CORDIS Archive

Area 4 - Cell Communication in Neurosciences

Objectives

The aim is to obtain a clear understanding of the complex aspects of cell physiology and cell communication of the nervous system during development and in the adult by multi-disciplinary studies, including cellular and molecular biology, pharmacology, molecular genetics and biochemistry. This research will provide the basis of an understanding of dysfunctions of the nervous system and tools to develop new therapeutic approaches.

Research Tasks

4.1 Development of the nervous system

A multidisciplinary approach will be taken to understand the cellular and molecular basis of the development of the nervous system (such as cell proliferation, migration, differentiation, neurite outgrowth, synapse formation, apoptosis and myelination).

Such studies should focus on:

• Identification of the genes involved in the different steps during development, including their regulatory development.

and/or

• Identification of molecules involved in development (e.g. growth factors, adhesion molecules, extra-cellular matrix molecules, receptors, hormones, etc), their functions and regulation, their transduction systems and, ultimately, their regulatory effect at the level of transcription factors and gene expression.

Preference will be given to cross-linking studies of these genes and molecules in degenerative and/or regenerative processes in the nervous system.

The development of a database in relation to the projects will be encouraged.

4.2 Regeneration of the nervous system

Research on the cellular and molecular basis of regeneration in the central and peripheric nervous systems, the design of molecules able to trigger regeneration including re-expression of genes involved in neurite outgrowth.

4.3 Degeneration and apoptosis in the nervous system

Studies aiming at elucidating the basic mechanisms, at the cellular and molecular level, which underly degeneration and apoptosis, including the role of glial cells and the immune system. Special attention will be given to bovine spongiform encephalopathy, scrapie, Creutzfeld-Jacob and related diseases.

4.4 Management of information by the nervous cells

Understanding, at the cellular, molecular and up to the system level, the management of information by the nervous cells in relation to specific functions such as learning and memory, movement, nociception, vision, hearing, etc. Attention should be given to intra and intercellular events. Concerning learning and memory, preference will be given to projects which include the studies of these functions during normal ageing. The development of databases in relation to the project will be encouraged.

4.5 Cell to cell communication in the nervous system

Studies should focus on:

• Understanding cell to cell communications. Special attention will be paid to receptors: the study of their distribution and their molecular, pharmacological and functional properties. The design of new drugs targeting these receptors and with potential therapeutic interest will be considered.
• Understanding of the cell biology and the physiology of transport processes across the blood-brain barrier in order to develop effective drug-delivery strategies.

Synergies with other specific programmes

Projects including definite steps towards medical or veterinary applications, such as specific human or animal pathologies related to degenerative diseases or clinical trials of neurodrugs will not be considered in Biotech. They will have to be placed within the Biomedical and Health or the Agriculture and Fisheries research programmes. The establishment of databases will be implemented in collaboration with the Biomedical and Health research programme.

Developments in the fields of neural networks and artificial intelligence will be covered by the Information Technologies programme.

Area 5 - Immunology and Transdisease Vaccinology

5.1 Immunology and immunotechnology

Objectives

Development of new biotechnology-derived substances which may reveal a range of effects preventing and/or controlling major human and animal pathologies:

• in relation to the functioning of the immune system (monoclonal and recombinant antibodies, immunotoxins, cytokines, growth factors, receptors, adhesion molecules, etc)
• pointing to different states or properties of the immune system (antibodies, nucleic acid probes, etc.)

As the scope for applications based on immunology and immunotechnology is steadily increasing through a rapid renewal of our understanding of the immune system, it will be an important element of the appreciation of future proposals that the latest developments in fundamental immunology be incorporated, where applicable, to support novel and original goals.

Research tasks

A multi-disciplinary approach aimed at developing biotechnology-derived substances or techniques in relation to the immune system, capable of preventing or controlling major pathologies like those of cancer, transplantation, autoimmunity, etc. Special attention will be paid to projects including mechanistic studies at the basis of new diagnostic or therapeutic concepts.

5.2 Transdisease vaccinology

Objectives

Molecular biology and recombinant DNA technology have totally modified our knowledge of the antigenic structures of pathogens. Likewise, valuable insights on immune mechanisms have been obtained and great progress has been accomplished in the understanding of host/pathogen interactions. This knowledge must now be used for the development of second generation vaccines which will be more efficient, more economical, safer and easier to deliver. The biosafety problems linked to the new generation of vaccines will be reviewed in close collaboration with area 7.

Research tasks

Research on generic (or transdisease) vaccinology will be encouraged on topics like:

• live carriers, their safety in normal, immunocompromised hosts and in others species likely to be in contact
• nucleic acids
• non-live carriers
• antigen delivery systems
• neonatal and infant immunity in relation to vaccinology
• mucosal immunity in relation to vaccinology
• induction of T and/or B specific immune responses
• definition of T and/or B antigenic epitope characteristics.
• development of new methods concerning immune correlates protection for infectious diseases, in particular in the field of cell-mediated immunity.

Priority will be given to projects aiming to develop vaccines which could be efficient even administered at a single dose. Studies on host-pathogen interactions could be considered as much as they could be judged relevant to vaccine development and not only to a specific human and/or animal disease. Model diseases will be chosen based on their relevance to human or veterinary medicine and the opportunity to address fundamental questions on disease pathogenesis.

