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Jerome Bonnet

Publications and source records attributed to Jerome Bonnet.

2 recordsLinked to original sources

Analytic framework for stochastic binary biological switches

We propose an analytic solution for the stochastic dynamics of a binary biological switch, defined as a DNA unit with two mutually exclusive configurations, each one triggering the expression of a different gene. Such a device could be used as a memory unit for biological computing systems designed to operate in noisy environments. We discuss a recent implementation of an exclusive switch in living cells, the recombinase addressable data (RAD) module. In order to understand the behavior of a RAD module we compute the exact time dependent distributions of the two expressed genes starting in one state and evolving to another asymptotic state. We consider two operating regimes of the RAD module: fast and slow stochastic switching. The fast regime is \"aggregative\" and produces unimodal distributions, whereas the slow regime is \"separative\" and produces bimodal distributions. Both regimes can serve to prepare pure memory states when all cells are expressing the same gene. The slow regime can also separate mixed states by producing two sub-populations each one expressing a different gene. Our model provides a simplified, general phenomenological framework for studying biological memory devices and our analytic solution can be further used to clarify theoretical concepts in bio-computation and for optimal design in synthetic biology.

Synthetic Biology

Connecting Boolean Integrase Logic gates to a novel alkane control signal via engineered level matching.

Boolean Integrase Logic gates use phage integrases that respond to transcriptional signals to implement logical functions within living cells via DNA recombination. Control of biological systems using these logic gates has many applications, including biomanufacturing, healthcare, or environmental remediation. Gates are highly sensitive to background transcriptional noise producing unwanted integrase expression and uncontrolled, permanent gate switching. Consequently, connecting gates to novel control signals requires time-consuming directed evolution of regions regulating integrase expression. Here we present an approach in which the activity of an alkane biosensor is tuned to match levels of existing integrase control signals. By adjusting AlkS expression, we tuned the transcriptional output of Palkb to match the output of existing integrase controllers. We successfully connected Palkb to two integrases with different transcriptional control requirements and demonstrated the original logic function was conserved. Our method complements directed evolution approaches to connect Boolean integrate logic gates to novel transcriptional sources and will ultimately facilitate the systematic in silico design of gates responding to various control signals.

Synthetic Biology