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.
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.
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
Prof. Dr. Markus Kulmann and Prof. Dr. Thomas Altmann (Leibniz Institute of Plant Genetics and Crop Plant Research) and Prof. Dr. Edgar Peiter (Martin Luther University Halle-Wittenberg)
Industry partner: Saatzucht Josef Breun GmbH & Co. KG
Drought stress in the terminal phase of barley development leads to severe losses in grain yield. It has been shown that during the reproductive phase of development the plant is most sensitive to water deficit. While drought stress before anthesis leads to a reduction in the grain number, drought stress after anthesis results in reduced seed filling. In our previous research we identified genes involved in drought stress response with suppressor function. The promotor regions of these target genes will be transcriptionally inactivated to improve drought resistance in barley. The mechanism of RNA-directed-DNA-methylation will be applied to silence genes with suppressor function for drought resistance and grain size in barley (Hordeum vulgare).
Transcriptional gene silencing is a mechanism inactivating the targeted gene via methylation of its promotor region. Sequence specific methylation will be achieved by stable and transient expression of a hairpin construct directed against promotors of target genes with suppressor function in barley drought resistance. The heritability of this type of inactivation even in the absence of the silencer transgene was previously reported in Arabidopsis. Applying this method to barley may establish to a new method of stable gene activity modification other than genetic engineering of plants.
This project will help investigating a new technology that can be applied to improve crop plant performance during drought stress. The stability of grain yield under drought stress is an important issue, not only for local breeders, but will also help to secure food and feed worldwide under changing climate conditions.
Prof. Dr. Ingo Schellenberg and PD Dr. Helmut Baltruschat (HS-Anhalt) and Prof. Dr. René Csuk (Martin Luther University Halle-Wittenberg)
Industry partners: Medicos Service GmbH, Helm AG
Natural compounds play an important role among various sources in the search for new pharmaceutical, cosmetic and plant protection products. The demand for plant-based chemicals increased continuously in recent years; the average annual growth was about 9-10 %. This is mainly due to reduced costs for drugs, cosmetics, and food when they were obtained from renewable resources by extraction. This approach is more sustainable than their classical chemical synthesis from petrochemical intermediates. While plant extracts played a special role in the past as a source for drug substances, many infectious diseases couldn’t be successfully combated until the discovery of natural antibiotics from active bacterial or fungal substances. Every year approximately 15% of the world’s harvest yields are attacked and destroyed by pathogens like phytopathogenic fungi, whereby it is expected that such attacks will increase in the future as a result of changes in climate conditions.
Since heavy metals are toxic to plants, these habitats are often almost completely free of vegetation. Only a highly specialised flora made up of species that are tolerant to heavy metals are able to survive under such extreme conditions. Fungi, with the exception of arbuscular mycorrhizal fungi, have not yet been investigated in heavy metal communities and have also not yet been isolated and characterised from these locations. However, since fungi might play a major role in the development of adaption and survival strategies in exceptional habitats, it makes sense to evaluate these in heavy metal communities.
As former mining area for copper shale (Mansfelder Land) and ore (Harz Mountains) Saxony-Anhalt has a multitude of waste rock heaps that are extreme habitats contaminated with heavy metals. We have access to nearby heavy metal sites with different histories of origin that can be used to isolate fungi and collect plants for the production of new bioactive metabolites. Fungal species associated with plants from heavy metal sites, which support plants to alleviate both abiotic and biotic stress and accordingly to survive under extreme conditions are expected to have a particularly high potential for containing yet unknown bioactive substances. Here, the chances are quite high for discovering bioactive compounds during screening, which have not yet been identified before. Furthermore, new cultivation methods for fungi from extreme habitats will be developed and established within the framework of this project. Targeted changes in abiotic stress levels under culture conditions are expected to stimulate secondary metabolite formation, thereby providing new insights into the production of biomass and active substances. Chemical-biological quality assessment and first formulation studies within the framework of the formulation platform will lay a cornerstone for subsequent projects that apply practical formulation of newly identified, characterised and isolated bioactive substances, particularly for plant protection products, but also for cosmetics and pharmaceuticals.
Subproject 1: (Prof. Dr. Ingo Schellenberg, PD Dr. Helmut Baltruschat HS-Anhalt)
Natural products are important sources of novel bioactive compounds and continued to be of interest to pharmaceutical companies and agriculture. They have been a prolific and continued source for new lead compounds and pharmacophores in drug discovery. In the last year, a huge number of publications dealing with the topic secondary metabolites isolated from endophytic fungi could be mentioned. Those studies suggest that there is a high potential in using those microorganism to produce bioactive compounds in a usable scale. Half of the pharmaceuticals and three quarter of the antibacterial agents admitted in the last 20 years are based on natural compounds.
The focus of interest is primarily on areas characterized by extreme abiotic conditions like high salt content, drought, heat or coldness. In recent publications, the high biological and chemical diversity of endophytic fungi located in extreme habitat was documented. The Copper mine Dumps fulfil this requirement because of their high toxic content of heavy metals. Furthermore, investigations of endophytic fungi and their secondary metabolites of the selected area are still missing.