Synergies with other specific programmes

Research will preferably be supported where technological developments might have a generic interest for more than one specific vaccine. Projects on specific human or veterinary vaccines would be regarded as better placed within the Biomedical and Health or the Agricultural and Fisheries research programmes.

Area 6 - Structural Biology

6.1 Structure-function relationships

Objectives

The primary scientific and technological objective is the understanding of how the function of biological macromolecules is related to their structure and spatial organisation, and the design of improved biomolecules with the desired properties. Towards this long-term objective, the approach followed in this area will focus on technological means irrespective of the types of molecules or subjects those means will be applicable to.

Flexibility on subjects: a reasonable flexibility will be applied to the choice of biological macromolecules for these investigations, and to the subjects under study. They could, for example, cover protein folding, biocatalysis, membrane proteins, nucleic acids, carbohydrates, RNA, etc. This flexibility aims at mobilizing the scientific community of structural biologists , inviting the most promising and innovative research, and being capable of responding rapidly to the evolution of concepts.

Technological requirements: The following constraints aim at enforcing synergies between different novel aspects of research in structural biology. The invited contributions should be multidisciplinary and systematically combine the three following facets of structural biology:

• experimental determination of threedimensional structures,
• improvement of structure determination techniques and,
• development of biochemical entities with the desired functions.

Research tasks

In view of the flexibility on subjects, and the requirements for technological inputs presented above, the proposals could address a wide spectrum of targets, provided they would address all three following topics to variable degrees (although one topic should become prominent in each proposal):

6.1.1 Three-dimensional structure determination

As the life sciences experts wished to stress, the systematic experimental determination of many more threedimensional structures of biological macromolecules and complexes of macromolecules (such as proteins, DNA, RNA, carbohydrates or lipids) will form the basis of our developing knowledge of the relationships between primary structures and the tertiary structures of biologically active macromolecules and, even more so, the quaternary structures of the multi-subunit complexes which mediate most biological activities. The complementary need to store, retrieve and analyze the rapidly accumulating biomolecule structural information is taken into account in Area 8 (Infrastructures).

6.1.2 Improvement of techniques

The improvement of techniques, such as X-ray diffraction, NMR, mass spectrometry, etc, for experimental 3-D structure determination of biological macromolecules and the growing size of structures that they can assess will allow, for example, better resolution, and work on subcellular structures, with further implications for an understanding of biological functions within the cell. Synergies and complementarities between the different techniques are invited in the proposals. Of particular importance for the improvement of techniques is synchrotron radiation for macromolecular crystallographers which allows more accurate data to be obtained. Because synchrotron radiation facilities are particularly suited to serve multinational interests through collaborative projects, proposals including the cost of operating such facilities would be welcome, particularly when this leads to novel and challenging experiments (e.g. very small crystals and rapid data collection).

6.1.3 Biomolecules with the desired functions

The discovery and refinement of new biochemical entities with desired functions will consider both terms of the following alternatives:

• rational design, including de novo design, of biomolecules with specific structural,chemical or catalytic properties, which requires a detailed understanding of and control over biomolecular conformation and reactivity.
  
  
• in vitro selection technologies of natural or de novo designed structures by their binding or catalytic activities, consisting in a large, heterogeneous pool of biomolecules subjected to multiple rounds of selection and mutation. This includes, for example, display of proteins on the surface of filamentous phage, or in vitro directed molecular evolution to select RNAs with catalytic or affinity properties.

6.2 Interface of structural biology with electronics

Objectives

The emerging interface of biology and electronics will be explored with a view to allow the interplay of competencies in structural biology and micro- and nano-scale engineering towards new possibilities of designing functional units which could incorporate modifications at the scale of the nanometre. In this domain, the invited contributions should in priority reduce the huge gaps which still exist between groups which deal with:

• micro or nano device fabrication in materials and,
• biological systems where structural biology is of key importance.

Research tasks

The systematic combination of groups of material engineers which deal with micro or nano device fabrication, and groups of "bioengineers" which deal with biological molecules is requested in the invited contributions for this research task. Priority will be given to the study of the interface of man-made structures and biological molecules, including the following scientific and technological topics:

6.2.1 Signal transduction

The signal transduction, in particular, electrical and optical signals, between biomolecular functional units and man-made substrate structures, including, for example, direct electron transfer between metals and redox enzymes.

6.2.2 Improvement of experimental tools

The improvement of non-destructive techniques with high spatial and time resolution which, for example, characterise bio-active interfaces (structure, function, stability) and, the design of miniaturized transducers for devices based on biological function.

6.2.3 Research on new applications

The molecular nanostructure engineering, combining nanotechnology and biosystems, will be explored in order to lead to new generations of applications. Here, the task is not to develop a specific application or product but rather to acquire the basic understanding necessary to detect and highlight new opportunities for applications which can emerge from the following symbiosis between biosystems and nanotechnology:

• biological molecules present properties (for example, the tendency to self-assemble into highly organized two- and three-dimensional structures) which are highly attractive in today's drive for new engineering materials and,
  
  
• nanotechnology offers new tools to study biological molecules, to perform micro-scale biochemistry, to manipulate cell components and to render macromolecular structures able to controlling their activities or function (for example, in the field of biosensors).