Cells are continuously making decisions in response to internal and external cues. How these decisions are regulated by their internal genetic circuitry, how such circuitry evolves, how individual decision-making helps assemble cellular communities, and what are the genetic/genomic factors (e.g., biochemical noise) that limit or interfere with these processes have been the goal of our research over the last years.
Our approach to attack these matters and the specific questions that we worked on have been diverse. Questions do not necessarily appear complex a priori. For instance, we used high-throughput data to ask what determines the position of genes in eukaryotic genomes, a minimal question that we do not fully understand yet [Hurst2006, Hurst2007]. Gene position is important additionally in relation to gene expression noise and plasticity; both features greatly influencing cellular decisions. Notably, expression noise and plasticity can be now quantified genome-wide, and we recently used this type of data to characterize which molecular aspects determine this variability (and how it becomes tuned by Evolution) [Bajic2012].
Following this search of “simple” problems, we analyzed how two-component genetic circuits (arguably one of the simplest regulatory structures) lead to protein oscillations [Guantes2006]. This emphasized the implications that a particular genetic implementation of a given regulatory logic (say a transcriptional vs. a post-translational repression) could have in the dynamics of the circuit. This research underlined in addition how noise interferes with circuit dynamics [Guantes2010]. Our search for design principles of biological circuits can provide valuable information across scales. For instance, properties that we identified for genetic circuits were also applicable to neural circuits [Poyatos2012].
In the wet lab, we characterized several bacterial response programs by (quantitative) single-cell experiments, and the use of fluorescence proteins as reporters. With these techniques we understood the relevance of negative autogenous control in the SOS DNA repair system [Camas2006], or how the dynamical features associated to positive and negative autoregulations contribute to launch the multiple antibiotic resistance (MAR) response [Rodrigo2014]. With the use of Synthetic Biology, we are currently quantifying the single-cell behavior of "developmental" circuits that we have engineered in the bacterium Escherichia coli.
More recently, we started to examine how social structures emerge out of individual decisions. We are particularly interested in communities, or collectives, that rely on cooperation (e.g., due to the presence of public goods), both theoretically [Cavaliere2013] and experimentally. These "social architectures" apply not only to cellular systems, so we hope (again) to identify principles applicable across scales.
Our group is thus a mixture of individuals with different backgrounds that examine a number of related topics with the use of several complementary tools (theoretical and experimental). We make ourselves no promises, but we share the hope that this multidisciplinary and unobstructed pursuit of useless questions will prove to have consequences in the future as in the past [Flexner1939]. Please stay tuned.