Tobacco leaves transiently expressing the green fluorescent protein (GFP)

Research

Background

The plant kingdom provides cures and medicines against numberless diseases and since ages mankind is using herbs and plant extracts for healing. Today, the search for new phytochemicals as lead compounds for the development of novel potent drugs is still ongoing and is one of the focuses of the traditional Pharmaceutical Biology.
A radically new approach in the production of plant-based drugs came up when biotechnology met plant science. Transformation along with efficient regeneration techniques paved the way for the use of plants as production system for pharmaceutical relevant peptides and proteins. The number of enzymes, antibodies, hormones, and other proteins of pharmaceutical interest is increasing steadily and pharmaceuticals made thereof hold a growing share of the pharmaceuticals market. Although the production of recombinant proteins is very expensive and labor intensive, their benefits prevail. To meet the increasing demand for therapeutic proteins and to provide them at a reasonable price alternative tools and production systems are urgently needed. The idea of merging pharmaceutical biotechnology with agriculture -which means using crop plants as a production system for diagnostic or therapeutic proteins- has several striking advantages. Virtually every protein could be expressed in plants by the use of DNA recombination and gene transfer via Agrobacterium-mediated transformation or biolistics. Once transformed the plant could be considered a bioreactor. Using standard agricultural techniques the production process only consumes sunlight, soil, water, and cheap fertilizers instead of expensive nutrients and additional energy. Up-scaling would be only limited by acreage and the ability of further processing instead of fermentation capacity as required by cell and tissue culture.Plant vaccines

Vaccines, the most efficient treatment for disease prevention, are now more than 200 years in use. The progress in biotechnology of the last 20 years introduced a wide range of new techniques and new approaches for vaccine production. Until recently vaccines were usually based on adapted or killed pathogen. Now chimeric, subunit or peptide vaccines broaden the spectrum of immunization.

Moreover, research shows alternative ways of administration, using intranasal or oral application to avoid needle and syringe. This is not only a matter of compliance but also a matter of lowering costs and preventing side effects and risk of infections. Transgenic plants are an exciting approach of combining an innovative production method with an oral delivery system.

Modulation of plant secondary metabolism

Plants produce and accumulate a plethora of so called secondary metabolites, and many of them have a pronounced physiological effect on animals and humans. Therefore, plant metabolites are extensively used as medicines.

One aspect of the research in our lab deals with the elucidation of biosynthetic pathways and with their targeted modification. The tools we are using for metabolic engineering are cytochrome P450 monooxygenases. Especially P450s from the human liver are catalysts with a extraordinary broad substrate acceptance and make them ideal for generating novel metabolites in a given plant.

Research Projects

Lipoprotein vaccines from higher plant chloroplasts

One of our current research focuses is the evaluation of plants capability to produce bacterial lipoproteins in their chloroplasts. Here we use the outer surface protein A (OspA) from Borrelia burgdorferi as a model system. The spirochaete B. burgdorferi – transmitted by ticks – is the causing agent of Lyme disease and OspA was the active ingredient of the first generation vaccine against Lyme disease for humans (Lymerix®).
We generated transplastomic tobacco plants which accumulate OspA to high levels (1% of total soluble protein) and we were able to show that the recombinant protein is lipidated. Moreover, OspA preparations from plants showed similar immunogencity in mice as the bacterial protein.
We are now working on the optimization of lipoprotein production in chloroplasts with additional antigens and focus also on this interesting modification pathway in plants.
Cooperations:
Markus Simon, MPI für Immunbiologie, Freiburg
Juliana Cassataro, Laboratorio de Inmunogenética, Universidad de Buenos Aires, Argentinien

Measures against Malaria

- detailed description coming soon -
Cooperations:
Kai Matuschewski, Institut für Hygiene, Universitätsklinik Heidelberg
Harald Kolmar, TU Darmstadt

Metabolic engineering of plant secondary metabolism with human CYP450 enzymes

- detailed description coming soon-
Cooperations:
Matthias Unger, Lehrstuhl für Pharmazeutische Chemie, Universität Würzburg
F. Peter Guengerich, Vanderbilt Universität, Nashville, TN, USA
Elizabeth Gillam, The University of Queensland, Australia
Oliver Kayser, Institute of Pharmaceutical Biology, University of Groningen, Niederlande