RESERACH SUMMARY

Signals continuously impinge on cells, modifying their behaviour. This can be understood at three levels. At a population level, signals could modify the distribution of cell classes in a population, influencing core cell processes such as cell renewal in stem cell niches. At the intracellular pathway level, signals are effectively sensed and processed by combinations of genetic circuits. An open question is how these circuits distinguish signal from noise, and how circuit structure might limit this ability.

Finally, at the signal response level, transcriptional control is fundamental to activate adequate responses. This implies the ability of transcriptional factors to distinguish specific nucleotide sequences in the genome.

In the last two years, we have analysed these three aspects of signal processing in the lab

1) Signals and populations

Competition for the survival factor Dpp leads to the proliferation of one class of cells (the winners) at the expense of other (loser) cells; both types exhibit normal growth in homotypic environments. Recent studies in Drosophila demonstrated the role of the dMyc protein in this process. We examined competition in the (Drosophila) ovary stem-cell niche, and showed that differential expression of dMyc triggers competitive interactions. We also presented data in support of the hypothesis that such ongoing competition –between high dMyc stem cells and low dMyc differentiating daughters– increases the efficiency of the differentiation program.

2) Signals and genetic circuits

We considered different types of signals acting on a two-component module to theoretically analyse information processing by genetic circuits. We showed that the presence of feedback in the module imposes a trade-off on amplitude and frequency detection. A direct interaction between the signal and the output species, in a type of feed-forward loop architecture, greatly modifies these trade-offs. Our study emphasised the limits imposed by circuit structure on its stimulus response, and the paradoxical advantage of improving detection with noisy circuit components.

3) Signals and transcriptional control

Transcription factors (TF) commonly act as effectors of cell signal processing by binding DNA sequences adjacent to the response genes whose production they regulate. Could a wide-coverage recognition code between interacting amino acids (of the TF) and nucleotides be found? Our analysis suggested that a set of relatively consistent recognition rules does apply for the extensive LacI family of TF. These rules could ultimately act as a blueprint for the synthetic redesign of TF with new specificities .