The importance of sensory systems over our homeostasis and quality of life.

Sensory functions, such as vision, hearing, touch, taste, smell, and balance are essential to maintain our good quality of life, as external stimuli have to be input to our body system which has to appropriately respond to environmental contexts. During the perception of external stimuli, sense organs work as transducers; various physical stimuli are converted into electronic signals though receptor organs and/or receptor cells, which are transmitted to brain via peripheral nervous system. Those signals are integrated and interpretated by the central nervous system, leading to provide critical directions to maintain homeostasis, including sleep, metabolism, blood circulation, and various hormone levels. In addition to maintaining homeostasis, higher brain functions such as sensory perception, cognition, emotion, and learning are also highly depends on those integrated/interpretated sense signals.

Research targets relevant to sensory systems for delivering better quality of life.

Reflecting their importance, dysfunctional conditions in sense organs bring severe complications at various levels; however, available cures and drugs for disorders in sense organs are currently quite limited. For example, current our knowledge is largely insufficient to prevent diseases related sense organs and it is almost impossible to rebuild lost senses, or to provide radical treatments. This is mainly due to the lack of its pathological understanding; moreover, the lack of comprehensive understanding of the mechanisms that enable to sensory functions to work. Thus, fundamental understanding of the mechanisms that consist sensory functions is undoubtfully necessary to deliver the sufficient cure for sensory faults.

In order to provide sufficient cure for diseases related to sensory systems, it is undoubtfully important to expand our insight into each sensory system; moreover, there are pressing needs to decipher the integration of sensory systems into our whole-body system. As mentioned above, input from sensory systems are tightly integrated into various biological functions including the mechanisms that maintain homeostasis, physiological functions, and physical exertions. For example, on an empirical basis, we knew that our actual senses were indeed consist of a couple of senses; our appetite and intake of food were sometimes affected by the foods' taste, smell, and texture. Therefore, one could argue that our senses are indeed multimodal and investigations on such integration of sensory system into various other biological functions (via central or peripheral nervous system) have to be more extensively focused. Such approaches would facilitate a strong foundation for a variety of treatment strategies: to control the sensory functions, to control the brain and physiological functions via integrated sensory systems, and to cure various diseases related to sensory systems.

Here we propose following three research targets to deliver higher quality of life via providing a series of treatment strategies and knowledge foundation that contribute to improving the health and wellbeing of people.

Target 1: To build a knowledge foundation in the mechanisms of sensory systems: from the receptors to perception.

• To gain a comprehensive view of the relationship between ligands and receptors in chemosensory systems.
• To strengthen our insight into the mechanisms where external stimuli are transduced, precepted, and processed: from the sensory organs to central nervous system via peripheral nervous system.
• To understand the mechanisms that maintain the homeostasis related to sensory systems.

Target 2: To decipher the integrated communications between sensory systems and neurological and physiological functions via brain.

• To determine the influence from sensory systems on other biological functions including central nervous systems, various physiological status, and diseases.
• To determine the effects of various diseases such as cardiovascular diseases, diseases related to metabolism, cancer, on the sensory systems.
• To uncover the functions of taste and olfactory receptors located outside of the sensory organs.
• To discover the unknown sharing component between each sensory system.

Target 3: To build a technological foundation which could lead the manipulation of sensory systems and beyond. Followings are the examples of expected new technological developments:

• New imaging methods which can visualise the activities of peripheral nervous system with high resolution in a wide area.
• New live data acquisition systems which enables to measure the activities of receptors and peripheral nervous system
• Technologies which enables to estimate the responses to external stimuli at the levels of behaviour or nervous activities.
• Technologies that reproduce the integrated sensory systems activities, including with the applications of sensory receptors, organoids, and organ on chips.
• Methods to quantify the senses (pain, smell, taste).
• Technologies and devices that could manipulate the integrated sensory systems, which might work internally or externally.

The way to maximise the research capacity in the integrated sensory systems. In order to decipher, to cure and to control the integrated sensory systems, a good coordination across a wide range of research disciplines is crucial. Relevant disciplines are: in addition to medicine and bioscience, engineering (material engineering and electric engineering), informatics, mathematics, and chemistry. To foster the maximum capability of research, laboratories related to such disciplines have to be well coordinated to establish a virtually networked research institute. Under a courageous leadership, research technologies such as nervous manipulation, imaging, and data analysis could efficiently be shared in the virtual institute. Moreover, research data would be shared to facilitate further understanding or to promote translational researches. Depending on the research progress and phases, the coordination in the virtual institute should iv Center for Research and Development Strategy, Japan Science and Technology Agency CRDS-FY2021-SP-05 STRATEGIC PROPOSAL Deciphering the sensory systems: from its comprehensive understanding to developing the core technologies for innovative applications be flexibly adapted to maximise the research capacity.

Possible further development.

Within a couple of decades, research related to the integrated sensory systems would be well coordinated with the research field of organ crosstalk and neuroscience. Such cross disciplinary research would reveal that our sense is highly multi- and cross-modal which is tightly tangled with other sensory systems or factors (organs). In the light of such complexity, development of research technologies that enable to gain desired effects and on-target manipulation should be essential. In order to build up such technologies, following two research targets should be in mind:

• To determine the relationship between the stimuli and their corresponding peripheral nervous system at the one neuron level.
• To develop technologies to manipulate the peripheral nervous system at the one neuron level, either in vivo or in vitro.

In order to harness the understanding of sensory systems to the maintenance of homeostasis, a possible much ambitious future project of "peripheral nervous system atlas" should be discussed.