Strategy for FOBI

The FOBI board and Scientific Committee have chosen the following four themes as focus areas in the coming years:

1. Sustainable plant production in a changing climate – efficacy, health
2. Biofactories – heterologous expression systems, metabolic engineering, biofuels
3. Host and Microbial interactions – metagenomics, biofilms
4. Human variation in health and nutrition – animal models, documentation, segmentation

The themes unite individual projects into common biological activities as well as the exploitation of generic technologies. The themes represent many key areas of biotechnology and are both cross disciplinary and interinstitutional. We have chosen these themes both to offer focus on important areas for biotechnological research and development and since they offer areas of synergies which are not naturally available within the different participating research environments. By this means, FOBI will support our PhD students in ways which are not normally available to them within their departments.

 

Theme 1: Plant Productivity – efficacy, health Biotechnology and sustainability in a change climate

Keywords: Bioinformatics, Comparative genomics, Ecology, Evolution, Molecular biology, Molecular markers, Molecular plant breeding, Natural genetic variation, Natural products, Plant pathology, Plant pests

 

The 21^st century is bringing major challenges to the planet and the conditions for human life. The most serious challenge remains ever increasing human populations, especially in developing countries. Secondly, globally, both in the industrialised world, but especially within emerging economies, such as Brazil, China and India, expectations for lifestyle and welfare are increasing. It is imperative that these demands are met with sustainable food, fodder and fuel production and use. Both natural fluctuations and the greenhouse effect are resulting in global climate changes which place major challenges on crops, including the need to withstand more variable (and often harsher) weather conditions and altered threat profiles from pests and pathogens. The latter are also increased with increased free trade. Improved technology, and especially biotechnology, will provide solutions to some of these problems. The projects under this section aim to understand the underlying biology which primarily can reduce the impact and secondarily devise ways to take advantage of climate change and other factors on our agricultural systems as well as to exploit the same biology for industrial purposes.

 

Land plants are the ultimate source of most of our food, and are either consumed directly or indirectly via our production animals. On a smaller, but increasing scale, plants are used as sources of pharmaceuticals and other chemicals. In addition to traditional uses as fuel for burning, biofuels, such as diesel substitutes and ethanol are being developed worldwide. In all cases, plants are subject to production constraints from biotic factors such as weeds, pathogens and pests as well as abiotic factors such as cold, drought, flooding and chemicals such as salt and pollution by heavy metals or ozone. The stresses caused by these factors affect not only the yield but also the quality of the products. e.g., by the accumulation of mycotoxins and toxic stress metabolites.

 

The projects under this theme represent applications of biotechnology in order to understand the biological processes underlying plant adaptation to changing conditions including both abiotic and biotic factors, as well as to plant improvement which primarily provide biotechnological applications, for example, by new methods for plant breeding and studies of existing natural and induced genetic variation.

 

A feature of this theme is a link to ecological approaches in order to understand the overall impact of the technologies on the parameters affecting production. Thus recent advances made in comparative genomics for important plant species has led to the development of several new methods and approaches which can be applied for plant breeding. These combine comparative genomics for target chromosome regions with the development of appropriate specific molecular markers. In other words, the use of these genomic approaches provides excellent non-transgenic biotechnology tools for immediate implementation in industry.

 

Links to other areas: the biological processes involved in this theme relate to theme 3.

 

Theme 2: Biofactories – heterologous expression systems, metabolic engineering and biofuels

Keywords: Biochemistry, Bioimaging, Computer modelling, Heterologous gene expression, Protein biochemistry, Metabolic engineering, Molecular biology, Molecular genetics, Nanotechnology, Photobiology, Photosynthesis, Proteomics, Secondary metabolite chemistry, Signal transduction, Synthetic biology, Systems biology

 

The ability to construct cell factories producing valuable products is a rapidly developing field. The products produced range from bulk products such as ethanol to fine chemicals such as pharmaceuticals. Typically, projects within this theme will focus on optimizing production of naturally existing products or on producing novel compounds, which result from the combined action of enzymatic activities which are normally restricted to different cellular compartments or exist in different organisms. Since most novel interesting compounds are discovered in poorly characterized organisms, which are not suitable for production, it is necessary to transfer the metabolic pathway of the compound to an efficient cell factory, which exhibit a superior performance during fermentation.

