Joint Research Projects (2019-2022)

Funded by

Screening new to nature libraries of diterpenoids generated by synthetic biology for novel anti-tumor activities - COMBIOSCREEN

Prof. Dr. Alain Tissier (Leibniz-Institute of Plant Biochemistry) and PD Dr. Margret Köck (Martin Luther University Halle-Wittenberg)

Next generation sequencing technologies now allow access to the transcriptome and genome and virtually any species. In COMBIOSCREEN, libraries of genes encoding candidate enzymes involved in plant diterpenoid biosynthesis will be generated using a synthetic biology approach based on Golden Gate cloning and combined in high-throughput  for expression in yeast, which has proven to be a highly efficient host for production of plant terpenoids. An automated mass spectrometry screening will detect which gene combinations generate new products, which will then be tested for activity against cancer cell lines. The structure of compounds with activity will be determined and their mode of action on tumor cells extensively characterized.

INDUCEPROT – Induced Accumulation of Recombinant Proteins in Barley Endosperm

Dr. Götz Hensel (Leibniz-Institute of Plant Genetics and Crop Plant Research) and Prof. Dr. Marcel Quint  (Martin Luther University Halle-Wittenberg)

INDUCEPROT will generate a barley ‘driver line’ as production platform for high-value proteins. Conditional depletion of the endogenous seed storage protein HORDEIN will favor production and accumulation of recombinant target proteins directly in the grain. The three-step process comprises a) grain-specific (endosperm) expression of the target protein, b) induced inactivation of HORDEIN accumulation, and c) comparison to existing protein production systems. The combination of innovative in vivo protein modulation and site-directed mutagenesis tools will allow to shift from accumulation of endogenous HORDEIN towards accumulation of target proteins by altering plant growth temperature. This will allow an upscaling of plant-based production of protein pharmaceuticals.

MAGIC-RESIST

Prof. Dr. Klaus Pillenand Dr. Wiebke Sannemann (Martin Luther University Halle-Wittenberg) and Prof. Dr. Frank Ordonand Dr. Albrecht Serfling (Julius Kühn-Institute)

The major goal of MAGIC-RESIST is to significantly enhance pathogen resistance of winter wheat breeding programs through the detection of quantitative resistant genotypes based on newly established multi- and hyperspectral imaging methods in the field. Selected resistant wheat genotypes, identified through spectral imaging, can be included into wheat breeding programs. This will include the identification of quantitative resistant genotypes in population, differentiation of resistant, quantitatively resistant and susceptible genotypes against rust and Fusarium pathogens, mapping of QTLs controlling pathogen resistance, incorporation of valuable pathogen resistant genotypes into breeding programs and evaluation of pathogen resistant winter wheat genotypes for the German and the European seed market.

Development of new phytoeffectors reducing drought stress (Phytoeffectors)

Prof. Dr. Ludger Wessjohann (Leibniz-Institute of Plant Biochemistry) and Prof. Dr. Edgar Peiter (Martin Luther University Halle-Wittenberg)

Drought is the most relevant stress factor for reduced yields in agriculture. Low molecular weight phytoeffectors are able to favorably modify  the plant’s response to drought stress. The aim of the proposed work is to validate the molecular target and to develop the initial hits into applicable development compounds. Structural optimization using tools of medicinal chemistry (computational models and synthetic derivatives), analytical and plant biochemistry will be used to improve the activity, solubility and leaf absorption of compounds, based on a new  in vitrotarget enzyme assay and various drought stress assays using whole plants (Lolium perenne and barley). Measurements of the compounds in roots and shoots will give additional  information on absorption and transport of the compounds, a field largely untapped in plant sciences. Finally, we expect to have a lead compound optimized for plant application that can be developed for field application, registration and production.

Weed control by biological compounds identified in necrotizing plant pathogenic fungi (WOLF)

Prof. Dr. Holger Deising and Prof. Dr. René Csuk (Martin Luther University Halle-Wittenberg) and Dr. Norbert Arnold (Leibniz-Institute of Plant Biochemistry)

Recent controversial discussions on the risk imposed by synthetic herbicides, e.g. glyphosate, explain the growing public demand for bio-compatible weed control. Indeed, within the different categories of herbicides, bio-herbicide are predicted to grow at the fastest rate (23.5% compound annual growth rate during the forecast period 2016 - 2022). In this project we will employ highly destructive plant pathogenic fungi to identify novel lead structures of plant necrotizing molecules. These structures, representing a novel class of bio-compatible herbicides, will be chemically modified to optimize their efficacies.

