Plant viruses can be engineered in many ways for use by and in humans. Amongst other things, they can be used as scaffold structures for bioactive molecules, which might help improve implants. Prof. Dr. Christina Wege from the University of Stuttgart is studying these and many more options for the use of harmless viruses for human application.
“We eat them every day; they are present in cucumbers, tomatoes, potatoes and fruit. And they are also smoked in the form of tobacco mosaic viruses,” said Professor Dr. Christina Wege from the Institute of Biology at the University of Stuttgart, referring to plant viruses. Wege is now specifically focused on plant viruses, but it took a long time before she eventually decided on a scientific career. She studied biology and journalism, the latter being part of a special programme offered by the University of Hamburg. Despite exciting practical experiences in the offices of PR agencies and NDR North German Broadcasting, Wege eventually decided to go into biological research. “I was interested in plant diseases as a child, especially since a family friend told me about his work for the Schleswig-Holstein Plant Protection Office,” says the researcher.
Wege did her doctoral thesis in the late 1990s on geminiviruses, or more precisely, on the function of different viral proteins. By this time, she had already transferred to the University of Stuttgart along with Prof. Dr. Holger Jeske and other colleagues. Geminiviruses are not only interesting from a scientific point of view; this virus group also includes plant pathogens of huge agricultural relevance. “Geminiviruses are a serious threat to crops and cause extensive harvest losses around the world. For example, such viruses can lead to the complete loss of manioc harvests in large areas of India and Africa. The infected plants do not grow tubers and wither away,” says Wege.
Wege’s research is mainly focused on clarifying fundamental aspects of viral infection and control mechanisms on the molecular level. The research carried out by Wege and her team has contributed to deciphering viral infection mechanisms as well as to the development of virus control strategies.
Wege and her team have found out that viruses are able to penetrate plant tissue more effectively when they occur in company with one or two other different virus species than when they occur on their own. “This might happen when insects transfer several viruses. One of the viruses can then take advantage of the tricks the other species uses to switch off the plant’s defence mechanisms and enter the plant tissue basically unnoticed. I believe that stabilizing the plant’s protective mechanisms on the molecular level is an effective control strategy that enables the plant to withstand virus attacks,” explains Wege.
Although such research is of crucial importance for agricultural production, Wege knows of only a handful research groups worldwide that are working on the molecular biology of these pathogens. She believes that the limited interest is due to the fact that the damage mainly affects southern, economically weaker countries rather than industrialized regions. “Unfortunately, these topics are not in the spotlight of large international research funding programmes,” said Wege. However, this might soon change. Nano- and biotechnologists have become extremely interested in the benefits of plant viruses. Wege has also added a new aspect to her research and is now developing virus-based structures for medical and technological applications. Her research is mainly focused on the tobacco mosaic virus (TMV).
TMV has a rod-like shape; it is a hollow tube compound around 300 nanometres long where coat proteins are arranged around an RNA molecule. “Viruses 100 nm long have some 700 TMV coat proteins arranged cylindrically around the helical RNA,” says Wege. Wege and her team succeeded in modifying TMV coat proteins in such a way that metals could be secreted from the viral tube. This was done in cooperation with partners from the Department of Chemistry. Nanowires three nanometers in diameter could be synthesized from the inner channel. The researchers synthesized copper, nickel, cobalt or alloy nanowires, which can for example be used in sensor and nanoprocess technology.
Genetically modified, synthetic viral RNA and TMV proteins can be used to produce a broad range of different shapes. The researchers from Stuttgart have already produced “nano-boomerangs” with defined arm lengths as well as star-like structures that look like medieval morning stars. “We have developed a modular set that enables us to produce a broad range of different structures. These structures can be straight and of a defined length, they can also be bent or branched,” said Wege. In addition, the structures can be equipped with different docking sites, and this is what makes the viruses medically interesting. The structures can be equipped with docking sites for peptides that can be coupled with enzymes, antibodies or medical substances. The goal is to use these constructs in test systems and drug delivery systems, such as bioimplants or for the treatment of tumours. The virus-based constructs have the major advantage that desired molecules can be attached to the tubes, which consist of hundreds of protein units, in a specific, defined order and even with a density superior to that of other surfaces. Wege explains that it is impossible to apply such a high number of proteins in a defined order on flexible carriers like flat surfaces or fibres.
Wege and Prof. Dr. Günther Tovar from the Institute of Interfacial Process Engineering and Plasma Technology (IGVP) coordinate the University of Stuttgart’s project house NanoBioMater, which is being funded by the Carl Zeiss Foundation. The focus of the researchers is to develop innovative hydrogels, i.e. intelligent biocompatible functional materials for medical application. Wege, who brings virus constructs into the project, explains: “As has been shown by other research groups, it is possible to attach peptides that promote the differentiation of bone marrow cells to the virus constructs. Moreover, peptides that induce biomineralisation and contribute to bone healing can be attached to implantable hydrogels.” The project is also aimed at developing innovative active materials for use in highly sensitive biosensors and controlled catalysis systems that enable the production of complex substances.
International research groups have shown that plant viruses have the potential to be used in the field of tumour medicine. “Potato virus X (PVX) and TMV constructs that are injected into the blood seem to specifically target tumour tissue. We now want to examine this in greater detail with an American cooperation partner,” says Wege. It seems reasonable to not only use PVX, but also TMV for the visualization of tumours. Constructs with fluorescent labels have already been tested in mice.
It is still a pipe dream, but Wege also hopes to develop TMV constructs equipped with specific pharmaceutical compounds that specifically target and destroy tumours. Plant viruses do not normally lead to health problems in humans. High concentrations might however cause allergic reactions. Wege explains the most promising preventive method that currently exists: “The area of the nanotubes that lies between the functional coupling sites can be coated with polyethylene glycol. This reduces the contact the cell has with the coat proteins.”
Wege also mentioned the fascinating possibilities of using plant viruses in the courses she teaches, for example in the three-week laboratory course that is part of the plant virology master’s degree course. Starting in the 2014/2015 winter semester, Wege will also offer a lecture on “nanobiotechnology with plant viruses” that covers cutting-edge developments in plant virus research. Wege is also student advisor and coordinator of the technical biology course. Her advice to the next generation of researchers is: “Do what you like doing, and you will do it well.”
Further information:Prof. Dr. Christina WegeUniversity of StuttgartInstitute of Biology, Department of Molecular BiologyPfaffenwaldring 5770569 StuttgartTel.: +49 (0)711 685-65073E-mail: christina.wege(at)bio.uni-stuttgart.de