Chemical probes to out-sleuth HIV
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- The researchers want to depict molecular processes in cells more accurately using superimpositions of fluorescence microscopy recordings of the cytoskeleton (grey) with high-resolution reconstructions produced by chemically controlled probes (yellow-red). Source: D.-P. Herten, Heidelberg
16.04.2014 -
Around 35 million people around the world are infected with HIV. While dependable medicines for the treatment of AIDS have now been developed, there is still no cure for the immune deficiency disease. The molecular mechanisms of HIV infection are yet to be elucidated despite the accumulation of detailed knowledge on the molecular processes. This knowledge is nevertheless crucial for the eventual development and provision of targeted treatment for HIV patients. Now, within the framework of the collaborative project ‘Chemical Switches and Click Chemistry for High-resolution Microscopy’, efforts are underway to develop new methods and technologies for high-resolution microscopy. The initiative includes contributions from experts in academia and industrial research. These are concentrating on the use of molecular probes that can be controlled by chemical means. The joint project is funded with 4.6 million euros by the Federal Ministry of Education and Research.
The three-year Switch Click Microscopy project will involve scientists from Heidelberg University and Heidelberg University Hospital, the University of Würzburg, the European Molecular Biology Laboratory in Heidelberg as well as experts from four companies. Thereby, the research team has made a deliberately choice of the HI virus as a test object for the newly developed technologies. This is because the virus undergoes continual change and thus demands a constant updating of treatment methods. “By shedding light on how the virus functions and propagates, we can target our research to develop specific methods for diagnosis and treatment,” explains project coordinator Dirk-Peter Herten. Researchers in the joint project are particularly focused on changes in the T-cells of the immune system affected by the HIV Nef protein.
Synthetic probes steer fluorescence
One objective of the project is to further develop current light microscopy methods in order to more closely examine the processes of these changes. “The key is in the development of new fluorescent probes,” says Herten. To do this, the researchers want to synthesise fluorescent probes whose properties can be controlled by chemical reactions. Here, the fluorescence can be tightly controlled through the addition of reagents. “The new approach to super-resolution fluorescent microscopy can then function independently of light-driven processes,” says project coordinator Herten. Alongside, the methods for protein labelling are to be improved to prevent artefacts and unspecific signals in the imaging.
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High resolution in 3D
Another field of research is working on optical technologies that will enable simultaneous, high-resolution, three-dimensional depictions of the desired subject. “Improving microscopic imaging makes understanding the biological processes surrounding the HIV immunodeficiency virus easier. This knowledge will allow us to focus the search for new AIDS drugs much more effectively,” says Herten. The joint project will also be working on completely new techniques in microscopy technology, including methods to simplify adding reagents during microscopy as well as new light sources whose output and wavelengths are attuned to the newly developed fluorescent dyes. These technical enhancements will be based on standard microscopy systems to ensure wide-ranging and cost-efficient use.
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