PROJECT TITLE: MICROBIAL COMPARATIVE GENOMICS
MEMBERS: 10 RESEARCH GROUP
COORDINATION: FRANCISCO RODRIGUEZ-VALERA
Prokaryotic cells are the main drivers of the planetary ecosystem and not only provide humans with most of our bioactive compounds but represent still a major threat to our health. The study of bacteria has been revolutionized in the last 10 years by the advent of Genomics and the development of Next Generation Sequencing (NGS) technologies. We are now at the initial steps of the high throughput – low cost NGS revolution. Based on different chemistry and nanotechnologies these methods allow the introduction of population biology in the picture. Within this project we plan to apply NGS extensively and to use these new tools to clarify one of the main conundrums of Biology i.e. the genome dynamics of prokaryotes. We anticipate that the study of genome dynamics will clarify many aspects of bacterial evolution, adaptation or population genetics, as well as provide new approaches for biomedical and biotechnological applications. For example, one of the major discoveries of modern microbiology has been the characterization of the total gene pool of a bacterial species, which surprisingly does not reach an end even in model species like E. coli. This typically prokaryotic feature has given rise to the concept of the pangenome, which is central to understand bacterial evolution and has also practical implications. The concept of the pan-genome therefore opens a new way of thinking in Microbiology and Biology at large and Genomics and Metagenomics provide the tool to face this challenge. An obvious approach to define and study a prokaryotic pan-genome is the sequencing of multiple strains from a given species. However, the culturability of different strains in not necessarily equivalent and culture will always introduce some bias. Metagenomics, the direct sequencing of prokaryotic DNA from the environment, allows approaching the genomic diversity of some species without the bias associated to culture. By sequencing many isolates from one species and comparing them to a natural metagenome in which they are abundantly represented we get the equivalent of a motion picture in which the dynamic nature of prokaryotic genomes can be unveiled. Given the enormous flexibility and variability of bacteria, it is of great importance to study different model systems spanning several bacterial groups. We are going to be innovative in two main aspects: Firstly, the methodology to apply involving NGS and next generation genome analysis (NGA); and secondly, in the problem we are trying to solve (genome dynamics and population genomics). To approach this problem it is important to use different model microbes and their habitats since the diversity of prokaryotes is so vast that any individual example is bound to provide biased answers. The different model systems will be studied by comparative genomics and metagenomics, and virtually all the studies will have an applied aspect, ranging from new methods for mutagenesis, new protocols for establishing biodiversity and detecting environmental changes, new approaches to treat and prevent oral diseases or new therapeutic tools by the use of mobile islands and delivered within phage capsids.
One of the key elements of this new stage in biology is that the generation of sequence data is relatively simple and inexpensive but the analysis at all levels becomes the bottleneck to real progress. A gradient of skills is therefore required from the pure biologist to the pure computer scientist and we intend to enhance this kind of framework, both in our team composition and in the training we will undertake through a specialised course in Bacterial Genomics and NGA. Thus, the genomics lab is a new paradigm of multidisciplinary team and must include strong expertise in laboratory experimentation (from molecular biology to classic microbiology, genomics and metagenomics techniques), solid knowledge of the biological system under study (from metabolic inference to microbial ecology, evolutionary theory and systematics), and large capacity for high-throughput data analysis (bioinformatics, database construction and management). The criteria we chose for designing the MICROGEN team was the agglutination of all of these backgrounds when the ten different teams work together and we believe the combination of strong biology with solid cutting-edge experimentation skills and next-generation genome analysis capabilities will take microbiology to a new dimension. In fact, we consider this approach the future of microbiology in the same way as the implementation of molecular techniques in the 80´s became the modern microbiology until now. The group will serve as a nucleating agent that will permit Spanish Microbiology to remain in the mainstream of international Microbiology and to continue being a support to the future of Spanish Biotechnology and Biomedicine.