 

This requires an understanding of the biochemistry that leads to the product and identification of the genes required for making the product. Secondly, most popular cell factory organisms are fully sequenced, which allows for gene targeting. Furthermore, these organisms are generally well characterized, so production of the compound production can be optimized using metabolic engineering strategies suggested by e.g. systems biology based models. In some projects, the establishment of the cell factory will entail the simultaneous successful coordinated expression of a number of genes and the linkage of energy-producing systems with biosynthetic systems. Other projects will aim at increasing the understanding of the biology of the producer strains to facilitate metabolic engineering. This understanding is essential for the construction of the predictive models that is the basis of the metabolic engineering step described above.

 

Typically, individual projects within this theme will focus on specific elements of this complicated process. FOBI will bring students together who work on different aspects of the process allowing them to obtain the full overview of all the different techniques and steps that are required from the discovery of a new product to efficient production in a cell factory. Other projects will aim at increasing the understanding of the biology of the producer strains. This understanding is essential for the construction of the predictive models that is the basis of the metabolic engineering step described above.

 

A second important aspect of this theme is the identification and removal of biochemical pathways leading to undesired, e.g., toxic, compounds that may contaminate the product produced by the cell factory. For example, it was discovered recently by scientists involved in this programme that the fungus Aspergillus niger , a widely used cell factory for the production of food additives (citric acid (E330) and gluconic acid (E574)), as well as for several industrial enzymes used in the food industry, produces important mycotoxins (fumonisins). This unnerving discovery arose following a comparative genomics study of the A.niger genome with that of the important plant pathogenic fungus, Fusarium verticillioides, in which these mycotoxins were originally discovered some 20 years ago.

 

Typically, individual projects within this theme will focus on specific elements of the complicated engineering process that aims at constructing a tailor-made cell factory. An important role for FOBI is to bring students together who work on different aspects of this process allowing them to obtain the full overview of all the different techniques and steps that are required from the discovery of a new product or enzymatic activity to efficient production in a cell factory.

 

Moreover, individual PhD research projects that fall within this theme are typically very cross-disciplinary as they often require many of the elements listed among the keywords, thus ensuring that the PhD students obtain wide-spanning experimental know-how. It is therefore expected that the eight graduates trained within this theme will be a very attractive resource for the growing biotech industry in Denmark, since both the techniques they acquire and the philosophy of the projects are very much in line with the requirements of these industries.

 

Theme 3: Microbial interactions – metagenomics, biofilms, microbes/microbes, microbes/host

Keywords: Antifungal Defences, Bacterial Pathogenicity, Bioimaging, Cellular Transport, Clinical Bacteriology, Comparative Genomics, Fungal Molecular Biology, Gene Mining, Gene Silencing, Heterologous Gene Expression, Marine Microbial Ecology, Metagenomics, Molecular Genetics, Molecular Markers, Signal Transduction

 

Antibiotics can undoubtedly be considered among the most highly significant technological advances made in the last century which improved the survival and health of mankind in many ways. Likewise, fungicides were developed for controlling the most significant eukaryotic disease of plants for agriculture. However, microorganism populations have adapted to these chemoecological changes in their environments and have developed resistance to these substances in many cases. Projects under this theme address these problems in several ways using several biological systems, though screening for new antimicrobial substances, by aiming to understand their modes of action and though understanding natural mechanisms of pathogenicity and disease resistance. Equally, it is important to understand the nature of the differences between commensalism (endophyticism) and pathogenic relationships.

