Systems Biology

Biological organisms are systems that comprise of multiple, heterogeneous subunits that operate in a well-orchestrated manner. Although extremely complex, phenotypes such as cell division and environmental adaptation can be correlated to discrete changes that lead to a deterministic sequence of information transfer and processing within cells. Such information is encoded and transferred via multiple pathways, in different time-scales, and it is typically processed in parallel, by multi-component networks. Today, it is commonly accepted that a systemic approach based on cross-fertilization of theory and techniques from different disciplines will be essential to unravel the complexity of biological organisms. The integration of knowledge from engineering disciplines, and in particular of control theory to biology, may not only advance our scientific understanding but also lead to technologies that benefit our society. This session will cover recent developments in some of the central theoretical and experimental research themes of systems biology: reverse engineering of networks, properties of network motifs, micromanagers for gene regulation, and modularity in cells.

The first talk will introduce an integrative method that combines multiple types of large-scale molecular data, including genotypic, gene expression, transcription factor binding site, and protein-protein interaction data to reconstruct causal, probabilistic gene networks and predict complex system behavior. The importance of incorporating systematic sources of perturbations to infer causal relationships among genes will be emphasized. The second talk will provide a survey of system-theoretic approaches for dissecting intracellular networks and will introduce the concept of control motifs. While comprising a few relatively simple elements, motifs are often embedded in multi-component coarse-grained networks that exhibit complex behavior, and appear with different frequency as information processing components of transcription, developmental, signal transduction, and neuronal networks. Motifs not only provide a powerful framework for analyzing intracellular networks, but also help bridge the fields of biology and control, allowing tools and approaches from control theory to be applied to biology. The third talk will address current opportunities and issues in the development of microRNA therapeutics. MicroRNAs are regulatory RNAs that control numerous cellular processes. Attracting increasing attention recently, miRNAs are abundant in multicellular organisms and their operation as gene regulatory molecules is actively investigated. Finally, the fourth talk will introduce the concept of modularity and retroactivity in biology. The modularity property guarantees that the input/output behavior of a system does not change when it is connected to other systems, while retroactivity models the change of a module dynamics upon such interconnection. This is especially important in the field of synthetic biology where simple components are built and tested in isolation and then are connected to realize more complicated functionalities. Methods to mathematically quantify retroactivity in transcriptional networks and to attenuate its effect through the design of insulation devices will be presented.