Emergent Spatiotemporal Dynamics of Gene Regulatory Network motifs in different biological contexts

Spatiotemporal pattern formation plays a key role in various biological phenomena including Epithelial-Mesenchymal Transition (during cellular differentiation and cancer initiation). Here, we explore the bio-molecular basis of reaction-diffusion systems due to gene regulation through transcription, protein dimerization, and growth-modulating host-circuit interaction. Spatiotemporal multi-stable patterns are formed due to the coupling of the transcriptional toggle switch and toggle triad and their molecular diffusion in one- and two-dimensional space. In another setup of a diffusible cellular environment by a motif with non-cooperative positive feedback, that imposes a metabolic burden on its host, emergent spatiotemporal bistability is obtained. Spatiotemporal diffusion coupled with competitive protein-protein interactions (homo- and hetero-dimerization) and autoregulatory feedback, prevalent in natural multi-stable circuits induces higher order spatiotemporal multistability — quadra-, hexa-, and septa-stability. These analyses offers valuable insights into the design principles of pattern formation facilitated by these network motifs, and suggest mechanistic underpinnings of biological pattern formation.