Job Radboud University Nijmegen Medical Centre (RUN MC) - PhD student (biology, life sciences, chemistry)

Within the departments of Physiology of the Radboud University Nijmegen Medical Centre and Organic Chemistry of the Radboud University Nijmegen we are seeking a PhD student for a collaborative research project.

 Maintenance of blood calcium (Ca2+) concentrations within a tight normal range is essential for ample physiological functions. The kidney is critically important in this process, where Ca2+ that enters the glomerular filtrate is reabsorbed from the tubular system back into blood. We made two important discoveries in completing the molecular details of the renal Ca2+ homeostasis. First, we identified the epithelial Ca2+ channel (TRPV5) that is the target for hormonal control of Ca2+ flux from the urine space to the blood. Second, our studies unveiled a novel concept of regulation in which the extracellular exposed N-glycan of TRPV5 is essential to regulate channel activity. The urinary anti-aging hormone klotho is active as a β-glucuronidase and probably sialidase to cleave sugars from the N-glycan on TRPV5 resulting in enhanced channel activity (Science 310:490-493,2005). Glycoscience, the study of carbohydrates on the surface of proteins, is particularly relevant in the post-genomic era, as glycosylation is one of the main post-translational events. The importance of glycosylation in regulation of protein activity, cell signaling and development is only now becoming fully appreciated. This project aims to unravel the molecular mechanisms by which klotho and other glycolytic enzymes control the epithelial Ca2+ channel and therefore renal Ca2+ handling.

This collaborative project opens for the first time a way to study the functional regulation of TRPV5 by extracellular modification of the fused glycan. The recent expansion of glycobiology has provided many new, imaginative and efficient techniques that present further insight into the function and regulation of plasma membrane proteins like ion channels. Besides the implications of understanding TRPV5 function and the pathophysiology of Ca2+-related disorders, this new concept of channel regulation and the established experimental protocols will be applicable to the functional role of glycan structures on plasma membrane proteins in general.

MSc in molecular life sciences or chemistry with interest in life sciences

• Independent and well-structured working style
• Strong motivation to succeed in scientific research
• Well-developed social skills directed to work in a team

• Temporary, 4 years
• 36 hrs per week
• Salary level  10A: maximal € 2673 gross per month

Nijmegen http://www.umcn.nl/ UMC St Radboud

Radboud University Nijmegen Medical Centre (RUN MC) is a leading academic centre for medical science, education and health care. Knowledge forms the heart of our organisation, connecting research, education and patient care. Over 8.500 staff and 3.000 students are committed and ambitious to contribute to the future of health care and medical science.

Driven by knowledge, empowered by people.

The department of Physiology provides an international and stimulating working environment for its ~50 employees and is an exciting place to perform basic research, translational and clinical medicine, and enjoy teaching. The department encompasses complementary research groups whose interests range from cardiovascular adaptations to inactivity, molecular regulation of ion transport processes in the kidney to the study of osmoregulation in the body. Working collaboratively within the department, we use our expertise to investigate how molecules, cells, organisms and humans function and how we might modulate their physiology to ultimately improve health in the patient.

 The department consists of the research groups Integrative Physiology, Ion Transport and Osmoregulation and is part of the Radboud University Nijmegen Medical Centre (RUNMC) and the Nijmegen Centre for Molecular Life Sciences (NCMLS), a leading multidisciplinary research school within the domain of molecular mechanisms of disease and particularly in the fields of molecular medicine, cell biology and translational research.

 This vacancy belongs to the Ion Transport group.

Dr. J. Hoenderop, full professor, J.Hoenderop@fysiol.umcn.nl, +31 24 3610580

Dr. F. van Delft, ass. professor, f.vandelft@science.ru.nl, +31 24 3652373