Regulatory mechanisms in biological systems in response to compound environmental changes

生物系统中的所有活动都受到不同层次内和不同层次之间广泛的调控网络的控制，如细胞、生理和个体水平。从这个意义上说，控制是任何生命活动的表现，它的揭示是理解生命之谜的关键。在这里，控制被认为是生物有机体为实现其目标而使用的一种基于物理组件的机制。这项研究的最终目的是建立生物控制理论，从控制的角度捕捉生物系统中的各种现象，并揭示不同层次和不同物种的生物控制系统共同的设计原则。尽管控制长期以来一直是生命科学领域的一个基本主题，但生命科学中的控制研究一直在不同的水平上独立发展：生理水平的动态平衡，物种水平的控制论，调节生物学和最近在细胞水平的系统生物学。然而，复杂的生物调控机制是从细胞资源受到严格限制的原始单细胞生物体进化而来的，这一事实表明，调控机制的基本组成部分可能在不同的水平上具有共同的特征。因此，我认为，寻找一种统一的生物防治理论是很自然的，它可以提供一种观点，提高我们对生命科学新时代生物调控的基本理解。这样的理论不仅在学术界至关重要，而且对于准确评估和有效治疗动态变化的疾病状态也是必要的。它应该为迈向下一代医疗保健的实际临床治疗提供必要的信息。与人工控制系统相比，生物控制系统的显著特征之一是它们能够改变其结构和/或功能以适应情况。这种可塑性使生物有机体能够适应几乎任何环境变化并采取适当的行动。可塑性的出现取决于时间尺度，表现为进化、分化或学习。人造系统使用与环境变化相对应的特定调节机制，而生物系统由于其有限的资源，必须表现出广泛的灵活行动，通过一个调节机制来应对各种各样的环境变化。这项拟议的研究着眼于这一特点，旨在通过发展一种能够解释生物防治的潜在机制的数学理论，揭示不同水平上实现这种可塑性的生物防治的基本要素。特别是，我将从复合控制的角度来探讨潜在的调控机制，其基本思想是，复杂的生物调节是简单的同质计算介质在空间和时间上的组合，例如不同分子之间的相互作用，用于细胞控制和神经元的激活，用于大脑控制，对应于各种复合环境的变化。我将首先关注细胞水平的生物防治的理论基础的发展，然后是免疫系统的生物防治，免疫系统同时使用细胞和生理水平的控制。在细胞水平上对遗传和代谢系统的基础研究，以及对免疫系统的应用研究，都是基于复合控制的思想，应该揭示生物防治系统的基本设计原则。

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.