Exploring Tools to Understand Control Mechanisms in Biology
It is increasingly evident that cells and organisms have developed robust strategies to self-maintain their physiological states through regulation of cellular gene expression, metabolism, and cell behaviour. How do organisms achieve this? And will it be possible to engineer or repair control mechanisms, which have lost their robustness and become life-threatening? To do this we need tools that allow us to understand the how the key regulatory mechanisms operate collectively.
The discipline of control-engineering has for many years developed methods to analyse complex networks of regulatory interactions. Such analysis can help us understand homeostatic mechanisms and the workings of homeostatic control loops that are key to robust physiological processes. The study of the relationship between control-engineering concepts, for example integral control, and corresponding molecular mechanisms is a rapidly emerging and highly interdisciplinary field of research which combines computational/ mathematical, kinetic, cybernetic, and molecular biology methods.
The DLN work group on Competence and Infrastructure Networks has recently organized a two-days workshop together with researchers at the University of Stavanger; Peter Ruoff, Tormod Drenstig and Kristian Thorsen, who have for many years worked with the application of control theory to biological systems. The workshop “Control Engineering Concepts in Systems- and Synthetic Biology” was sponsored by the Norwegian Research School in Bioinformatics, Biostatistics and Systems Biology (NORBIS) and Digital Life Norway Research School (DLN RS).
The aim of this workshop was to bring together researchers from different fields to present their developing concepts with respect to robust regulation and modelling. The meeting was held at the Centre of Organelle Research, University of Stavanger, Norway, May 20-22, 2019.
The program was divided into four major sessions, starting with Modeling of biological systems, and principles for control and regulation, and Engineering approaches to biological and biomedical systems during day one, with keynote speakers Brian Ingalls (Univ. Waterloo, CA), Jens Timmer (Univ. Freiburg, GE) and Krishnan (Imperial College of London, UK). Day two covered the topics Modeling biological systems, and learning from models and Model reduction, identifiability, observability and keynote speakers Olivier Bernard (BIOCORE, FR), Hans Stigter (Wageningen Univ., NL) and Jens Timmer. The program also featured many presentations by young researchers in DLN projects such as the DIAP and dCod project and in modelling projects not formally in DLN. Thus, the program covered quite broadly both applications of theory and modelling to delineate underlying homeostatic regulation and information processing in natural and engineered cells, as well as theoretical methods to analyse the structural properties of dynamic systems, model reduction and uncertainty analysis. From the workshop it has become clear that the field of systems biology and synthetic biology has much to gain from established theories and tools in control engineering.
While some years ago there were only a few groups working within this field, it is now a rapidly expanding area of research. The establishment of NORBIS and Digital Life Norway (DLN RS) in 2015 and 2016 by The Research Council of Norway has been a welcome initiative to focus on this highly interdisciplinary research field. The organizers would like to thank NORBIS and DLN RS for their financial support.
By Peter Ruoff and Rune Kleppe