Research interest
It has become clear that most, if not all, signal transduction pathways can only be truely understood by knowing them in great detail, that is, by knowing exactly where and when they become activated, how they are deactivated and what the intricacies are of e.g. compartmentalization and cross-talk. Because signaling events involve molecular interactions, it is also clear that a nanometer scale applies. This means that the tools to study signals must yield data with spatial and temporal detail from living cells, preferably from cells that are as much as possible in a natural environment.
In our laboratory, we combine cell biology with live cell imaging and biophysical tools capable of supplying the required spatiotemporal resolution. For example, Fluorescence Resonance Energy Transfer (FRET) is used to dynamically follow molecular interactions with nanometer resolution, and techniques like high-performance Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Cross Correlation Spectroscopy (FCCS) reveal protein-protein associations at a sub-millisecond scale. We build and operate the dedicated equipment for these studies, and we contribute new technological developments and new FRET sensors.
Whereas part of the techniques employed are biophysical, our research interests are very much in cell-biology, including:
- the “channel-kinase” TRPM7, a bifunctional protein that combines a non-selective cation channel and a serine/threonine kinase. TRPM7 regulates cell adhesion and cell spreading and, in turn, it is controlled by several signaling cascades including the Gaq-PLC route. Our working hypothesis is that TRPM7 acts as a mechanosensor that controls the formation of adhesive structures known as podosomes/invadopodia.
- its sibling TRPM6, which serves a role in gut and kidney as gate-watcher of organismal Mg2+ homeostasis. Regulation of TRPM6 is largely unexploited.
- the spatiotemporal control of phosphoinositides such as PIP2 and their role as messenger molecules.
- and several collaborative projects with groups both within and outside the NKI.
Key publications
Ponsioen B, Gloerich M, Ritsma L, Rehmann H, Bos JL, Jalink K. Direct spatial control of Epac1 by cAMP. Mol Cell Biol. 2009 Mar 9. [Epub ahead of print].
Van Zeijl L, Ponsioen B, Giepmans BN, Ariaens A, Postma FR, Várnai P, Balla T, Divecha N, Jalink K, Moolenaar WH. Regulation of connexin43 gap junctional communication by phosphatidylinositol 4,5-bisphosphate. J Cell Biol. 2007 Jun 4;177(5):881-91. Epub 2007 May 29.
Langeslag M, Clark K, Moolenaar WH, van Leeuwen FN, Jalink K. Activation of TRPM7 channels by phospholipase C-coupled receptor agonists. J Biol Chem. 2007 Jan 5;282(1):232-9. Epub 2006 Nov 9.
Clark,K., Langeslag,M., van Leeuwen,B., Ran,L., Ryazanov,A.G., Figdor,C.G., Moolenaar,W.H., Jalink,K., and van Leeuwen,F.N. (2006). TRPM7, a novel regulator of actomyosin contractility and cell adhesion. EMBO J 25, 290-301.
Jalink,K. (2006). Spying on cGMP with FRET. Nat. Methods 3, 11-12.
Langeslag,M., Clark,K., Moolenaar,W.H., van Leeuwen,F.N., and Jalink,K. (2006). Activation of TRPM7 channels by PLC-coupled receptor agonists. J Biol Chem. 282, 232-239.
Danen,E.H., van Rheenen,J., Franken,W., Huveneers,S., Sonneveld,P., Jalink,K., and Sonnenberg,A. (2005). Integrins control motile strategy through a Rho-cofilin pathway. J Cell Biol 169, 515-526.
van Rheenen,J., Achame,E.M., Janssen,H., Calafat,J., and Jalink,K. (2005). PIP2 signaling in lipid domains: a critical re-evaluation. EMBO J 24, 1664-1673.
van Rheenen,J., Langeslag,M., and Jalink,K. (2004). Correcting confocal acquisition to optimize imaging of fluorescence resonance energy transfer by sensitized emission. Biophys J 86, 2517-2529.
Ponsioen,B., Zhao,J., Riedl,J., Zwartkruis,F., van der Krogt,G., Zaccolo,M., Moolenaar,W.H., Bos,J.L., and Jalink,K. (2004). Detecting cAMP-induced Epac activation by fluorescence resonance energy transfer: Epac as a novel cAMP indicator. EMBO Rep. 5, 1176-1180.
More publications by Kees Jalink on PubMed.
Biographic sketch
Kees Jalink studied Biology at the State University of Leiden, The Netherlands. After graduation in 1987 (cum laude) he continued for another year in the group of prof. Dick Ypey to further develop his understanding of electrophysiology and Ca2+ imaging. From 1988 to 1993 he did his PhD (cum laude) in the lab of prof. Wouter Moolenaar where he co-discovered Lysophosphatidic Acid (LPA) as a receptor agonist. From 1993 to 1997 he worked as postdoc in the labs of prof. Charles Zuker and prof. Roger Tsien, both at UCSD in La Jolla, CA. Here he worked on Drosophila phototransduction, again with emphasis on electrophysiology and live-cell fluorescence. From 1997 on, he rejoined the NKI as head of the cell biophysics group in the department of Cell Biology. His group studies cell-biology using a broad mix of cell-biological, molecular and biophysical techniques.
Kees Jalink's long-standing interest in physical techniques, electronics and computer programming have enabled him to establish state-of-the-art equipment for live-cell imaging and biophysical experiments. He is senior advisor to screening- and microscopy companies in the USA, Germany and in the Netherlands.
Co-workers
Daan Visser MSc Graduate student
Jeffrey Klarenbeek PhD Technical staff