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Dorus Gadella

Abstract

Titel:
The microscopy and bioimaging revolution: seeing is believing.

Abstract:
The green fluorescent protein- and the microscopy revolution have generated an enormous potential for life science research. It is now routinely possible to monitor dynamics of enzyme activity and protein-protein interactions in (single) living cells. Hereby bioimaging adds the time and spatial dimensions to proteomics and genomics. Recently, in fluorescence microscopy, the diffraction limit has been shattered. Instead of the usual optical resolution limit of 0.2 µm, now images of cells have been sharpened up to resolve 10-30 nm structures, approaching the resolution of electron microscopy. Simultaneously, the ultimate detection limit, that of a single molecule in a living cell, is currently routinely achieved. Combined with advanced digital imaging analysis and automation in parallel microscopy approaches has created a huge potential that currently revolutionizes molecular cell biology.

Professional carreer

Dr. Gadella is co-founder/director of the van Leeuwenhoek Centre for Advanced Microscopy (LCAM) and full professor in Molecular Cytology chairing a group of 25-30 scientists at the university of Amsterdam. The LCAM is a joint advanced microscopy centre between the Science Faculty of the University of Amsterdam, the Academic Medical Centre (AMC) and the Netherlands Cancer Institute (NKI-AVL) in Amsterdam. Dr Gadella personally supervises a research team on spatiotemporal cell signaling. His team wants to understand how cells can achieve and maintain a local signal in order to drive morphogenesis, to define new cytoskeletal anchorage or vesicle-docking sites. The focus is on signal flow across and in the plane of the membrane of living mammalian cells. To this end genetic encoded fluorescent biosensors are developed and employed, and the in situ molecular interactions between signaling molecules including phospholipid-second messengers, receptors, G-proteins and downstream targets are analyzed. For these biosensors new superfluorescent proteins have been developed such as SYFP2 (the brightest GFP variant on the planet) and mTurquoise2 (the brightest cyan fluorescent protein known to date). By multiparameter imaging approaches several signaling events are visualized and quantified simultaneously in individual living cells with sub-second temporal and submicron spatial resolution. The in situ cellular imaging research heavily depends on advanced bioimaging. To this end advanced automated microscopy approaches such as fluorescence resonance energy transfer (FRET) microscopy (including bleaching-, spectral-, ratio- and fluorescence lifetime-imaging approaches), fast live cell microscopy (including spinning disk, line-scanning and controlled light exposure confocal microscopy, and total internal reflection microscopy (TIRF)), and photochemical microscopy approaches such as photoactivation, uncaging, fluorescence recovery after photobleaching (FRAP), fluorescence loss in photobleaching microscopy (FLIP), fluorescence correlation spectroscopy (FCS), cross-correlation (FCCS), lifetime-correlation (FCLS) have been implemented developed  and applied to quantifying cell signalling phenomena. Recently, the palette of advanced imaging instrumentation is expanded with superresolution localization microscopy approaches such as SIM, PALM and STORM.

In 2007 prof Gadella was elected president of the Netherlands Society for Microscopy. Recently he has become national coordinator of the NL-BioImaging Advanced Microscopy consortium of 18 collaborating advanced microscopy centres in the Netherlands that connects to the new large EU infrastructure (ESFRI) roadmap Euro-BioImaging that entered the preparatory phase in 2010.

Employment:

  • 2011-present: Director and co-founder of the van Leeuwenhoek Centre for Advanced Microscopy (FNWI-AMC-NKI) in Amsterdam.
  • 2007-2010: President of the Netherlands Society for Microscopy (NvVM).
  • 2004-2011: Director & founder of the Centre for Advanced Microscopy (CAM) at the University of Amsterdam
  • 2001-present: Full professor of Molecular Cytology Swammerdam Institute for Life Science at the Science faculty of the University of Amsterdam.
  • 1999-2001: Assistant professor Molecular Biology, Wageningen University and Research Centre, The Netherlands.
  • 1996-1999: Post-Doctoral Fellow of the Royal Netherlands Academy of Sciences at the Department of Molecular Biology, Wageningen University. The Netherlands.
  • 1994-1996: Post-Doctoral fellow at the Department of Biochemistry of the Wageningen University The Netherlands.
  • 1991-1994: Post-Doctoral fellow at the Max Planck Institute for Biophysical Chemistry, Department of Molecular Biology, Göttingen, Germany
  • 1987-1991: PhD student, Department of Biochemistry, Utrecht University

Awards:

  • 1987: Unilever Research Prize.
  • 1997: FEBS Anniversary Prize of the Gesellschaft für Biologische Chemie, based on "achievements in the field of application of fluorescence lifetime imaging to cell signalling phenomena".