La biologia de sistemes: la biologia del segle XXI?

Al final del segle xx un nou món va emergir dins la ciència, la biologia de sistemes. Aquest terme, que molts consideren una paraula de moda, està ben establert en la comunitat científica. Fins i tot disposem de diversos instituts o departaments a Europa i els Estats Units amb aquest nom. La definició de biologia de sistemes ha esdevingut un dels grans dilemes per als científics. L?ampli ventall de definicions va des de col·leccions de dades fisiològiques amb llistes de parts moleculars quantificades (p. ex., gens, nivells d?expressió, localitzacions), fins a la modelització matemàtica abstracta de processos biològics. L?escala en què se centra la biologia del sistemes és també un afer discutit; una proteïna minúscula pot ser un sistema biològic tan complex (encara no sabem com es plega) com un ecosistema sencer amb milers d?espècies. El terme biologia del sistemes probablement augmentarà les seves accepcions fins a arribar a un primer pla i les oportunitats de finançament haurien de ser agafades seriosament per les comunitats científiques. En principi la biologia de sistemes ofereix l?oportunitat d?entendre processos biològics i obre la possibilitat de modificar-los i fer enginyeria d?una manera racional (biologia sintètica). La biologia de sistemes és aquí per quedar-se i obrir camí a teràpies noves, a la medicina individualitzada i, en combinació amb la biologia sintètica, a l?enginyeria racional dels sistemes vius.Systems biology: The biology of the XXI century? At the end of the 20th century a new world emerged in science, systems biology. This term that many consider a buzzword is now well established in the scientific community and we even have several institutes or departments in Europe and the United States bearing this name. However, scientists remain in a quandary about defining Systems Biology. Definitions range from collections of physiological data with quantified molecular parts lists (e.g. genes, expression levels, localizations) to abstract mathematical modelling of biological processes. The scale at which Systems Biology focuses is also a matter of contention: a tiny protein can be a complicated biological system (we still do not know how it folds) as is obviously an entire ecosystem with thousands of species. The term «Systems Biology» will probably broaden its meaning even further as it is now under the limelight and funding opportunities have to be taken seriously by very diverse scientific communities. In principle Systems Biology offers an opportunity to understand biological processes in a way in which we could modify and engineer them in a rational manner (Synthetic Biology). Systems Biology is here to stay and will open the way to new therapies, individualized medicine and, in combination with synthetic biology, to the rational engineering of living systems

La biologia de sistemes: la biologia del segle XXI?

Al final del segle xx un nou món va emergir dins la ciència, la biologia de sistemes. Aquest terme, que molts consideren una paraula de moda, està ben establert en la comunitat científica. Fins i tot disposem de diversos instituts o departaments a Europa i els Estats Units amb aquest nom. La definició de biologia de sistemes ha esdevingut un dels grans dilemes per als científics. L?ampli ventall de definicions va des de col·leccions de dades fisiològiques amb llistes de parts moleculars quantificades (p. ex., gens, nivells d?expressió, localitzacions), fins a la modelització matemàtica abstracta de processos biològics. L?escala en què se centra la biologia del sistemes és també un afer discutit; una proteïna minúscula pot ser un sistema biològic tan complex (encara no sabem com es plega) com un ecosistema sencer amb milers d?espècies. El terme biologia del sistemes probablement augmentarà les seves accepcions fins a arribar a un primer pla i les oportunitats de finançament haurien de ser agafades seriosament per les comunitats científiques. En principi la biologia de sistemes ofereix l?oportunitat d?entendre processos biològics i obre la possibilitat de modificar-los i fer enginyeria d?una manera racional (biologia sintètica). La biologia de sistemes és aquí per quedar-se i obrir camí a teràpies noves, a la medicina individualitzada i, en combinació amb la biologia sintètica, a l?enginyeria racional dels sistemes vius.Systems biology: The biology of the XXI century? At the end of the 20th century a new world emerged in science, systems biology. This term that many consider a buzzword is now well established in the scientific community and we even have several institutes or departments in Europe and the United States bearing this name. However, scientists remain in a quandary about defining Systems Biology. Definitions range from collections of physiological data with quantified molecular parts lists (e.g. genes, expression levels, localizations) to abstract mathematical modelling of biological processes. The scale at which Systems Biology focuses is also a matter of contention: a tiny protein can be a complicated biological system (we still do not know how it folds) as is obviously an entire ecosystem with thousands of species. The term «Systems Biology» will probably broaden its meaning even further as it is now under the limelight and funding opportunities have to be taken seriously by very diverse scientific communities. In principle Systems Biology offers an opportunity to understand biological processes in a way in which we could modify and engineer them in a rational manner (Synthetic Biology). Systems Biology is here to stay and will open the way to new therapies, individualized medicine and, in combination with synthetic biology, to the rational engineering of living systems

