The research program focuses on rare diseases and on elucidating the role of rare genetic variants in the development of complex diseases across clinical cohorts collected and characterized by clinical partners.
The methodological foundation is provided by the Research Unit for Rare Diseases (Prof. Kmoch) at KPDPM, which is also a founding and integrating part of the National Center for Medical Genomics (NCMG; www.ncmg.cz).
Through this infrastructure, the group provides expertise and access to state-of-the-art methods for the analysis of human genetic information and model organisms to numerous partners in the Czech Republic and internationally.
Additional unique expertise is contributed by:
- Bioinformatics team (Stránecký, Přistoupilová, Zemánková, Nehasil, Mušálková, Řeboun): analysis of a broad spectrum of multi-omics data.
- Comparative pathology group (MUDr. Sikora): investigation of cellular, tissue and organ pathology in rare diseases using human samples and mouse models.
- Proteomics and metabolomics group (Ing. Hnízda, Mgr. Kuchař): monitoring protein and metabolite changes in body fluids, cell cultures, patient tissues and model organisms.
- Laboratory specialists (Mgr. Dobrovolný): advanced tissue culture work, including preparation and targeted differentiation of induced pluripotent stem cells and organoids; development and characterization of model organisms (C. elegans, Drosophila, zebrafish, mice) in collaboration with the Czech Center for Phenogenomics.
- Mitolab team (Hansíková, Štufková, Vanišová, Rákosníková): functional characterization of cellular bioenergetics in primary and secondary mitochondrial disorders.
- CDG team at Mitolab (Dr. Hansíková, Dr. Ondrušková): application of innovative methodological approaches to study the pathobiochemical mechanisms of glycosylation disorders.
- Medicinal Chemistry Group (Assoc. Prof. Jakubek, Prof. Martásek): coordination of chemical screening activities integrating computational, organic and analytical chemistry with biochemistry and molecular biology; collaboration with CZ-OPENSCREEN and international partners to advance research on rare diseases and bioactive compounds.
The translation of findings into clinical practice will be coordinated with relevant organizational units of Charles University, including the Center for Knowledge and Technology Transfer and the university’s spin-off, Charles University Innovations Prague.
Modern biomedical research relies on intensive collaboration between clinical departments and laboratories. Beyond traditional methods, approaches that integrate clinical and biological data, bioinformatics, imaging analysis, and artificial intelligence are increasingly important.
The proposed program aims to provide scientific training to motivated young clinical and laboratory researchers, enabling their active engagement in interdisciplinary collaboration across participating units. This will expand methodological and expert capacity and enhance the quality of clinical, research, and educational activities.
Expected outputs include elucidation of genetic, molecular, and cellular pathological mechanisms underlying the studied rare diseases; new insights into the biological functions of causal genes and gene products; and understanding of the structure and regulation of relevant metabolic, regulatory, and signaling pathways.
These results will advance knowledge of fundamental developmental and pathophysiological processes in human cells and tissues and help define candidate genes and pathophysiological processes involved in complex diseases. Additional outputs will include the development of new diagnostic methods, identification of therapeutic targets, and discovery of molecules or biological procedures for further biomedical research or drug development.
The project is therefore expected to generate novel, broadly applicable insights relevant to multiple medical specialties and fundamental biomedical research.
The research teams involved in the proposed program have demonstrable translational potential. Many results have been and will continue to be applied in the form of new clinical procedures, laboratory diagnostics, and potentially commercial applications.
Outputs with commercial potential will be protected by patents or trademarks and licensed to industry partners.