The aim of this project is evaluating bioactive secondary metabolites for pharmacological and agricultural applications with the help of a multi-stage-program. This includes the extension of the platform for isolation and characterization of plant-based secondary metabolites that is already established in the Center of Life Science (CLS). Finally the development of an extraction-, screening and formulation-pipeline for bioactive compounds, isolated from endophytic fungi of heavy metal plant communities, will be achieved. Endophytic fungi that are not investigated in a biotechnological manner till now will have a significant importance. After isolation of endophytic fungi from roots of heavy metal tolerant plants, a functional - especially the antifungal activity against selected phytopathogens- and taxonomic characterization will follow. In case of a considerably high bioactivity, suitable cultivation conditions as well as extraction- and cell disruption- methods -regarding to its bioactive potential will be developed. With the help of different analytical Methods like (preparative) HPLC, NMR, GC-MS and LC-MS/MS, secondary metabolites, with the responsibility for biological activity, will be isolated and elucidate structurally. Furthermore the determination of the structure-effect-mechanism will be a part of investigations.
Subproject 2: Isolation, identification of secondary natural products from plants and fungi and establishing a screening platform in search of novel cytotoxic compounds and enzyme inhibitors.
(Prof. Dr. René Csuk, MLU Halle)
Secondary natural compounds from plants and fungi are important sources in the search for new pharmaceutical, cosmetic and plant protection products. The demand for plant-based chemicals increased continuously in recent years. Often, these compounds are complex in their structure and they carry a variety of functional groups. Thus, it is easier and more economic to obtain them from their natural sources by extraction. This approach is also more sustainable than their classical chemical synthesis from petrochemical intermediates. The large and still increasing number of publications looking at bioactive substances obtained from plants, bacteria, fungi and algae is attributed to the importance of this field. The fact that around 50% of the active pharmaceutical ingredients over the past 20 years have consisted of natural substances or have been developed on the basis of natural chemical leads highlights this importance. This proportion is even higher in certain therapeutic areas, for example in cancer drugs (74%) and in antibacterial agents (78%).
In recent years, a robust screening platform for extracts from plants has been developed and established. Within this project, the screening platform will be enlarged to allow a “bioactivity-guided” screening of raw extracts (for example, using 96 well micro-titer plates, combined with HPLC-ESI-MSn but also the development of methods for “rapid assaying” applying colorimetric as well as hyphenated MS techniques) to find new cytotoxic compounds (employing up to 20 different human tumour cell lines) as well as to identify new inhibitors for an array of different enzymes including ureases, cholinesterases, carbanhydrases etc. For the enzyme assays UV-vis, fluorescence as well as bioluminescence-based detection methods will be used, while for the cytotoxicity assays staining and fluorescence microscopy, DNA-laddering and FACS-based methods are applied. Whole-plant fractions (or whole plant-compartment fractions) considered to be bioactive, are separated into single compounds. Starting from these lead compounds, chemical modifications are performed to provide compounds of higher activity, better selectivity and to improve bioavailability.
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.
Dr. Daniela Pufky-Heinrich (Fraunhofer CBP) and Prof. Dr.-Ing. Thomas Hahn (Martin Luther University Halle-Wittenberg)
Industry partners: SunCoal, B+B Engineering
Bio-based phenolic compounds can be made available by the depolymerization of lignin isolated from wood. Cleavage of the phenolic macromolecule lignin enables the production of mixtures of aromatic building blocks for synthesis. These can be used directly as raw material, e.g. for phenol formaldehyde resins, polyurethanes or in epoxides, or can be converted into the classic aromatic compounds, benzene, toluene, xylene or phenol, after further separation and defunctionalization. A variety of methods are suitable for this, such as hydrolysis, oxidative and reductive cleavage or enzymatic conversion.
The process of base-catalyzed depolymerization (BCD) of lignin results in hydrolysis of the ether bonds in the lignin macromolecule and thereby in the production of monomers, dimeric and oligomeric alkyl-functionalized aromatic compounds. The BCD process is carried out in aqueous or alcoholic systems at temperatures of up to 350°C and at 250 bar. Scaling of this process at the pilot scale was carried out successfully at Fraunhofer CBP. We investigated and optimized the continuous process of chemical cleavage of lignin and the subsequent separation and purification of the aromatic fractions using a multi-stage process design. The alkaline solution is processed at a capacity of up to 20 kg / h and subsequently separated using mechanical and thermal techniques.
The project includes further scientific investigation of the catalytic cleavage of lignin in order to gain a deeper understanding of the reaction mechanism, and then to define product specifications of phenol derivatives and to scale the process. Moreover, development and optimization of down-stream and purification methods for the selective separation of the desired products will be carried out. In order to increase the technology readiness level of the BCD process and thus, to develop an industry relevant process an overall approach regarding material and energy efficiency has to be established as well as its technical feasibility and implementation investigated.