Circadian regulation of tanycytes: its role in the regulation of rhythmic physiology in health and in circadian misalignment

The suprachiasmatic nucleus (SCN) of the brain, our internal clock, synchronizes physiology to the Earths rotation using signals from the environment such as light and food intake.

However, in industrialized cities, these same signals at wrong times uncouple the internal clock from the environment, leading to circadian misalignment, such as in night and shift workers, who have elevated risks of developing obesity and metabolic syndrome. Nevertheless, effective measures to delay or limit health costs for these people are yet to come.

Recently, I described novel vasopressinergic SCN neuronal (SCNAVP) fibers in the vicinity of non-neuronal hypothalamic cells known as tanycytes that have the ability to sense and transport metabolic cues.

Whether the sensor and transporter functions of tanycytes are regulated in a circadian manner by the SCN, and whether this regulation plays a role in the development of metabolic impairments during circadian misalignment, are unknown.

Thus, in the Circanycyte project, we will seek to 1) determine how SCNAVP neurons control tanycytic function, 2) explore the role of SCNAVP neuron-tanycyte communication in circadian alignment and metabolic fitness, and 3) determine the contribution of SCNAVP neuron-tanycyte miscommunication to the development of metabolic syndrome during circadian misalignment.

To accomplish these aims, I will undergo training in cutting-edge technologies (e.g.

Ca2+ in vivo imaging of tanycytes, with simultaneous optogenetic manipulations), while I exercise my leadership and management skills by working in a top laboratory, using the experience as a launching pad for international collaborations in frontier science in the EU.

My original angle of research, hypothesizing that tanycytes, which extend processes outside the blood-brain barrier, are key targets of the SCN to regulate metabolism, is a strategic choice that promises to uncover new actionable pharmaceutical targets to fight desynchronization-related disorders