Since 1972 the former Institute for Immunology of Purkyne Military Medical Academy has been engaged in the study of pathogenesis of severe viral, rickettsial and bacterial infections. In the late eighties this Institute built laboratory for the analysis of complex protein mixtures originating from prokaryotic and eukaryotic cells that was based on the application of high resolution two-dimensional gel electrophoresis (2-DE). After the reconstruction of the Institute in 1994 the whole research activities focused on the study of intracellular parasitism of bacteria using Francisella tularensis LVS as the model of experimental bacterial infection. Furthermore, the complete proteome technology, including computer-assisted 2-DE gel evaluation and MALDI-TOF MS for protein identification, was successfully implemented. In 2000 the institute launched the tight cooperation with Faculty of Medicine of Charles University in Hradec Kralove and Masaryk Memorial Cancer Institute in Brno in order to perform the complex analysis of host-bacteria interactions on tissue, cellular, protein, and nucleic acid level. For this purpose the Proteome Center for the Study of Intracellular Parasitism of Bacteria, involving selected scientists from all three Institutions and fully supported by the 5 years grant from Ministry of Education, Youth and Sport, was founded.

Aims of the project:

1. To establish specialized interdisciplinary Center for the study of intracellular parasitism of bacteria which represents therapeutically uncontrollable source of serious illnesses of human mankind.
2. To establish educational Center for realization of Doctor Study Programs (Ph.D.) on the basis of laboratories that utilize a complex of advanced laboratory technologies for bio-medical research.
3. To understand the molecular basis of intracellular parasitism of bacteria.

1. Complete proteome database of microorganisms with highlighted virulence factors, proteins with diagnostic value and immuno-dominant proteins. The identification of these groups of microbial markers should enable the construction of more sophisticated diagnostic, prophylactic, and probably therapeutic tools.
2. Complex dynamic proteome, morphological, phenotypic, and metabolic studies of primary intracellular bacteria – host cell interaction that will assist in understanding of processes underlying the final outcome of this interaction. This study will provide a detailed information on gene expression, including post-translational modifications of proteins, time-course, spatial expression and co-expression of microbial and host molecular markers and signals that induce expression of these markers.
3. Comparative analysis of model and clinical parameters of infection induced by intracellular bacterial pathogens.

Rationale of the project and expected impact to R&D:

1. The connection of individual top specialized laboratories of several institutions that are oriented to partial analysis of different bio-medical systems into efficient research Center that capable to perform complex studies in molecular physiology and molecular pathology.
2. The Center enables the Czech science to join the rapidly expanding area of Proteome and Proteomics studies.
3. The foundation of the Center assists in coordination of research studies oriented to serious infection diseases in the fields of microbiology, immunology, molecular biology and pathology.
4. A more frequent exchange of scientists among labs, grouped in the Center on one side, and a higher number of Ph.D. students and post-doc fellowships on the other side, are expected to occur after the Center foundation.
5. The combination of Genome and Proteome analysis with parallel morphological and metabolic studies and the evaluation of results by gnostic and multivariate statistical methods will bring very quickly new knowledge concerning the co-existence of microbes and host organisms.
6. Regarding the development the outputs in the form of identified markers of microbes utilizable either for efficient prophylaxis or for construction of diagnostic sets will be provided. The outputs from the research of patho-physiology of infected cells will also be useful for the selection and development of quite new or re-oriented pharmaceuticals.