The Ciliary Logistic Network in health and disease.

• Applicant: Dr. Regina J. Faubel
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Anatomy and Physiology ; Cell Biology
• Term: from 2018 to 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 405373729

Cerebrospinal fluid fills the ventricular system of the brain and contains hundreds of substances of diverse functions ranging from nurishing, protective, or toxic effects to regulation of physiology and behavior. Humoral signals found in cerebrospinal fluid include hormones and peptides that regulate sleep/wakefulness, circadian rhythm, food uptake, and emotional behavior. The sites of secretion and sites of action have been extensively studied but the transport paths through the ventricular system remain largely unknown. Cilia are rod-shaped, cellular protrusions that reach into the ventricular volume and exert a swimming-like movement to generate directional flow. Genetic mutation can cause immotility of cilia leading to hydrocephalus, a condition of water accumulation in the brain that causes increased intracranial pressure and swelling. Whereas it was previously believed that these cilia beat in a uniform direction to facilitate outflow from the ventricles, our recent discovery of the Ciliary Logistic Network revealed that cilia actively generate flow channels and barriers and orchestrate distribution of molecules within the ventricular system. This network meets the characteristics of a precise and efficient transport system. We identified genetic mutations in mice that lead to changes of substance distribution in the absence of hydrocephalus and we will assess how humoral communication and clearance of the tissue surface are affected. Furthermore, we identified several external and endogenous cues that affect cilia-beating and we will assess their potential to restore the Ciliary Logistic Network. This research has clinical implication as typical symptoms of patients with hydrocephalus are thought to be result of increased pressure. Showing that those symptoms are a direct consequence of disregulated substance distributions will open doors for novel treatment approaches.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Cecilia W. Lo