Our current research is focused on human proteins with non-canonical RNA-binding domains.
We are especially interested in mitochondrial proteins , since the mitochondrion is an essential organelle that is the main source of ATP and has fundamental roles in all aspects of cell biology, ranging from cell death to growth, differentiation and inflammation. Unsurprisingly, mitochondrial malfunction is associated with a plethora of diseases including cancer, diabetes, neurodegenerative diseases and inflammatory disorders. Proteins which are involved in pathological processes constitute therapy targets and their structures may be used in drug design. In addition, mitochondrion is an intriguing study subject due to its origin in endosymbiosis of a prokaryotic ancestor. Mitochondrial proteins often combine elements of the prokaryotic and eukaryotic worlds or offer an opportunity to discover new protein architectures. One such intriguing group of proteins is the Fas-activated serine/threonine kinase (FASTK) family which participates in the regulation of mitochondrial RNA metabolism. FASTK family members contain putative novel RNA-binding domains of unknown structure, including a potentially new type of helical repeats. Due to its involvement in the alternative splicing of Fas mRNA, FASTK is also a putative target for anti-inflammatory therapeuticals. Once the structure of FASTK becomes available, it may enable us to design drugs against this protein which could help treat asthma or rheumathoid arthritis.*
Our additional topic of interest are the Interferon-induced proteins with tetratricopeptide repeats (IFIT). IFITs are antiviral proteins which are expressed in vertebrate cells in response to viral infection, where they act as innate immune effectors that sequester viral transcripts and inhibit their translation. Building on the previous work on the structure and interactions of human IFITs , we investigate the structure and function of higher order IFIT complexes and their specificity for RNA. We hope to elucidate further the mode of RNA recognition by IFITs and their interplay with the cellular machinery in antiviral defense, as well as to find some medical applications of IFITs in diagnostics of infectious diseases.