Mechanisms of pattern formation in developmental systems generally combine complex intracellular genetic circuits with intercellular signaling. In many cases it is difficult to study these mechanisms due to the incomplete knowledge of the components involved and the inherent complexity of natural circuits. I propose to study these principles in a quantitative manner, using a synthetic network approach combined with microfluidic technology. I will initially develop an experimental platform with bacterial strains capable of sending, receiving, and interpreting diffusible signals combined with a microfluidic setup allowing well controlled and quantitative measurements of these strains. Different mechanisms for the formation of morphogen gradients will be studied; in particular their robustness to noise will be compared. I will then extend the system to eukaryotic cells by developing a synthetic signal transduction system. This signaling system will be used to study patterns based on juxtacrine signaling (direct cell-cell signaling). This study could provide a more quantitative understanding of the underlying principles of developmental patterning at the circuit level and may lead to biomedical applications in fields like tissue engineering. ? ?
| Sprinzak, David; Lakhanpal, Amit; LeBon, Lauren et al. (2011) Mutual inactivation of Notch receptors and ligands facilitates developmental patterning. PLoS Comput Biol 7:e1002069 |
| Sprinzak, David; Lakhanpal, Amit; Lebon, Lauren et al. (2010) Cis-interactions between Notch and Delta generate mutually exclusive signalling states. Nature 465:86-90 |
