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International Research Experience

Program Introduction - Apply Online here

The goal of CBST’s International Research Experience in Biophotonics is to establish an active student exchange program with international partner institutions. 

Following the significant interest expressed by CBST students, the NSF Center for Biophotonics Science & Technology (CBST) was awarded supplemental funds from the National Science Foundation (NSF) to establish a UNIQUE international research experience program in Biophotonics. Cooperating with CBST are partner institutions in Asia, Canada, and Europe. 

Initial collaborations will be started with (see descriptions below): 
Prof. Chien Chou, National Yang Ming University, Taiwan, on improving surface plasmon resonance (SPR) detection of molecular events 
Prof. CH Lin, National Yang Ming University, and Prof. DP Tsai, National Taiwan University, Taiwan, on cellular functional diagnostics by near-field optics and applications of the Gene Gun 
Prof. Arthur Chiou, National Yang Ming University, Taiwan, on intracellular measurements of molecular forces
Prof. Brian Wilson, Toronto University, Canada, on novel approaches to photodynamic therapy 
Prof. Markus Sauer, University of Bielefeld, Germany, on fluorescence quenching by amino and nucleic acids
Profs. Bert Hecht and Dieter Pohl, University of Basel, Switzerland, on Nano-Biophotonics.
Prof. Alfred Meixner, University of Tuebingen, Germany on single molecule spectroscopy
This exchange program will enable CBST students to have access to the unique tools and skills available at these international partner institutions.  Conversely, CSBT will host students from our partnering institutions to build a robust and active international “research exchange program”.  This program will have mutual benefits to all partners and is expected to significantly advance the field. Biophotonics is uniquely suited for this exchange, because it relies heavily on collaborations between Biology, Medicine, Engineering, Chemistry, and Physics.

Apply for the program online here (application accepted on rolling basis - first set will be reviewed June 25, 2006).

Potential Location Descriptions

Partner institution: University of Tuebingen, Germany

Prof. Alfred Meixner and his group at the University of Tuebingen, Germany, are internationally leading in the field of single molecule spectroscopy at low temperatures. Their main expertise is in fluorescence and Raman spectroscopy of organic molecules and macromolecules. Their expertise in conducting experiments at temperatures near 1K enables them to freeze out vibational modes and arrest photo bleaching to obtain information from individual macromolecules at high spatial and spectral resolution over extended periods of time.

See their webpage for more information:

The city of Tuebingen is in situated in the middle of Europe, in the South of Germany, close to the Swiss border and close to Munich. Tuebingen is one of Europe’s oldest university towns with a long-standing history that hasuced a large number of Nobel laureates, such as Hans Bethe (later at Cornell), Ferdinand Braun, Hermann Hesse.

Recent review articles from the Meixner group:
"Microcavity-controlled single-molecule fluorescence" 
M. Steiner, F. Schleifenbaum , C. Stupperich, A. V. Failla , A. Hartschuh , A. J. Meixner Chem. Phys. Chem. 6 (2005), 1-8.
"Exciton dynamics in individual single-walled carbon nanotubes" 
A. Hagen, M. Steiner, M. B. Raschke, C. Lienau, T. Hertel, H. Qian, A. J. Meixner, A. Hartschuh (2005).
"Near-field Raman microscopy" 
N. Anderson, A. Hartschuh, L. Novotny (2005).
"Imaging of tautomerism in a single molecule" 
H. Piwon´ ski, C. Stupperich, A. Hartschuh, J. Sepio, A. Meixner, J. Waluk J. Am. Chem. Soc. 127 (2005), 5302-5303.

Partner institution: University of Basel, Switzerland

Prof. Bert Hecht and Prof. Dieter Pohl are leading in near-field optical microscopy and spectroscopy of resonant optical structures and biomolecules. Their most recent work revolves around tip-enhanced spectroscopy, where the sharp (~ 5-10 nm) tip of a scanning probe microscope serves as a local means to enhance optical contrast of biomolecules on a surface. These systems lend themselves well to the study of surface-bound or supported macromolecules, such as lipid bilayers, proteins in bilayers, and cell membranes. 

See their webpage for more information:

The city of Basel is in situated in the middle of Europe, in the knee of the river Rhine right at the border to France and Germany. It is a picturesque city with a livid inner city with many buildings sti ll standing from the medieval ages. Basel is headquarters to some of Europe’s largest pharmaceutical companies, such as Roche and Novartis. 

Recent publications:

Aperture scanning near-field optical microscopy and spectroscopy of single terrylene molecules at 1.8 K
,  J. Y. P. Butter and B. Hecht,
  Nanotechnology 17 1547-1550 (2006).

Kinetics of the initial steps of G protein-coupled receptor-mediated cellular signaling revealed by single-molecule imaging
,  Y. Lill, K.L. Martinez, M.A. Lill, B.H. Meyer, H. Vogel, B. Hecht,  
Chem. Phys. Chem. 6, 1633-1640 (2005).

Single quantum dot coupled to a scanning optical antenna: A tunable super emitter
J.N. Farahani, D.W. Pohl, H.-J. Eisler, B. Hecht
Phys. Rev. Lett. 95, 017402 (2005).

Resonant Optical Antennas
,  P. Mühlschlegel, H.-J. Eisler, O.J.F. Martin, B. Hecht* & D.W. Pohl
,   Science 308, 1607-1609 (2005).

