Hierarchical Control Analysis of (dys) Regulation of Microbial Physiology
Research Projects:
Regulation by and of membrane energetics by the H+-ATPase
Versatile regulation of and by membrane linked electron transfer
Regulation of and by DNA supercoiling
Regulation of N2 fixation
Dynamic and intelligent signal transduction
Mathematical biochemistry
Control and regulation through intercellular interactions
With the new research program Hierarchical Control Analysis, the rejuvenated department of Microbial Physiology of the Vrije Universiteit Amsterdam aims at quantitatively elucidating how the functioning of the living cell is managed simultaneously through various regulatory levels. In a broad and general, theoretical and experimental approach, all the at this moment available biomathematical, biochemical, microbiological, and molecular genetic techniques will be exploited. It is also the aim of this program to elucidate how living cells bring about subtle and appropriate responses to changes in their environment by invoking these regulatory mechanisms. More specifically the question is addressed to what extent different regulatory routes are active simultaneously or successively. The model organisms of choice are P. denitrificans, A. caulinodans and E. coli. The approach is quantitative, using molecular genetics and biomathematics. The research program is of general scientific interest because it is the first to recognise the phenomenon that the regulatory network of cells is itself subject to regulation (through regulated gene expression) and is thus an example of a structurally non-linear system. Many of the hitherto unexplained complex properties of prokaryotic cells may become explained in this way and many unsuspectedly complex properties may become recognised and understood. It may help understand the inherent complexity of biology.