Prestigious Vici grant for Joost Hoenderop and Ronald Roepman

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Joost Hoenderop and Ronald Roepman have been awarded a NWO Vici grant of 1,5 M€ each; one of the largest personal scientific awards in the Netherlands!

Professor Joost Hoenderop (Dept. of Physiology) has been awarded his proposal entitled: "Majestic magnesium: a molecular gateway to new therapies".

Hoenderop, JoostMagnesium (Mg2+) is of central importance for a wide variety of physiological processes in our body, including intracellular signaling, neuronal excitability, muscle contraction, bone formation and it acts as essential cofactor in numerous enzymatic reactions. The overall Mg2+ balance is tightly regulated by the concerted actions of the intestine, bones and kidneys, which keep plasma Mg2+ levels within a narrow physiological range. Deficiencies in the Mg2+ balance result in serious health problems including tetany, ataxia, seizures, neuromuscular abnormalities and cardiac arrhythmias that can lead to sudden death. Mg2+-related disorders can be inherited in which magnesiotropic genes have been mutated or acquired in which drugs or environmental circumstances severely affect the Mg2+ status. Over the last years my group identified the first magnesiotropic genes but the functionomics of several transporters remains unclear. This multidisciplinary project is aimed at studying rare and acquired disorders to unravel (patho)physiological Mg2+-related processes in the human body. Elucidation of the genetic etiology and the underlying pathophysiology, will greatly increase our understanding of the normal physiology of body Mg2+ handling. Ultimately this will lead to better therapy for patients with Mg2+ deficiencies and to prevent long-term complications of chronic Mg2+ disturbances.

Dr. Ronald Roepman (Dept. of Human Genetics) has been awarded his proposal entitled: "Deciphering ciliary signal transduction".

Roepman, RonaldCilia are hair- or tail-like protrusions of the plasma membrane that marks the exterior of the cell. They have been known for centuries, ever since the Dutch scientist Antoni van Leeuwenhoek discovered them with his first microscopes. Later, they were identified in nearly every tissue of the human body, often as a single, immotile or primary cilium per cell. These were long considered as evolutionary remnants, having lost their motility and thus their role in fluid propulsion.

Only in the last decade it became clear that the opposite is the case. Being positioned at the surface, the cilium acts as the cell's antenna, receiving essential extracellular information and transducing that to the right subcellular structure for a response: ciliary signal transduction. Disruption of this function can lead to a broad spectrum of hereditary disorders, potentially affecting nearly every organ in our body: the ciliopathies.

It is largely unknown how the cilium organizes these signal transduction events, especially what proteins are involved, and how the ciliary signals are transfered out of the cilium to the specific subcellular compartments. By elucidating this, Ronald Roepman expects to gain a detailed picture of which processes are controlled by cilia and how that is achieved, how a disrupted cilium function leads to a ciliopathy, and eventually which drugs can antagonize this disruption, and thus be used to treat these dramatic diseases.

For more information (in Dutch) see: http://www.nwo.nl/actueel/nieuws/2013/miljoenenpremies-naar-32-toponderzoekers.html

 

 


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