General information about the project

Living organisms are equipped with a complex network of proteins between and within their cells. These proteins are continuously active in carrying out essential tasks within the organism, e.g. catalysis of chemical reactions, transfer of information, energy supply or digestion of nutrients. In recent years, a wealth of information has been gathered about the structure and function of many proteins, about the genes encoding them and also about when which protein is produced or degraded. However, these data do not tell us how so many different proteins integrate to constitute a functional cell, how cells form an organism, and how malfunction of proteins can lead to disease. Here, a deeper understanding of location, movement and interactions of proteins is of central importance.

The method of choice to gain information about protein dynamics and interaction within living cells is to attach fluorescent labels and to observe these dyes with highly advanced microscopes. The observed fluorescent light depends on e.g. the orientation and position of the protein within a cell and also changes when the protein in question binds to/interacts with other proteins. Several of such fluorescence techniques are presently available; one of the most powerful ones is referred to as FLIM (Fluorescence Lifetime Imaging Microscopy). Although FLIM has proven to be extremely useful for biological imaging, it has not yet achieved its full potential. Development and application of this highly advanced technique require interdisciplinary expertise in research fields ranging from biology, (bio)-chemistry, and medicine to physics, engineering and software development.

In the research training network proposed here groups from these fields will team up and work together on collaborative research projects, aiming at application and further development of FLIM and training young scientists in an interdisciplinary environment. A second objective of the RTN is to even further improve FLIM and establish a technique called FLIN (Fluorescence Lifetime Imaging Nanoscopy), by combining cutting-edge microscopy technology developed or under development in the network. This step is exceptionally important as FLIM and other present-day microscopy techniques have a resolution limit of about 200 nm (2/100000 cm), insufficient for detailed examination of proteins and their interactions. Compared to FLIM, FLIN will allow for observation at much smaller scale and for a much longer time, opening completely new avenues for biological imaging. For this reason, our proposed network has been named "From FLIM to FLIN".

In the "From FLIM to FLIN" network, young scientists will develop microscope technology in close collaboration with network colleagues who use these new technologies. Applications will focus on investigation of interactions between proteins that may be future targets of drugs and on proteins that act as tiny cellular machines. Knowledge gained in the network may thus be patented, or may form the basis for future patents, either in optical technology, bio-medicine, or nano-technology (the discipline that attempts to utilize the properties of machines or materials at nanometer scale for technical purposes).

The composition of the network, with participants from universities, national research institutes and industry, located in eight countries will on the one hand provide a highly interdisciplinary, international and intersectorial environment for training of young scientists and on the other hand greatly facilitate the transfer of gained knowledge into patentable, commercial products.

The "From FLIM to FLIN" network will thus significantly improve the competitiveness of the ERA and expand European human resources with young researchers skilled in the art and science of advanced nano-scale microscopy.

Overall Objectives

There are two overall objectives for this network. First, in the research training network proposed here groups from multidisciplinary research fields will team up and work together on collaborative research projects, aiming at application and further development of FLIM (Fluorescence Lifetime Imaging Microscopy) and at training of young scientists in an interdisciplinary environment created by partner laboratories in eight countries of Europe. A second objective of the RTN is to further improve FLIM and establish a technique called FLIN (Fluorescence Lifetime Imaging Nanoscopy), by combining cutting-edge microscopy technology developed or under development in the network.

Overall Approach and Methodology

The network is composed of participants from universities, national research institutes and industry providing multidisciplinary expertise in physics, biology, chemistry, engineering and informatics. The partners will join forces to carry out the following research approaches.

• Push ‘imaging of biochemical processes in living cells’ to novel limits by providing for all participating researchers access to the FLIN NanoScope system in Berlin that will be available in the frame of a new EC project (NMP4-CT-2004-01380), called Long-Period Observation of Single (Bio)-Molecular Motors by Novel Minimal-Invasive Fluorescence Lifetime Imaging Nanoscopy (FLIN).
• Extend the observation period and improve time resolution of biological imaging by application of novel detectors.
• Utilize cutting-edge fluorescence microscopy techniques to improve insight into the mechanism of biological and synthetic molecular machines and provide a theoretical background of molecular motor action via computer simulations for comparison with the experimental results.
• Utilize cutting-edge fluorescence microscopy techniques to improve insight into the mechanism of cellular processes exploiting the long-term observation capabilities of the novel detectors.
• Accelerate the development and use of novel fluorescence microscopy techniques through close collaboration between the network partners, exchange of knowledge and transfer of expertise.
• Facilitate the transition from newly developed fluorescence microscopy technology to patentable commercial products through mutual interaction between university laboratories, national institutes and SMEs.
• Train young scientists in techniques complimentary to fluorescence microscopy, such as organic synthesis, molecular cloning, or cell culture.

Train young scientists in skills complimentary to scientific methods such as product development, scientific communication or languages.