Identification of signals that depend on the static curvature of the DNA.
The relevance of curved regions of DNA in different biological processes such as recombination, replication, transcriptional regulation, among others, has been studied for more than 20 years.
In most of the above processes, the analysis of regions with static curvature of the DNA has exclusively contemplated discrete sequence models not larger than a couple of hundred base pairs. In contrast, the characterization and possible role of static DNA curvature of the genomes considered in its entirety is incipient. The availability of the genomic sequences of different organisms has allowed us to generate a line of theoretical-experimental study whose objective is to analyze the biological role of the curved regions of DNA.

Transcriptional attenuation is a regulation element in bacterial organisms whereby the synthesis of an operon mRNA can be terminated prematurely in response to different intracellular signals. This choice between total or premature transcription of the operon is mediated by the formation of two mutually exclusive secondary structures in the leading region of the mRNA and correspond to independent rho transcriptional antiterminators or terminators.
The programs developed to look for transcriptional attenuators are constructed in a modular way, so that each one of them verifies one of the several conditions that a sequence must contain to be considered as said regulatory element. Among the most important conditions are the following: i) the free energy of the secondary structures that form it, ii) that these structures are mutually exclusive, iii) that are in the regulatory region and close to the structural gene immediately downstream.

In E. coli and other Gram negative bacteria, the "choice" between terminator or antiterminator formation is mediated by the rate of synthesis of a small peptide encoded by the operon's leading region, which in turn depends on the intracellular availability of the loaded tRNA corresponding to the metabolic pathway being regulated.
In B. subtilis the attenuation does not depend on the synthesis of any peptide encoded by its leader region but is mediated by proteins that bind to the mRNA leader region. In the case of the tryptophan operon of B. subtilis, the regulator is the TRAP protein (Tryptophan Attenuation Protein) that has the ability to bind to the leader region of the mRNA in the presence of tryptophan amino acid.
We extend this knowledge by analyzing the regulatory regions of Gram positive bacteria whose genome has been sequenced and is publicly available. We have found that the trp operon regulation model is rather an exception to what happens in most Gram positive bacteria where it is common to find that the trp operon is regulated by T-box elements and not by orthologous proteins to TRAP.

It has been proposed that the sequential folding of the structural domains in some proteins, requires a pause that allows said domains to be structured independently or that the cofactor assembly is adequate.
We have statistically analyzed the previous hypothesis by simultaneously considering the distribution of rare codons in families of orthologous genes, not in an isolated and unique way as previously performed for E. coli proteins. Because the preferential use of codons can vary considerably between organisms, we develop an analysis methodology to determine the statistical significance of finding regions with slow codons in a multiple alignment of homologous genes. We are currently conducting a study to locate in the three-dimensional structures of the corresponding proteins, the regions of a possible “translational break” identified in our statistical study.

The information contained in the public databases, as well as the predictions obtained by our group, have allowed us to generate mathematical models that explain the global organization of regulatory networks in cohesive and functionally related groups, in different bacterial model organisms.
These models have managed to explain properties of the biological networks such as evolutionary potential, identification of hierarchical or global vs. local regulators and adaptability of the studied networks. Within this line, our group has worked on the creation of mathematical models that help us predict which regulatory elements are relevant for decision making in various cellular processes.
Our first models have been applied in the description of the dynamics of the interactions that couple the signaling and regulation cascades described in the sporulation and competence of the Bacillus subtilis bacteria.

One of the lines that we have begun to develop in the last 5 years is an integrative study that tells us about the statistical properties of metabolic networks and their relationship with the regulation of genetic expression, all this in order to build models that allow to generate algorithms for the analysis, prediction and reconstruction of metabolic networks in all organisms currently sequenced.

In the last two years, our group has ventured into the development of computational tools available to the community via the World Wide Web (WWW).
For example, we have created a tool for the study of metabolic networks. As well as a database and web page for the analysis of shot-gun metagenomes and their visualization on thematic maps.