The Groningen Research Institute of Pharmacy (GRIP) of the Faculty of Science and Engineering has a position for a PhD candidate in the department of molecular pharmacology. The project is funded by a grant from the Netherlands Organization for Scientific Research (NWO), panel Sciences (ENW).
Human physiology is crucially dependent on interactions between nerves of the peripheral autonomous nervous system and effector organs. These nerves control organ function and allow coordination of physiological events between different organ systems. This is true for all internal organs, e.g. the lungs (focus of this project), heart, kidneys, gastrointestinal and urogenital tracts etc., but equally true for skeletal muscle functions, immunological functions (innervation of the lymph nodes and spleen), and regenerative functions (neural control of bone marrow stem cells).
Dysfunctional communication between nerves and their effector organs contributes to and often even underpins diseases in the aforementioned effector organs such as asthma, COPD, hypertension, Crohn’s disease and many others. Chronic inflammation in these diseases drives plasticity of the nerves, contributing to increased neuronal density and altered neuronal function. Although it is increasingly clear that such neuroplasticity sustains pathological responses including chronic inflammation, pain and itch, surprisingly little is known as to the mechanisms that control neuroplasticity in the peripheral nervous system.
Mast cells play a major role in interacting with neurons, controlling each other’s activation state through secreted products such as histamine, serotonin and neurokinins. How such interactions control chronic neuroplasticity of the neural network in the lung is poorly described. Here, we will use a novel microfluidic neuron-on-chip system equipped with stem-cell derived human sensory and cholinergic neurons to describe these functional interactions. The goals of this project are to advance human physiology modelling technology for neuro-effector interactions, and to provide a roadmap for mast cell-neuron interactions that will be used for target discovery of novel anti-inflammatory drugs.
The prospective starting date will be January 1st, 2022.
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