"From the molecule to the neurosurgeon", Prof. Thomas Jovin

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Thomas M. Jovin , Donna J. Arndt-Jovin, Michelle G. Botelho, Wouter Caarls, Guy Hagen, Anthony de Vries Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry, 37077 Göttingen, Germany

Contents

[edit] Abstrat

Quantum dots (QDs) are colloidal inorganic semiconductor nanocrystals composed typically of a CdSe, CdS or CdTe core and a ZnS shell. There are many advantages in the use of QDs as fluorophores: they can be excited over a broad spectral range and they have narrow emission bands that can be tuned from ultraviolet to infrared by adjusting size and composition. Their bright emission fluorescence and resistance to photobleaching make QDs ideal for single-particle detection and permit imaging over prolonged time periods. Because of these advantages, QDs are finding increasing use in in vivo and in vitro studies, particularly in combination with expression probes and advanced microscopy techniques. Activation of the erbB receptor tyrosine kinases (erbB1-4) induced by the extracellular binding of peptide ligands triggers signaling cascades responsible for cellular motility, cell division, and differentiation. We have genetically tagged the ErbB proteins with fluorescent proteins and/or the acyl carrier protein (ACP) sequence. QDs have been targeted to receptors on the external cell surface through the growth factor receptor, EGF , or by covalently linking to the ACP tag allowing the visualization in living cells of individual receptors, the diffusion of which has been determined on different cell types. We have also used them to detect dimerization and activation of the transmembrane erbB proteins upon ligand binding. These reagents have revealed a new mode of retrograde transport of the activated receptor from cellular extensions (filopodia) to the surface of the cell [1,2; unpub. data]. The process is linked to treadmilling of actin filaments, which may occur on the cell body as well as on the filopodia. Recently, we have extended such studies by the use of magnetic nanoparticles. Results from basic research studies of erbB tyrosine kinase receptors have led to the application of QD probes in delineating glioblastoma tumors, a collaboration with neurosurgeons in Göttingen. The objective of these studies is to facilitate the localization of tumor margins during surgery, thereby facilitating the accurate resection of the tumor (including of small cellular foci) with minimal loss of normal brain tissue. Similar probes have also helped to elucidate a new role for the amyloid precursor protein (APP) in the maintenance and progression of of malignant melanoma [3]. The detection and tracking of single molecules, and the elucidation of fast, short-lived physiological processes, such as dimerization of proteins on the surface of live cells, require rapid and sensitive optical sectioning microscopy. For that purpose, we have devised new spectroscopic techniques (e.g. FRET -based) as well as an instrument denoted as the Programmable Array Microscope (PAM) [4,5]. The PAM utilizes a spatial light modulator (SLM) placed at the primary image plane to construct patterns of conjugate (as well as non-conjugate) illumination and detection. By integrating over a number of such patterns (points, lines, psuedorandom), an optically sectioned image is generated in the short periods required for live cell studies.

1. D.S. Lidke, P. Nagy, R. Heintzmann, D.J. Arndt-Jovin, J.N. Post, H.E. Grecco, E.A. Jares-Erijman and T.M. Jovin, Nat. Biotechnol. 22 (2004), p. 198. 2. D.S. Lidke, K.A. Lidke, B. Rieger, T.M. Jovin and D.J. Arndt-Jovin, J. Cell Biol. 170 (2005), p. 619. 3. M. Gralle Botelho, X. Wang, D.J. Arndt-Jovin, D. Becker, T.M. Jovin, submitted for publication. 4. G.M. Hagen, W. Caarls, M. Thomas, A. Hill, K.A. Lidke, B. Rieger, C. Fritsche, B. van Geest, T.M. Jovin and D.J. Arndt-Jovin, Proc. SPIE 6441 (2007), p. S1. 5. G.M. Hagen et al. in “Single Molecule Dynamics”, eds. Ishii, Y. & Yanagida, T. (Wiley, Orlando) (2008), in press.


[edit] Short Biography

  • B.S. California Institute of Technology, Pasadena, CA (1960)
  • M.D. Johns Hopkins Medical School, Baltimore, MD (1964)
  • Scientific Member, Max Planck Society (1969)
  • Department Head, Molecular Biology Dept., MPIbpc (1971)

[edit] Professional Memberships

  • Member, European Molecular Biology Association (EMBO)
  • Member, Iberoamerican Molecular Biology Association (IMBO)

[edit] Awards and Honorary Degrees

  • Honorary Professor, Universidad de Buenos Aires, Argentina (1989)
  • Dr. h.c., University Medical School of Debrecen, Hungary (1996)
  • Dr. h.c., Universitair Center Diepenbek, Belgium (1998)
  • Carl Zeiss Ernst Abbe Lecturer (2001)
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