Title: Regulatory mechanisms in biological systems in response to compound environmental changes
Funder: Engineering and Physical Sciences Research Council

Abstract: All actions in biological systems are controlled by extensive regulatory networks within and across different levels, such as cellular, physiological, and individual levels. In this sense, control is the manifestation of any life activity, and its revelation is the key to understanding the mystery of life . Here, control is considered to be a physical-components-based mechanism used by biological organisms to attain their objectives. The ultimate aim of the proposed research is to establish a theory for biological control, to (re)capture the various phenomena in biological systems from the viewpoint of control, and to reveal the design principles that are common to biological control systems across different levels and different species.Although control has been an essential theme in the field of life sciences for a long time, research on control in life sciences has been developed independently at different levels: homeostasis at the physiological level, cybernetics at the species level, and regulatory biology and more recently systems biology at the cellular level. However, the fact that complex biological regulatory mechanisms have developed through evolution from primitive single-cell organisms with strictly constrained cellular resources suggests that the essential components of regulatory mechanisms might have common features across different levels. I believe that it is thus natural to search for a unified theory of biological control that can provide a viewpoint that will improve our essential understanding of biological regulations in the new era of life sciences. Such a theory is not only crucial in academia but also necessary for accurate assessment and effective treatment of dynamically changing disease states. It should provide essential information for practical clinical treatment towards next-generation healthcare.One of the salient features of biological control systems, compared to man-made ones, is their ability to change their structures and/or functions to match the situation. This plasticity enables biological organisms to adapt to almost any environmental change and to take appropriate actions. Plasticity appears, depending on the time scale, as evolution, differentiation, or learning. Whereas man-made systems use specific regulatory mechanisms corresponding to the environmental change, biological systems, with their limited resources, have to exhibit a broad range of flexible actions with one regulatory mechanism in response to a wide variety of environmental changes. The proposed research focuses on this characteristic and aims to reveal the essential elements of biological control across different levels that attain such plasticity by developing a mathematical theory that can explain the underlying mechanisms of biological control. In particular, I will pursue the underlying regulatory mechanisms from the viewpoint of compound control, the basic idea of which is that complex biological regulations result from spatial and temporal combinations of simple homogeneous computational media, such as interactions among different molecules for cellular control and neuron firings for cerebral control, corresponding to various compound environmental changes. I will focus on the development of a theoretical basis for biological control at the cellular level first and then that in immune systems, which use both cellular- and physiological-level controls. The basic studies at the cellular level on genetic and metabolic systems, together with applied studies on immune systems, both based on the idea of compound control, should reveal the essential design principles of biological control systems


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: GENERIC HEALTH RELEVANCE;INFLAMMATORY AND IMMUNE SYSTEM