Joint Research Projects (2016-2019)

Funded by

The Ethics and Economics of Modern Agricultural Myths (AGRIMYTHS)

Prof. Dr. Ingo Pies and Dr. Stefan Hielscher (Martin Luther University Halle-Wittenberg) and PD Dr. Vladislav Valentinov (Leibniz Institute of Agricultural Development in Transition Economies)

A striking feature of the food and fiber system, both worldwide and in Germany, is the controversial nature of public discourse about a range of issues including the role of small-scale farming, GMOs, and financial speculation with foodstuffs. This discourse is framed not only by extraordinarily rigid mental models (i.e., myths) but also by moral semantics. For these reasons, the assessment of risks and benefits of many agricultural and life-science innovations seems to remain particularly impervious to scientific evidence. The project seeks to contribute to rationalizing these debates by combining the tools of ethical and economic analysis. The project will be implemented by two PhD students. One of them will be responsible for the ethical part and be affiliated with the Chair of Economic Ethics at Martin Luther University Halle-Wittenberg. The other student will be responsible for the economic part and be affiliated with IAMO. Both students are supposed to work closely together and be jointly supervised by the principal investigators.

The key activities will include:

  • a discourse analysis of the current debates on the modes and challenges of agricultural production. The discourse analysis will encompass relevant contributions that appeared in major German and international print media outlets
  • a clarification of the popular moral beliefs about agriculture, agricultural production methods and innovations. To this end, the project will perform expert interviews with relevant organizations and actors of the food and fiber system, including farmer associations, both conventional and organic producers, NGOs and experts from politics, academia as well as from the media. Interview guidelines will contain open questions related to the moral dimension of agricultural production, e.g. with respect to the aspects of food security and small-scale farming
  • innovative, qualitative-empirical methods to analyze the discourse and interview data. This will allow generating causal connections to reveal meaningful relationships between basic moral concepts identified within text samples. Interpreting these connections as representations of the mental landscape of interviewed and authors will help to disclose the patterns of moral argumentation and to classify the identified moral arguments using a semantic analysis.
BEP – Barley Epigenome Platform
In the nuclei of plants like barley, DNA is wrapped around histone proteins. The three-dimensional packing of these conglomerates, which are called nucleosomes, is able to regulate stress responsive expression of certain genes via DNA- and histone-modific
In the nuclei of plants like barley, DNA is wrapped around histone proteins. The three-dimensional packing of these conglomerates, which are called nucleosomes, is able to regulate stress responsive expression of certain genes via DNA- and histone-modific

Prof. Dr. Klaus Humbeck (Martin Luther University Halle-Wittenberg) and Dr. Nils Stein and Dr. Martin Mascher (Leibniz Institute of Plant Genetics and Crop Plant Research)

Industry partner: Saaten-Union Biotec GmbH

During development, plants have to cope with an ever changing environment. In this struggle, some plants perform much better than others. For crop plants, the ability to withstand adverse stress conditions, e.g. drought, finally determines yield. Having in mind that global agriculture has to deal with a growing world population and at the same time, due to climate change and other constraints, with increasing adverse environmental conditions, it is of immense economic importance to breed plants with high yield even under environmental stress. Therefore, we have to learn how some plants are able to withstand such stresses and we have to integrate this novel knowledge into targeted breeding approaches. Since plants responses to environmental stress mainly depend on coordinated and highly regulated expression of the right genes at the right time point, understanding of the underlying regulatory mechanisms is a prerequisite for breeding better crops. Recently, exciting new results revealed a major role of so called epigenetic mechanisms in regulation of gene expression, which act via reorganization of the chromatin in the nuclei of the plant cells, where the DNA-based genes together with proteins are structurally organized. These epigenetic factors seem to build a higher order control level of plants performance and therefore are highly interesting targets.

