Agenda
05/06/2013 - 12:00 - Auditori PRBB

Complete understanding of a living system: how far we are?


Scientific sessions, CRG Group Leader Seminars

Luis Serrano

Design of Biological Systems Group, Systems Biology Programme, CRG



Understanding life, its complexity and the forces that conform evolution is the Holy Grail in biology. In our lab we have undergone the full quantitative analysis of a small bacterium, Mycoplasma pneumoniae, with the final goal of fully understanding this organism and engineer it for human therapy. We analyzed and characterized the metabolic network of M. pneumoniae in great detail, integrating data from different -omics analyses under a range of conditions into a constraint-based model backbone. We systematically investigate the interplay of protein phosphorylation with other post-transcriptional regulatory mechanisms in the genome-reduced bacterium.

The results imply previously unreported hidden layers of post-transcriptional regulation intertwining phosphorylation with lysine acetylation and other mechanisms that define the functional state of a cell. We quantitatively analysed the proteome, protein half-lifes and protein complexes providing a first blueprint of the minimal protein cellular machinery required for life. We analyzed its transcriptome with unprecedented resolution and found that frequent antisense transcripts, alternative transcripts, new short RNAs associated to transcription start sites and multiple regulators per gene imply a highly dynamic transcriptome, more similar to that of eukaryotes than previously thought. We used Single-Molecule Real-Time (SMRT) sequencing to determine its DNA methylome with single-base resolution. Taking advantage of the minitransposon technique we obtained a high-quality essentiality map at base-pair resolution and quantified the essentiality of all functional elements including coding, non-coding genes and intergenic putative structural elements.

Strikingly, we found that both non-coding regions and short protein coding genes that were often overlooked in previous essentiality studies are as highly essential as long protein coding genes. We have also determined the 3D structure of the bacterial chromosome and map all DNA binding proteins on it. All this data revealed a surprising degree of complexity for a bacterium with less than 700 coding genes and indicates that a quantitative understanding even of a simple organism is a daunting task.

Biography:

Luis Serrano is a Systems and Synthetic Biologist working on the quantitative understanding and engineering of living systems. He did hisPhD at the CBM in Madrid on microtubule structucture anf unction, then he did 4 years postdoctoral at the MRC in Cambridge UK working on protein folding. In 1992 he became group leader at the EMBL in Heidelberg, Germany and was promoted to Senior Scientist in 1998 and Coordinator of the Structural and Computational Biology program in 2001. In 2007 he came back to Spain to the CRG and appointed CRG Director in 2011. He has being scientific founder of four Biotech companies and published more than 3000 articles in international journals. He got the Marie Curie Science excellence award and the premi ciutat de Barcelona. In 2008 he obtained an advanced ERC grant. The work of his group is focused on a small model bacterium, M. pneumoniae and on signal transduction in eukaryotes and its relationship to disease.