Hans-Knöll-Institut für Naturstoff-Forschung e.V.

Mission Statement

The mission of the HKI is to strengthen basic and applied research on natural products with the aim to develop novel concepts and technologies for and the discovery of lead compounds with applications in the life science sector. We try to focus our work on aspects which complement the activities of industrial companies and we provide support functions for the entire scientific community. Our goal is to efficiently transfer acquired knowledge, technologies and products from the basic research laboratory to commercial applications in the bioindustries.

We are convinced that small molecules from nature remain to be an exquisite source of chemical structures for the development of new drugs. Moreover, natural products provide intelligent tools for the analysis of macromolecules and thus will facilitate the exploitation of the emerging structural information derived from the genome level.

Natural products have been designed by nature for nature. They have evolved together with their targets to serve a multitude of biological needs. Studying the interaction of natural products with their macromolecular target will help us to understand the complexity of biological communication. This knowledge will allow us to design novel chemical structures to treat and/or prevent diseases.

Our guideline is "Learning from Nature". We embark on concepts and technologies which can be derived from the "problem solving arsenal" of nature.

Research and Technology Concept

Research and technology development at the HKI is governed by the following leitmotif:
"Natural Products - Mediators of Biological Functions and Cellular Communication Networks"
Interactions of macromolecules (proteins, nucleic acids, carbohydrates, lipids) among each other and the interactions between macromolecules and small molecular weight compounds form the basis of intracellular and intercellular communication. They constitute the cellular principles for molecule fluxes, energy metabolism and signal transduction. Intra- and intercellular communication networks lay down the basis for spatial and temporal control of growth, differentiation and reproduction. Their dysfunctions lead to the development of diseases and/or a reduction of quality of life.

The main focus of research and technology development at the HKI are low molecular weight compounds of microbial origin. The action of these small molecules, their derivatives and biomimetics upon communication pathways is of particular interest in the design of new concepts to address physiological and pathophysiological states, thus preventing and/or curing diseases. A very rapid gain of knowledge in the fields of genomic research catalyzes our search for molecular targets and opens up new strategies to explore the biosynthetic potential of nature for new bioactive compounds.

Research Strategy and Research Fields

Our research rests on five "Research Departments" (see below: "Organizational structure/Research Departments"). The research fields are chosen in such a way to support the discovery process for new chemical entities derived from natural sources with an application potential in the life science sector. The research activities at the HKI are driven by biology. We are convinced that the next decade will open up new possibilities to exploit natural diversity based on comprehensive genomic information, sophisticated analytical systems and physical handling technologies. Combining these driving forces with molecular knowledge on disease development and pathogenic states provides the key for an individualized therapeutic approach of high specificity and sensitivity.

With respect to medical indication areas, we adhere to a double strategy. We are open to all indications which can be addressed by molecular targets, thereby focusing on screening systems which are based on macromolecular interactions and assays which display interesting microbial phenotypes; at the same time we are particularly interested in the antiinfectives field where a significant expertise is present in various follow-up test systems including animal models.

Main lines of research at the institute are:

• Developing means of analyzing gene functions and applying functional genomics information to identify molecular targets and to study target/effector interactions (Functional Genomics / Infection Biology)
  
• Studying and exploiting natural sources of chemical diversity using biological and chemical methods (Chemical and Biological Diversity)
  
• Enlarging the structural and thus functional diversity of small molecules by chemical derivatization of lead compounds and de novo synthesis on the basis of natural building blocks (stochastic synthesis) (Structure/Function Analysis)
  
• Utilizing high-tech instrumentation to determine the chemical structure of novel compounds and to examine their effect on cellular systems (Analytics & Bioinstruments Development)
  
• Developing target-oriented screening assays (focus on cell-based assays) and applying them in combination with high-throughput handling and analytical systems (Analytics & Bioinstruments Development)
  
• Developing technologies to control biotechnological production processes and to fully exploit the biosynthetic capacity of microorganisms utilizing molecular probes in combination with data management tools to analyze the physiological status of cells (Analytics & Bioinstruments Development)

These research fields are supported by a strong technological infrastructure which complements a long standing tradition and experience on process engineering, metabolite screening and biological profiling of novel lead structures (see below: "Organizational Structure/Technology Departments"). A close interaction between Research Departments and Technology Departments is vital for maintaining a competitive research environment in our fast moving field of scientific innovation.

Internal Product Line (IPL)

The organizational units of the HKI (see below: "Organizational Structure") are linked by a matrix-like structure which ties most Departments together to form the HKI "Internal Product Line" (IPL). The IPL serves to generate a "HKI-Project" which has as its unique task the search and development of new bioactive compounds using the HKI-internal resources. Starting with the identification of novel microbial and chemical sources, the isolation and structure elucidation of unknown chemical entities, the detection of biological activities on the basis of a hierarchically organized screening platform, the IPL leads to biologically characterized new lead compounds which are produced at the HKI Pilot Plant for Natural Products. With this tight multidisciplinary network we demonstrate our capability to work process- and product-oriented. And we generate manifold interdisciplinary working fields which stimulate our basic and applied research projects.

