Synthetic Gene Oscillators and Their Applications

Tal Danino

The engineering of genetic circuits with predictive functionality in living cells represents a defining focus of the expanding field of synthetic biology. This focus was elegantly set in motion a decade ago with the design and construction of a genetic toggle switch and an oscillator, with subsequent highlights that have included circuits capable of pattern generation, noise shaping, edge detection and event counting.  Here we describe an engineered gene network with global intercellular coupling that is capable of generating synchronized oscillations in a growing population of cells.  Using microfluidic devices tailored for cellular populations at differing length scales, we investigate the collective synchronization properties along with spatiotemporal waves occurring at millimetre scales.  We use computational modelling to describe quantitatively the period and amplitude of bulk oscillations. In addition to the work on the synchronized clock, we will discuss studies on synthetic gene oscillators using a high-throughput microfluidic platform that facilitates automated tracking in single-cells.  We will describe the use of this device to chemically drive synthetic gene oscillators (analogous to the way circadian systems are driven by light) as well
investigation into coupling of additional circuits to oscillators.