 

The understanding of interactions between microorganisms with animals, plants and other microorganisms is the key to our effort to develop new ways to control infectious diseases of plants and animals and to improve biotechnological production based on microorganisms. Traditionally, there have been few interactions between researchers dedicated to plant diseases and those studying diseases of animals, and similarly very little interaction between industrial biotechnology research and the disease oriented microbiology research.

 

There is, however, increasing evidence for processes common to these areas, for example, the pathogenicity and innate defence mechanisms used by bacteria and hosts in plant and animal disease are similar, and the stress response of bacteria is equally important to diseases and biotechnological production. Hence, there are many possibilities for synergies with the establishment of a common platform. Theme 3 of FOBI constitutes such a platform. In the coming period, Theme 3 of FOBI will focus on host – pathogen interactions, and the possibilities to gaining new understand through the use of modern molecular and post-genomic methods.

 

Projects within this theme all deal with the nature of factors that, seen from the point of the microorganism and the host, are at the front of the interaction between the two parts. Transcriptomics methods, such as microarrays, subtractive screening techniques, EST libraries and genome sequencing will be used to identify pathogenicity and host factors that contribute to the initial interaction. The projects all seek to identify key factors using functional genomics techniques and mathematical modelling. They will contribute to society by proposing novel technologies and strategies for preventing disease or treating infections. Projects will concern the identification of new antimicrobials, the understanding of the mechanisms of the establishment of infection, the interactions between organisms and the characterisation of important microbial communities.

 

PhD students educated in this theme will contribute to basic and applied research in both the public and private sectors and will be educated for jobs in both sectors.

 

Links to other areas: the plant projects link to themes 1, and the animal projects to theme 4.

 

Theme 4: Human variation in health and nutrition – animal models, documentation, prevention, segmentation

Keywords:Biochemistry, Clinical Sciences, Comparative Genomics, Comparative Physiology, Disease Gene Finding, Disease Systems Biology, Functional Genomics, Health Bioactives, Molecular biology, Protein Interactions, Proteomics, Signal Transduction, Health-Disease Balance

 

The tools of genetics and especially comparative genomics provide the opportunity to apply knowledge gained from experimental animal systems, such as rodents (mice and rats), and highly selected mammalian species, such as dogs, to human medicine where informative case control cohorts are much more accessible and not limited to semi-in vitro systems. The projects in this theme use the tools available for these comparative systems to inform human medical research. The projects under this theme will in particular exploit comparative genomics and proteomics in order to identify factors critical for the diseases concerned. Also aspects of comparative physiology as well as nutrigenomics will be included.

 

In the context of nutrigenomics, relatively little is known about genetic variation among people in terms of how they respond physiologically to food components. It is expected, however, that different genotypes will vary in their basic physiology and metabolic pathways – and will differ in susceptibility to and severity in the development of more systemic unhealthy conditions – and, thereby, in their ability to maintain an overall healthy balance. As an extension of these investigations, studies will be made on natural dietary antioxidants and their significance in the context of having protective effects on the gut epithelium.

 

Projects under this theme exploit comparative genomics between and within species, nutriogenomics, and the development of novel therapeutic tools based on biotechnology.

 

Links to other areas: several of the topics under theme 3 link to theme 4.

 

Concluding remarks

The four themes have several roles. Firstly, they are designed to draw focus to areas where there are important applications for society and uses for industry where the basic research associated with a PhD is predicted to make a useful contribution. Secondly, in a large research school like FOBI, with approximately 100 enrolled PhD students, the community risks being too large for the individual student if there is no focus.

 

These themes bridge different kinds of project and research environments to provide a focus which presents all the processes in biotechnology within the specific areas. We will use members of the FOBI board and scientific committee to coordinate, manage and inspire activities associated with each theme. The role of the research school is to work to support and strengthen the role of the graduate schools with which it is associated. This can be achieved by focusing on developing synergies which cross conventional disciplines to provide scientific support in the research community.