%0 Journal Article
%T On the functional diversity of dynamical behaviour in genetic and metabolic feedback systems
%A Lan K Nguyen
%A Don Kulasiri
%J BMC Systems Biology
%D 2009
%I BioMed Central
%R 10.1186/1752-0509-3-51
%X We develop an analytical bifurcation analysis based on the stability and the Routh- Hurwitz theorem for a common negative feedback system and a variety of its variants. We demonstrate that different combinations of the feedback strengths of individual loops give rise to different dynamical behaviours. Moreover, incorporating more negative feedback loops always tend to enhance system stability. We show that two mechanisms, in addition to the lengthening of pathway, can lower the Hill coefficient to a biologically plausible level required for sustained oscillations. These include loops coupling and end-product utilisation. We find that the degradation rates solely affect the threshold Hill coefficient for sustained oscillation, while the synthesis rates have more significant roles in determining the threshold feedback strength. Unbalancing the degradation rates between the system species is found as a way to improve stability.The analytical methods and insights presented in this study demonstrate that reallocation of the feedback loop may or may not make the system more stable; the specific effect is determined by the degradation rates of the newly inhibited molecular species. As the loop moves closer to the end of the pathway, the minimum Hill coefficient for oscillation is reduced. Furthermore, under general (unequal) values of the degradation rates, system extension becomes more stable only when the added species degrades slower than it is being produced; otherwise the system is more prone to oscillation. The coupling of loops significantly increases the richness of dynamical bifurcation characteristics. The likelihood of having oscillatory behaviour is directly determined by the loops' strength: stronger loops always result in smaller oscillatory regions.Feedback control mechanisms are vital to the robust functioning of gene regulatory and metabolic pathways. They have been extensively researched over the last two decades: we now know more about the topology and f
%U http://www.biomedcentral.com/1752-0509/3/51