Virus-host interaction is an extraordinarily powerful probe if one wishes to explore the inner workings of the cell. Being viruses obligate cell parasites, they have evolved extremely sophisticated strategies in order to take control of their host, and studying such strategies is bound to reveal a great deal about the cell itself. However, the exact details of the interaction are sometimes elusive: slight genomic or epi-genomic differences in either the virus or the host can result in completely different outcomes for the infection. For this reason, only studies combining a wide variety of techniques are likely to be successful.
Due to the development of high-throughput techniques in recent years, biological experiments are now more and more reliant on datasets of unprecedented volume and complexity. One of the main drivers toward big-data biology has been the astounding progress in sequencing technologies. A single sequencing experiment can as of today easily produce an amount of data of the order of a TB, equivalent to the content of a modern hard-drive. In addition, several sequencing protocols are usually combined together in order to provide a better understanding of what is going on in the biological system under study. This new situation poses unprecedented challenges.
The activity of the Integrative Biology group focuses on the application of several modern high-throughput technology to the profiling of virus-host interaction. Bioinformatics tools and integrative methods play a crucial role in extracting relevant information from high-throughput data and interpreting it. We apply high performance scientific computing to integratively analyse “omics” data in order to advance scientific understanding of biological information and create a principled basis for biosciences. In livestock animal virology, this is relevant for understanding disease outbreaks, for quantifying their risk, for dissecting the defence mechanisms against viral diseases and for developing effective vaccines.
Our research is centred on integrative analyses of molecular data, like high-throughput sequencing of infected cells and viruses obtained with a variety of protocols (for instance sequencing of RNA, sequencing of chromatin markers, or ribosome profiling). Ongoing projects are centered on a global understanding of the molecular and system biology of complex viruses, elucidating their systems biology, their mechanism of action and, where applicable, the determinants of their cancerogenicity. From the side of the host we focus on the immune response and on fostering the rational design of improved vaccines. Other research interests include viral phylogenetics, phylodynamics and phylogeography; viral evolution and quasispecies, i.e. the dynamics of genetic diversity in viral populations; and population genetics of viruses and hosts.
Recent and ongoing projects in bioinformatics include:
- molecular biology of infection by Marek's disease virus and other avian viruses
- sexual development in mosquitoes
- phylogeography of foot-and-mouth disease virus
- comparatively studying methods for reconstructing evolution and transmission of foot-and-mouth disease virus based on whole genome sequences
- characterising transcriptomic responses to avian influenza infections and the impact of interferon pre-treatment on these responses
- developing computational methods for identifying packaging signals in orbiviruses and and other viruses with segmented genomes
- development of an integrated information system with extensible bioinformatics capabilities for the Reference Laboratories.
Methods developed in the past by members of the group have found direct application in several fields of biomedicine and biotechnology. Some relevant examples include antibody production, the study and treatment of disease genomics (Chronic Lymphocytic Leukemia, HLA bone marrow genotyping, characterization of health and disease molecular phenotypes), the conservation of endangered species (Iberian lynx), the genetic improvement of commercial livestock breeds (Iberian pig) and crops (tomato).
The Integrative Biology and Bioinformatics group provides expertise in analysing molecular data and collaborates with researchers across the Institute to advance our scientific understanding of the biology of viruses and their animal or human hosts. The group develops and maintains the Institute’s scientific computing infrastructure and develops algorithms and computational tools, e.g. for reconstructing transmission trees during outbreaks of animal diseases such as foot-and-mouth disease. Such tools are important for monitoring diseases and for devising effective measures to control them.