This postdoctoral project aims to establish the structural and thermodynamic properties of Ca2+-sensitive domains or proteins that regulate Ca2+ transport across the membrane. Ca2+ ions are crucial in many cellular processes, including neuronal response, muscle contraction, enzyme activity, gene transcription, cell death, proliferation and differentiation. We study specific structural domains/proteins and their interactions that regulate the transport of Ca2+ across the membrane. Specific systems currently involve the Na+/Ca2+ exchanger, a highly ubiquitous ion transporter that constitutes the dominant Ca2+ efflux mechanism in heart and sensory neurons and the TRPV5/6, a Ca2+ channel functionally connected to the exchanger. This project will be approached by conducting advanced high-resolution NMR spectroscopy experiments, yielding information on structure and dynamics on different timescales, in conjunction with other biophysical techniques, such as Isothermal Titration Calorimetry (ITC), yielding information of energetic aspects of the interactions. Together, they serve as a basis for the design and implementation of structurally inspired modifications of function and testing of these concepts with cell-biological assays. This two-year postdoctoral project will be conducted by the Protein Biophysics group of the Institute for Molecules and Materials and will be performed in collaboration with Dr. M. Hilge, Prof. R. Bindels (NCMLS, Nijmegen) and Dr. J. Hoenderop (NCMLS, Nijmegen).
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