Estudio de la expresión génica y la división celular en Mycoplasma genitalium

Descripció del recurs: el 27 de juny de 2011Los micoplasmas son bacterias sin pared celular que pertenecen a la clase Mollicutes. Estos microorganismos se caracterizan por su pequeño tamaño y por tener un genoma reducido con un bajo porcentaje de C+G. Muchas especies de mycoplasma actúan como parásitos y patógenos de un amplio rango de huéspedes, causando enfermedades comunes en humanos. Por ejemplo, Mycoplasma genitalium, objeto de esta tesis, es el causante de la uretritis no gonocócica. La secuenciación del genoma de algunos micoplasmas ha favorecido el conocimiento de la fisiología y genética de estos microorganismos, pero algunos mecanismos como la regulación de la expresión génica y la división celular siguen siendo aún un misterio por desvelar. M. genitalium, con tan sólo 525 genes, es considerado un modelo de célula mínima. Posee el genoma más pequeño de entre todas las bacterias que se pueden cultivar axénicamente, siendo así un candidato ideal para el estudio de los procesos biológicos con el mínimo número de genes implicados. El trabajo presentado en esta tesis se divide en tres capítulos independientes. En el primero se estudia la regulación de la expresión génica en M. genitalium y M. pneumoniae. El trabajo con M. pneumoniae fue llevado a cabo durante una estancia en el laboratorio del Prof. J. Stülke (Göttingen, Alemania). Este primer trabajo dio lugar a un artículo publicado en la revista Microbiology. La obtención de un mutante por transposición de M. genitalium que deleccionaba el gen ftsZ, descrito como esencial para la división celular en la mayor parte de bacterias, derivó en el segundo capítulo de esta tesis. En este segundo trabajo se investiga la división celular en micoplasma en ausencia de este gen. Este estudio ha sido publicado recientemente en la revista Molecular Microbiology. Por último, con el objetivo de profundizar en el tema de la división celular en micoplasma, en el tercer capítulo se analiza la funcionalidad del gen mraZ, que junto con mraW, mg223 y ftsZ conforma el operón de división celular de M. genitalium.Mycoplasmas are the smallest and simplest free-living microorganisms. They are members of the Mollicutes class which is characterized by the absence of cell wall and by having genomes with a low G+C content. Despite this apparent simplicity, some mycoplasma species are parasites and pathogens of a wide range of hosts. For instance, Mycoplasma genitalium, which is the object of this thesis, is the agent of non-gonococcal and non-chlamydial urethritis. Genome sequencing has advanced the knowledge concerning the physiology and genetics of these microorganisms, but some mechanisms such as the regulation of gene expression and the cell division remain unclear. With only 525 genes M. genitalium is considered a model of minimal cell, since it has the smallest genome of any microorganism that can be grown in a pure or axenic culture. It is considered a perfect candidate to study biological processes with the minimal set of genes. This thesis is divided into three independent chapters. In the first one we study the regulation of gene expression in M. genitalium and M. pneumoniae. This work was published in 2007 in the journal "Microbiology". A minitransposon insertion was found in the ftsZ gene of M. genitalium, indicating that this gene was not essential for cell division in this microorganism. In the second chapter of this thesis we investigate the cell division process in M. genitalium in the absence of ftsZ. This work was recently published in the journal "Molecular Microbiology". Finally, to gain insight into the cell division process in mycoplasma, in the third chapter we analyze the function of the mraZ gene, which together with mraW, mg223 and ftsZ comprise the cell division operon of M. genitalium

