Research Topics
Our group investigates the processes of DNA replication and repair, signal transduction, cholesterol metabolism and cell wall biosynthesis in respect to the virulence of tubercle bacilli and as potential targets for the development of new antituberculosis drugs. We use a wide range of genetic, genomic, proteomic and transcriptomic methods applied both in vitro and in vivo. In our studies we routinely employ site- directed mutagenesis based on homologous recombination. We are now in possession of considerable collection of mycobacterial mutants (listed here). Feel free to email me to discuss collaborative research projects.
The first branch of our research are the analyses of host-pathogen interactions. To highlight our achievements, we showed that Mtb is able to accumulate and utilize cholesterol. Further, we showed that cholesterol oxidase ChoD and ketosteroid dehydrogenase KstD are required for the virulence of Mtb during infection, even though ChoD and HsdD were previously shown dispensable for cholesterol degradation in vitro. In a related research we investigated the essentiality of AccD6 carboxyltransferase in pathogenic and non-pathogenic mycobacteria. Finally we identified and described a number of interactions between innate immunity factors (including TLR2, IL-8, SAA, between others) and mycobacteria.
The second branch of our work are studies regarding the nature of DNA replication and repair pathways in mycobacteria. We identified and performed a preliminary screen of DNA metabolism proteins, namely DnaG, RNase HI and ligase A. These proteins, due to their essentiality for mycobacterial cell, may be considered as potential targets for novel antituberculosis drugs. We also showed that non-homologous end joining (NHEJ) and homologous recombination (HR) preferably repair distinct substrates in vivo.
The third main topic of our research is mycobacterial regulation of cell cycle. In collaboration with dr Rajagopalan and dr Madiraju groups we investigated the role and interactions of several cell division related proteins (FtsZ, CwsA, CrgA, Wag31 and others). We are also interested in regulation thru two- component systems with special attention taken to MtrAB, PdtAS and orphan regulators.
Finally we are involved in epidemiological studies of tuberculous and nontuberculous mycobacteria. We have published a number of papers regarding methodology and describing current epidemiologic situation in our local community.
