolated and characterised by their composition (proteins, miRNAs) and their use as target molecules for diagnosis, treatment and / or vaccination is experimentally evaluated. This previously undertaken research line is reinforced by other lines from the group working on the study of parasite-host relationships by techniques generally referred to as “omics”, including genomics, transcriptomics and proteomics.
The line on human Taeniasis / Cisticerosis is part of both aspects: epidemiological studies of materials from different countries, and ultrastructural as well as secretomics studies of the infective form of human cisticerosis, the egg.
Arthropods: Equally important are ectoparasite arthropods, considering that in addition to being vectors of parasitic diseases, they have their own pathogenic potential. The Medical Entomology line carries out the diagnosis and epidemiologic analysis of mosquitos populations, lice, bedbugs and myisis cases.
