The objective of the BioSapiens Network of Excellence is to provide a large-scale effort to annotate human genome using both informatics tools and input from experimentalists. The Network will create a European Virtual Institute for Genome Annotation, bringing together many of the best laboratories in Europe. This institute will help to improve bioinformatics research in Europe and encourage cooperation between various laboratories.
The BioSapiens network tries also to integrate experimentalists and bioinformaticians, through a directed programme of genome analysis, focused on specific biological problems. The annotations generated by the Institute will be available in the public domain and easily accessible on the web. This will be achieved initially through a distributed annotation system (DAS), which will evolve to take advantage of new developments in the GRID.
The Institute will establish a permanent European School of Bioinformatics, to train bioinformaticians and to encourage best practise in the exploitation of genome annotation data for biologists. The courses and meetings will be open to all scientists throughout Europe, and available at all levels, from basic courses for experimentalists to more advanced training for experts. The BioSapiens NoE will increase European competitiveness, by new discoveries, increased integration, expert training and improved tools and services, and enhance Europe’s role in the academic and industrial exploitation of genomics.
Genome scale analysis of the immune response against pathogenic micro-organisms; identification of diagnostic markers, vaccine candidates and development of an integrated micro array platform for clinical investigations.
The genome sequences of microbial organisms responsible for diseases of world-wide medical importance have been sequenced or will be available in the near future. Technologies for producing large numbers of proteins have been developed and high-throughput assays such as protein micro arrays have been clinically validated for detecting the presence of antibodies, in serum, directed against microbial antigens. These achievements offer the opportunity of investigating the natural immune response against the whole proteome of a variety of micro-organisms. Powerful combinations of genomic information, molecular tools and immunological assays are becoming available to help identify the antigens that function as targets of protective immunity or could be used as markers for serodiagnosis. We propose here to identify in micro-organisms of great medical relevance (M. pneumoniae, C. pneumoniae, L. pneumophila, coronavirus spp and P. falciparum), a large collection of surface and secreted proteins as well as putative endotoxins. This protein repertoire will be produced as recombinant molecules or as sets of overlapping synthetic peptides and printed on array slides. The serum reactivity of groups of individuals with proven history of exposure to the selected micro-organisms will be analysed against the arrayed proteins to identify diagnostic markers and correlates of protection.
This project will significantly expand the SMEs bank of Intellectual Property and contribute to expertise within the RTDs. It is anticipated that the proposed work in high throughput protein expression, software analysis, surface peptides synthesis, protein and peptide surface capture, and array reader instrumentation will create an integrated platform of great commercial and research value. Finally it will contribute to unravelling how the humoral immune response interacts with the microbial proteomes thus filling the gap between genomic data and development of novel vaccines and diagnostic tools.
The main goal of this project is to develop an innovative fusion protein (immunotoxin) for liver cancer treatment, with focus to Hepatocellular carcinoma (HCC). Liver cancer, primarily HCC, is the fourth leading cause of death from cancer. Proposed immunotoxins will be directed to the highly selective antigens on the tumor cells. The project assumes usage of designed fusion proteins comprised of highly selective cancer antibody fragments attached to cytotoxic domains. We plan to create immunotoxins containing cytotoxic moieties derived from catalytic domains of Pseudomonas aeruginosa exotoxin A and diphteria toxin. One of the innovative aspects of the project is the change in immunotoxins subcellular route within human cells. This modification will be a key factor regulating an immunotoxin activity dependently on cell proliferation rate, thus making toxin even more selective anti-cancer drug. The project is conducted in collaboration with the Warsaw University (CeNT) and the Institute of Medical Biology of PAS. As a result, innovative immunotoxins will be patented and commercialized in the further.
Genetically Modified Microbes (GMM) are a biotechnological alternative to different environmental problems such as remediation of polluted sites, where microbes with recombinant catabolic pathways are envisaged as the solution for removal of toxic organic compounds. Moreover, the exploration and exploitation of synergistic interactions between plants and microbes for phytoremediation is also a target to solve contamination problems. Critical to the safe application of recombinant microbes in the environment, and re-assurance of public concerns, is adequate information on safety-related properties of the microbes in question. Current whole genome sequencing efforts on relevant microbes provide a unique opportunity to extract completely new safety-related information, to conduct experiments to generate important new data, and to create new tools for increasing the degree of predictability of the behaviour of strains designed for applications in the open environment or in industrial bioreactors.
One of the microorganisms with current applications in Biotechnology is Pseudomonas putida, a paradigm of metabolically versatile microorganism which recycles organic wastes in aerobic compartments of the environment, and thereby plays a key role in the maintenance of environmental quality. The strain KT2440 is the most extensively characterised and best understood strain of P. putida. KT2440 is a nonpathogenic bacterium certified in 1981 by the Recombinant DNA Advisory Committee (RAC) of the United States National Institutes of Health as the host strain of the first Host-Vector Biosafety (HV1) system for gene cloning in Gram negative soil bacteria. Since then, KT2440 has been used world-wide as host of choice for environmental applications involving expression of cloned genes. This strain is one of the few nonpathogenic microbes which are subject to whole genome sequencing by a P. putida genome project currently in progress in Germany. The sequence data generated in the genome project is being made public at appropriate intervals (a 10-fold genome equivalent of raw sequence data is already available) and will constitute an invaluable resource for this project. Therefore, this microorganism, its recombinant derivatives and the body of knowledge accumulated in the last 20 years on its genetics, physiology and biochemistry make it an ideal and friendly microbe for safe biotechnological applications in the environment.
The major aim of this project is to settle the basis to reduce in a rational, environmentally friendly, and safe manner our contamination problems by developing P. putida strains useful to design environmental treatment systems in harmony with the biosphere.