The IPL is the main compound outlet of the HKI. A broad repertoire of screening systems is operated by a number of laboratories situated in different HKI Departments. Based heavily on microbial and viral assays combined with target-oriented as well as enzymatic assays they provide a first "finger print" of a new compound. Toxicological analysis and preliminary bioactivity profiles using in vitro and in vivo models lead to a set of data which may form the basis for further collaborations with industrial partners.

The daily work of the IPL is organized buttom-up by the "IPL-Team" consisting of the expert scientists directly involved in the working programs. If necessary, priority setting and allocation of resources is decided by the "IPL-Committee" (consisting of most Department Heads and the Scientific Director). Most importantly, the information generated is deposited in a HKI-internal data handling system which allows to retrieve and evaluate compounds with interesting profiles. This is the basis to promote further external collaborations, i.e. with pharmaceutical industries.

Microbial Depository and Natural Products Pool

The Institute has a collection of about 20.000 microorganisms consisting mainly of Actinomycetes which has its origin in the former "Zentralinstitut für Mikrobiologie und Experimentelle Therapie (ZIMET)". Most entries belong to the varieties of nocardiaformic and coryneformic bacteria. However, in the past five years, we were able to steadily increase the fraction of higher fungi (ascomycetes, basidiomycetes, fungi imperfecti). We maintain a constant collection and isolation program and we acquire collections of microorganisms from various academic sources. This pool of microorganisms and the sample collection derived thereof forms the basis for many screening collaborations.

Since 1996 a "Natural Products Pool" is being built up. At present the pool consists of approximately 3500 pure chemical compounds of microbial and plant origin. Most compounds are direct isolates from nature, however a small number of chemical derivatives is included as well. The pool is fed by a large community of mainly academic institutions. The compounds are deposited in microtiter master plates the replica of which are shipped to the various screening platforms of a small number of dedicated pharmaceutical partners. All rights on the compounds deposited remain with contributors. As a compensation, the HKI is allowed to use the pool for own screening purposes and scientific collaborations.

External Collaborations

As a research institute with its major aim to facilitate technology and product transfer from basic research to application we look for cooperations with academic as well as industrial partners.

Embedded in the local university structure (the HKI has seven joint professorships with the Jena University) we profit from an excellent scientific environment with manifold possibilities for collaborations. In addition to the Jena University and the University of Applied Sciences, a broad spectrum of research institutions (research institutes of the Max-Planck-Gesellschaft, Fraunhofer-Gesellschaft, Wilhelm-Leibniz-Gesellschaft and several research institutes of the Federal State of Thüringen) is present within the city limits of Jena. Among the research contacts with the Jena University joint projects with laboratories of the Life Science and Medical faculties have been particularly productive. With respect to the extra-university research establishments the physics-oriented institutes have had the most significant impact on our work. Furthermore, a large number of scientific collaborations exist with additional research partners in Germany and beyond.

Our collaborations with industry are traditionally very broad. Judging from the financial volumes collaborations with large pharmaceutical companies make up for the major part of our activities. Most projects are strongly product-oriented, i.e. consist of screening activities for new natural lead structures or focus on specific research and development work on specific compounds with interesting biological profiles. Our Natural Products Pool often serves as an attractive starting point for joint ventures. A number of projects are centred around the development of biological and/or biotechnological tools. Collaborations with small companies are often service-oriented or involve the Institute as an application platform for the development and evaluation of modern bioinstruments.

A shift of our cooperations from large companies to small and medium-sized companies is currently influencing our industrial network and will most likely lead to a new balance of external contacts.

Intellectual Property Position

We maintain an active intellectual property policy on the basis of our in-house patenting and licensing know-how and our own partnering strategy. The HKI applies for approximately 20 to 30 patents yearly, most of them claiming substance protection. As our institute has its own legal status separate from the university system all intellectual property rights remain with the HKI.

We believe that product and technology transfer is served best if research and development activities are tied to an active patenting strategy. Furthermore, the Institute must follow an active patenting policy in order to attract commercial companies to take over promising HKI-projects and to interest them to invest in further research and development work.

In general, the HKI takes the responsibility to file the priority applications. In an existing project with an industrial partner the patent is usually transferred with the right and duty to exploit the invention. If an industrial partner does not exist an active acquisition effort is started with the goal to initiate a cooperation project with a strong company willing to perform further development work and ready to finance additional research activities at the Institute.

Organizational Structure

In order to assign clear tasks and evaluation criteria to individual organizational units we have subdivided our departments into two categories: "Research Departments" and "Technology Departments". Our five Research Departments have specific research aims and carry out basic and applied research work. Their projects have strong roots in contemporary research topics and/or are engaged in the development of methodological tools to advance research in the life sciences. Our three Technology Departments support the research and development work at the Institute. Their work is primarily oriented towards the needs of the Research Departments. At the same time they develop their technology base and accept service and cooperation projects from third parties.

Further information on aims and scientific concepts of the Research and Technology Departments is given in the introductory section of the respective Department.

Hans-Knöll-Institut für Naturstoff-Forschung e.V.
Beutenbergstraße 11a
07745 Jena
Tel: +49 (0)3641 / 65 6611
Fax: +49 (0)3641 / 65 6600

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Further Information: www.hki-jena.de