Partner institution: University of Bielefeld, Germany

Prof. Markus Sauer and his group at the University of Bielefeld, Germany, are internationally leading in the field of single molecule spectroscopy. Their main expertise is in fluorescence correlation spectroscopy of single biomolecules, using photon statistics for quantifying multichromophoric systems, and electron-transfer reactions between fluorescent dyes and amino acids or DNA bases. 

See their webpage for more information:
        University Campus        Old City Hall (with American Muscle Car!)

The city of Bielefeld is in situated in the middle of Europe, in the Northern Part of Germany, near Hannover, Duesseldorf, Hamburg, Bremen, and Cologne. It is also relatively close to the Dutch border.

Recent review articles from the Sauer group:

P. Tinnefeld, M. Sauer, Angew. Chem., Int. Ed. 2005, 44, 2642-2671.
H. Neuweiler, M. Sauer, Curr. Pharm. Biotechnol. 2004, 5, 285-298.
P. Tinnefeld, V. Buschmann, K. D. Weston, A. Biebricher, D. P. Herten, O. Piestert, T. Heinlein, M. Heilemann, M. Sauer, Rec. Res. Devel. Phys. Chem. 2004, 7, 95-125.
D. P. Herten, M. Sauer; Bunsenberichte 2003, 1, 5-16.

Partner institution:  NYMU - Prof. Chou’s lab, Taiwan

Professor Chien Chou and his group can achieve very high sensitivity using their “paired wave SP wave optical heterodyning method” for measuring molecular adsorbent on gold surfaces. From currently attainable sensitivity data and the projected measurable sensitivity, they project that an index of refraction change of 2x10-10 RIU is measurable. 

Prof. Chou also showed data on IgG adsorption to its antibody as well as Ab1-42 to its deposited antibody/antigen has the same level of sensitivity. In particular, for the prion system, the increase in Dn is accompanied by periodic variations in the signal, sometimes extending to 50 sec periods. Some of the periods look like steps upward. A change in the system to Ab1-40 led to change in the Dn increase at same concentrations, but period remains. 

Several new studies have been proposed to be carried out under this international student exchange program. These include:

1.    The oscillations may actually be steps like epitaxial crystal growth. The step may indicate saturation of a particular layer of material. The process of growth may be diffusion controlled in this environment. Changes of protein concentration or antigens for these proteins may change the level of saturation. 

2.    Variation in the temperature of the chamber should change diffusion-controlled rates of step formation. 

3.    The inclusion of membrane to adjust the efficacy of this protein-in-membrane kinetics problem. Such a study will include introduction of supported bilayers. 

4.    The lateral aggregation driven by membrane forces may not be obvious in the solution case. This could also alter the oscillation period that has been observed.

5.    We will attempt to measure this change in the presence of membrane rafts. However, the complication is that rafts are also density-wise and materially different from the fluid domains of the lipid. Hence, the measurement of rafts independent of any proteins needs to be examined and characterized first. 

The primary construct for these studies could revolve around a flow cell and supported membrane bilayer. The proteins, once introduced can then assume activity including initial membrane binding (maybe in raft domains), followed by aggregation kinetics. By looking at the membrane-mediated activity, this may prevent much of the potential protein crystallization processes.

(Left): National Yang Ming University is one of the major research universities in Taiwan. It stands as one of the best for research in biomedicine and biophotonics. It is located on the scenic Yang Ming Shan north of Taipei. 
(Center): Taipei is the capitol and most cosmopolitan city in Taiwan. Its modern outlook is best exemplified by this Taipei 101, currently the tallest structure in the world. During the 2005 “Year of Physics”, the tower boasted the window lights showing E=mc2 .
(Right): Not far from the major metropolis you will find breathtaking scenic beauty of the Eastern Taiwan coast in contact with Pacific Ocean.

References to Prof. Chou’s recent work:

Chan, YH, Chou, C., Wu, JS, Chang, HF & Yau, HF, Properties of a diffused photon-pair density wave in a multiple-scattered medium. Applied Optics 44: 1416, 2005.

Kuo, WC, Chou, C., & Wu, HT, Optical heterodyne surface-plasmon resonance biosensor. Optics Letters, 28: 1329, 2003.

Chou, C., Lyu, CW, & Peng, LC, Polarized differential-phase laser scanning microscope. Applied Optics, 40: 95, 2001.

Partner institution:  University of Toronto - Brian Wilson’s lab

Prof. Wilson’s lab is well known for the work on photodynamic therapy. In the research efforts on the physical nature of PDT, it is now known that three key factors defining the efficiency of a specific PDT treatment are light, sensitizer and molecular O2. 

Light source: How to deliver the light directly to the location of interest. An area of current investigation is the use of molecular beacon as a switch. Can the molecular device be triggered to produce specific wavelength of light only when it has been localized at the prescribed location, such as the surface of cancerous cells? The molecular beacon is a FRET signal that is produced upon signals that change the spacing between donor and acceptor pairs. Initial excitation may be better localized by the use of multi-photon excitation. This process may be expedited by the use of bioluminescence methods. By allowing a chemical signal to trigger luminescence emission, the process can then drive the FRET signal and initiate post-excitation dynamics. 

Sensitizer: Can sensitizers be encapsulated into smaller and localized packages, such as a C60 group? Can these small packages be directed to the locations of interest by smart selection processes: Guided nanostructures?

O2 state: Develop spectroscopic means to identify the efficiency of conversion between 1O2 and 3O2. Bringing in the monitors of hypoxia as molecular indicators of activity in particular state of O2 generation. 

Overall, the new research efforts in Prof. Wilson’s lab is based on the goal of realizing nanobiomedicine at the treatment level using PDT.