SCOPE & OBJECTIVES OF FRONTIERS OF FUNCTIONAL GENOMICS

The figure below is an overview of the major areas of functional genomics which come into the scope of the programme, illustrating their integration through bioinformatics and systems biology, and indicating that they impinge directly on human health, environment, industry and society.

High throughput data for genome-wide analysis are obtained using a variety of technologies, followed by computer-based analysis and then integration. Key data areas include: genome wide variation; gene expression at the mRNA and protein levels; protein interactions and organisation in networked pathways; and the effects of modification of gene structure and expression in model organisms. Bioinformatics tools identify function through genome comparisons, predictions, literature mining and modelling, while integration enables interpretation and understanding at the whole cell and organism levels (systems biology). The implications of functional genomics research are particularly important in healthcare, from greater disease understanding to predictions, novel therapies and new opportunities for industry; in addition there are environmental implications, while ethical and legal issues are of increasing public interest and concern. These different aspects define specific areas of focus for the new programme. Building on the success of the ‘Integrated Approaches' programme, this programme takes functional genomics a stage further into systems biology and explores key areas of its applications, particularly in biomedicine.

The first area of focus is on leading-edge technology development in arrays, nanosystems, and gene silencing. Highly sensitive array systems (biochips) are being developed for genotyping, resequencing, transcriptome analysis, protein detection and function, and cell and tissue analysis, while nanosystems will allow for detection and analysis down to the single molecule and single cell levels. Mutational and knockdown strategies, particularly the powerful, recently introduced RNA interference (RNAi), can specifically silence individual genes, the phenotypic effects of which can be observed on a global scale in genetically amenable model organisms or cells. A second focus is on bioinformatics, without which the data cannot be made accessible, organised and understood, and systems biology. The latter, one of the most far-reaching developments in recent years, attempts to understand function not on individual genes or proteins but on multimolecular modules and ever more complex systems. Three levels of genomic analysis - the mRNA level, the protein level, and the level of low molecular weight intermediates (metabolites) - combine to provide an understanding of whole organism functioning. Systems biology aims to describe how the molecular properties of the cell constituents lead to its complex organisation and integrated properties, and beyond that to the predictable development of organs and the organism as a whole.

There is great potential for the human genome sequence information, through the application of new technologies and systems biology, to yield new insights into the pathogenesis of human diseases and new strategies for prevention or treatment. Biomedicine is therefore a third major focus for this programme, from disease understanding to predictive and personalised approaches to treatment and responses to drugs. Functional genomics will increase the understanding of disease mechanisms, and guide the development of new drugs and therapeutic procedures. Areas coming to the fore where technologies are key include epigenetics and epigenomics, which are expanding the understanding of gene regulation and disease, especially in oncology; neurogenomics, which is leading to the assembly of gene expression and function maps in the brain and relating them to neurological disease; metabolomics, in which comprehensive knowledge of metabolic pathways has applications in biomarker discovery and toxicology; and pharmacogenomics, with its implications for personalised medical interventions. Examples of other emerging biomedical topics which we expect to be included during the course of the programme are stem cell genomics and cardiogenomics. In addition, population genomics and epidemiology are a particular European strength which will continue to be an important part of identifying disease genes. Therapeutic as well as economic benefits accrue through the biotechnology and pharmaceutical industries, which utilise the new methods and knowledge to identify novel drug targets.

Genomic analysis also leads to increased appreciation and understanding of the diversity of the environment. The programme will explore means of strengthening efforts to apply post-genomics technologies (e.g. metagenomics) to improving understanding of natural ecosystems and to exploit their capabilities to degrade xenobiotic chemicals and other pollutant products of human activities. Finally, we propose to take into account the interface between advances in functional genomics research and society. Biobanks and populations are now major resources for genome research, which have also raised significant ethical and legal questions. The programme will aid the understanding of risks and promote discussion of the ethical and legal issues to be confronted through public and governmental debate.