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Cell Biology I: Kees Jalink

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Kees Jalink, Ph.D.Group Leader

About Kees Jalink

Biophysics of Cell Signaling

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.

Co-workers

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Jeffrey Klarenbeek

Technician

Experience

I studied chemistry, and now hold a supportive position as biochemist in the Jalink lab. I have a keen interest in development of new FRET sensors and also study migration of cancer cells.

I support the students, post-docs and PhD students in the group in any possible way and am involved in many of the running projects, e.g. elucidating the mechanism underlying the internalization of Connexin43 and investigating the role of the channel-kinase TRPM7 in actin remodeling and migration.

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Daniela Leytón Puig

Ph.D. student

Experience

I studied Bio Medicine at the Complutense university in Madrid and got a master´s degree in Molecular Biotechnology at the university of Barcelona, in Spain. I have been working at the NKI as a PhD student in the group of Kees Jalink since December, 2011 mainly on the set-up and application of super-resolution microscopy for biologically challenging samples.

My main research involves the Epithelial Growth Factor Receptor (EGFR) and its targeting for cancer therapy; and the role of a group of proteins in the formation of invadopodia.

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Bram van den Broek

Postdoctoral fellow (Operator high-content confocal screening microscope)

Experience

I am a physicist who has specialized in single-molecule biophysics (PhD) and cellular biophysics (postdoc), with an emphasis on microscopy technique development (including optical tweezers, multifocal 2-photon microscopy, 3D tracking).
 
At the NKI I have a supportive role. In the Jalink lab I focus on developing and maintaining various advanced microscopy and related techniques. Additionally I construct image analysis tools that aid cell biologists to quantify and interpret their data.
 
I am also the contact person for high-resolution confocal high-content screening at the NKI. And I' am working as Operator high-content confocal screening microscope.

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Research updates View All Updates

  • Student Positions - Jalink Lab

     

    7-9 months rotation for master student biology/biomedics/biotechnology at the division of Cell Biology, NKI/AvL, Amsterdam

    From meters to nanometers: Using super resolution imaging to visualize condensed DNA

    When cells divide, it is crucial that the two newly formed daughter cells harbour the exact same genetic material as their mother cell. It is quite a challenge for dividing cells to separate the several-meters long DNA threads without any errors. To achieve this, cells condense their long threads of DNA into short and compact structures that are only few microns in length. This condensation is essential for faithful segregation of DNA but the responsible mechanism(s) are still a big mystery.

    Condensin is an ATPase enzyme that is known to drive the DNA condensation process. The condensin complex consists of five proteins, which together form a gigantic ring-shaped structure that can entrap DNA threads. One model of how condensin confers condensation is by forming and stabilizing long DNA loops inside its ring, thereby bringing distant parts of the chromosome closely together. Through the formation of many consecutive loops, DNA threads would thus become condensed. In this project we aim to visualize DNA and condensin by optical super resolution (SR) microscopy https://www.nobelprize.org/nobel_prizes/chemistry/laureates/2014/press.html

    In SR microscopy the diffraction limit which hampers conventional fluorescence microscopy is circumvented and thereby a resolution up to ~10 nm can be achieved. The first goal is to optimize SR microscopy of DNA and condensin in fixed cells. We will then study how condensed DNA is shaped and the localization of condensin on condensed DNA. We will make use of a number of different condensin variants that either impair or enhance the condensation process. Comparing those different variants of condensin by super resolution might provide valuable insights into how DNA condenses.

    In this project, the groups of Dr B. Rowland and Prof. Dr. K. Jalink, both at the division of Cell Biology, team up. Techniques used include: cell culture / transfections / confocal microscopy / SR microscopy / computer image analysis.

    For information, contact:
    Dr. Ahmed Elbatsh, tel: 020 512 2095, a.elbatsh@nki.nl
    Prof. Dr. Kees Jalink, tel: 020 512 1933, k.jalink@nki.nl

 
 

Recent publications View All Publications

  • Cholesterol and ORP1L-mediated ER contact sites control autophagosome transport and fusion with the endocytic pathway

    Nat Commun. 2016 Jun 10;7:11808

    Wijdeven RH, Janssen H, Nahidiazar L, Janssen L, Jalink K, berlin I, Neefjes J

    Link to Pubmed
  • Beyond ion-conduction: Channel-dependent and -independent roles of TRP channels during development and tissue homeostasis

    Biochim Biophys Acta. 2016 Jun;1863(6 Pt B):1436-46

    Vrenken KS, Jalink K, van Leeuwen FN, Middelbeek J

    Link to Pubmed
 

Contact

  • Office manager

    Mariet van den Berg

  • E-mail

    ma.vd.berg@nki.nl

  • Telephone Number

    +31 20 512 9184

Van den Berg, Mariet

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