Bacterial antisense RNAs are mainly the product of transcriptional noise

cis-Encoded antisense RNAs (asRNAs) are widespread along bacterial transcriptomes. However, the role of most of these RNAs remains unknown, and there is an ongoing discussion as to what extent these transcripts are the result of transcriptional noise. We show, by comparative transcriptomics of 20 bacterial species and one chloroplast, that the number of asRNAs is exponentially dependent on the genomic AT content and that expression of asRNA at low levels exerts little impact in terms of energy consumption. A transcription model simulating mRNA and asRNA production indicates that the asRNA regulatory effect is only observed above certain expression thresholds, substantially higher than physiological transcript levels. These predictions were verified experimentally by overexpressing nine different asRNAs in Mycoplasma pneumoniae. Our results suggest that most of the antisense transcripts found in bacteria are the consequence of transcriptional noise, arising at spurious promoters throughout the genome.This work was supported by the European Union Seventh Framework Programme (FP7/2007–2013), through the European Research Council (232913); Fundación Botín, the Spanish Ministry of Economy and Competitiveness (BIO2007-61762); National Plan of R + D + i; ISCIII—Subdirección General de Evaluación y Fomento de la Investigación (PI10/01702); European Regional Development Fund (to the Institució Catalana de Recerca i Estudis Avançats research professor L.S.); and Spanish Ministry of Economy and Competitiveness, “Centro de Excelencia Severo Ochoa 2013–2017” (SEV-2012-0208). A.L. received grant BFU2012-39816-C02-01 from the Spanish Ministry of Economy and Competitivity cofinanced by FEDER (Fondo Europeo de Desarrollo Regional) funds

Tuning gene activity by inducible and targeted regulation of gene expression in minimal bacterial cells

Altres ajuts: predoctoral fellowship from the Generalitat de Catalunya (FI-DGR 2014)This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposesFunctional genomics studies in minimal mycoplasma cells enable unobstructed access to some of the most fundamental processes in biology. Conventional transposon bombardment and gene knockout approaches often fail to reveal functions of genes that are essential for viability, where lethality precludes phenotypic characterization. Conditional inactivation of genes is effective for characterizing functions central to cell growth and division, but tools are limited for this purpose in mycoplasmas. Here we demonstrate systems for inducible repression of gene expression based on clustered regularly interspaced short palindromic repeats-mediated interference (CRISPRi) in Mycoplasma pneumoniae and synthetic Mycoplasma mycoides, two organisms with reduced genomes actively used in systems biology studies. In the synthetic cell, we also demonstrate inducible gene expression for the first time. Time-course data suggest rapid kinetics and reversible engagement of CRISPRi. Targeting of six selected endogenous genes with this system results in lowered transcript levels or reduced growth rates that agree with lack or shortage of data in previous transposon bombardment studies, and now produces actual cells to analyze. The ksgA gene encodes a methylase that modifies 16S rRNA, rendering it vulnerable to inhibition by the antibiotic kasugamycin. Targeting the ksgA gene with CRISPRi removes the lethal effect of kasugamycin and enables cell growth, thereby establishing specific and effective gene modulation with our system. The facile methods for conditional gene activation and inactivation in mycoplasmas open the door to systematic dissection of genetic programs at the core of cellular lif

Remoted instantaneous frequency measurement system using optical mixing in highly nonlinear fiber

A novel instantaneous frequency measurement using all optical mixing is demonstrated. This system can provide a measurement of RF frequency while requiring no high speed electronic components and remoting all components of the measurement system to the receiver