The Board of NWO Domain Science has awarded in the NWO Open Competition Domain Science, Jenny van der Wijst, theme Renal Disorders, the ENW KLEIN grant of 350,000 Euro. KLEIN grants offer researchers the possibility to realize curiosity-driven, fundamental research and elaborate creative and risky ideas.
The project “Calmodulation of the epithelial calcium channels TRPV5 and TRPV6: Untangle a dual-faced mechanism” is centered on how the calcium binding protein calmodulin conditions the ion channels’ physiology by exploiting our recently obtained structural data of the TRPV5-calmodulin complex. The TRPV5 and TRPV6 channels form a specific category within the large TRP family of ion channels as they are selectively permeable for calcium ions and play important roles in systemic calcium homeostasis. Using a combination of electrophysiology and advanced fluorescence microscopy, we aim to decipher the calcium-dependency of the TRPV5/6-calmodulin interaction and connect this to changes in channel activity, to provide a so-called ‘calmodulation’ model for these calcium-selective TRP channels.
Outcomes of this project will advance our understanding of the molecular machinery controlling calcium homeostasis. Moreover, it may open up studies for other TRP family members, which is highly relevant to move towards the complete comprehension of TRP channel (patho)physiology.
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