The project aims at the identification of such epigenetic key factors determining plant`s fitness also under stress conditions. We want to establish in Saxony-Anhalt an epigenome platform for crop plants which enables genome-wide analyses of epigenetic mechanisms, namely histone and DNA modifications in the nuclei, combining the molecular plant biology, biochemistry, epigenetic, plant physiology and bioinformatics expertise of the labs. In our first approach we will focus on natural and stress-induced leaf senescence in barley plants, which is one major reason for massive loss in yield. However, our long-term aim is to use this unique and novel epigenome platform for various actual agronomic challenges, and to integrate the power of this platform into breeding approaches for better crops with high yield even under adverse conditions.

Purified Hydrophilized Phytosterin Intermediates - From Paper Pulp Waste to High Value Flavor Modifiers (Dulcesterol)
© Fraunhofer CBP

Prof. Dr. Ludger Wessjohann (Leibniz Institute of Plant Biochemistry) and Gerd Unkelbach (Fraunhofer CBP)

Industry partner: Zellstoff Stendal GmbH, Symrise AG

Phytosterols and -sterines can be found in all plant products. A commercially interesting source is from byproducts of the pulp industry. The most prominent products derived from these substances are margarine substitutes with a cholesterine lowering health promise (Becel® diet etc.), nowadays produced out of soy bean. Extraction and purification from paper pulp waste streams can offer a high valuable source for these substances. Many even higher value applications are in sight, if the more abundant sterines can be converted to rarer, highly priced derivatives, or modified to provide properties, especially by hydropilization, desirable for their use as industrial high value intermediates for pharmaceutical, cosmetics or flavor applications.

To generate Phytosterines and -derivatives the project focuses on: (1.) analyzing and purifying phytosterine mixtures from local factories and (2.) transform suitable candidates by selective catalytic processes, primarily biocatalytic or fermentative processes, to higher value derivatives. A special focus will be on phytosterines oxygenated in defined positions, as such hydrophilized derivatives have potential as intermediates for (plant) hormones and drugs.

Therefore the objectives are:

  • develop a method for the rapid qualitative and quantitative analytical profiling of tall oil and other potential sterine feedstock with respect to di- and triterpenoids.
  • develop a method to identify unsaturation and oxygenation patterns of these triterpenoids, ideally in the crude material. Select prime candidates for further development.
  • develop an isolation method for the prime candidate(s).
  • upscale its production.
  • develop biocatalytic, fermentative or chemical methods to selectively oxidize or other modifications.
  • upscale the most successful modified sterine production
  • obtain bioactivity profiles for the novel sterines

 

Pathogen resistance achieved by plant-induced silencing of fungicide target genes (PARASIT)

Dr. Jochen Kumlehn (Leibniz-Institute of Plant Genetics and Crop Plant Research) and Prof. Dr. Holger Deising Martin Luther University Halle-Wittenberg)

Industry partner: KWS Saat SE

Protection of plants against pathogenic fungi is indispensable for a sustainable and safe production of plant biomass. Since plant protection is based on two major pillars, i.e. chemical plant protection and plant breeding, it has to be kept in mind that resistances are likely to occur in fungi. Breaking of specific resistance (R) genes as well as the occurrence of fungicide-resistant pathogens takes few years only, as demonstrated for various R genes and fungicides.

Host-induced gene silencing (HIGS), introduced by Nowara et al. 2010 (Plant Cell 22, 3130-3141) at IPK Gatersleben, allows the down-regulation of specific fungal target genes via RNA interference (RNAi). Because HIGS acts on the RNA level, an exclusive effort on either individual or a well-defined group of pathogens is possible. If HIGS is targeted against fungal genes affecting viability and/or virulence, it can lead to a declining virulence of the fungus.

However, for various reasons many pre-selected genes proved unsuitable for effective HIGS-derived resistance in previous studies, underlining the importance of a thorough pre-evaluation of the suitability of possible HIGS targets. A comprehensive chemical and genetical screening of target genes is crucial to test their indispensability for fungal virulence and to determine the required degree of transcript abundance down-regulation to erase virulence.

Chemical screens may be difficult, due to the lack of known inhibitors. Thus, we will establish a method to genetically evaluate possible RNAi targets for their suitability for HIGS approaches employing site-directed mutagenesis using customized RNA-guided Cas endonuclease technology.