Tracking the HI Virus with High-resolution Microscopy

Experts from science and industry are working on new methods of microscopy and advancing microscopy technology to improve our ability to study and understand the molecular processes of HIV infection. Last year, the Federal Ministry of Education and Research (BMBF) approved approx. 4.6 million euros for this joint project called “Chemical Switches and Click Chemistry for High-resolution Microscopy”. Meanwhile preparations for the start of the project are complete. 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. The project coordinator is Prof. Dr. Dirk-Peter Herten, a member of the CellNetworks Cluster of Excellence who also works at the Institute for Physical Chemistry at Heidelberg University.

As Prof. Herten explains, there are more than 35 million people worldwide living with the human immunodeficiency virus HIV. “AIDS, the acquired immunodeficiency syndrome this virus causes, is now quite treatable in the industrialised world. But the lifelong treatment with medication has to be continually adjusted. Because the virus is constantly changing, new treatment strategies are needed,” continues the Heidelberg scientist. “By shedding light on how the virus functions and propagates, we can target our research to develop specific methods for diagnosis and treatment.” Researchers in the joint project are particularly focussed on changes in the T-cells of the immune system effected by the HIV Nef protein. In order to better investigate these processes, the team intends to greatly expand on previous methods of light microscopy.

“The key is the development of new fluorescent probes,” explains Prof. Herten. A new type of direct protein labelling should substantially improve the microscopic image and allow biological structures to be reconstructed in 3D super-resolution. To this end, the scientists intend to synthesise fluorescent probes whose properties can be controlled through chemical reactions. “The goal is to selectively control the fluorescence by adding certain reagents,” stresses the project coordinator. “The new approach to super-resolution fluorescent microscopy can then function independently of light-driven processes.” Furthermore, the methods for protein labelling are to be improved to prevent artefacts and unspecific signals in the imaging.

The researchers are also targeting new developments in the field of 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. Another field of endeavour are optical technologies that permit three-dimensional super-resolution imaging. According to Prof. Herten, these technical enhancements are to be based on standard microscopy systems to ensure wide-ranging and cost-efficient use. “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.“

The industrial partners in the project include ATTO-TEC GmbH in Siegen, Sirius Fine Chemicals SiChem GmbH in Bremen als well as FEI Munich GmbH and TOPTICA Photonics AG in Munich. The research work at Heidelberg University will be supported through BMBF funds in the amount of approx. 670,000 euros.