Research Interests:
Bacteria are the dominant form of life on Earth. We are interested in molecular mechanisms and strategies that bacteria have evolved to cope with various environments. Our laboratory uses several model bacteria, namely Bacillus subtilis, a Gram-positive soil bacterium that can undergo the developmental process of sporulation; Mycobacterium smegmatis, a non-pathogenic relative of the human pathogen M. tuberculosis; andEscherichia coli, a model Gram-negative bacterium. Also, we have projects running that are focused on applied research.
Our current projects include:
- We study promoter DNA sequence. We investigate how the promoter DNA sequence affects regulation by small molecule effectors, such as initiating nucleoside triphosphates and coenzymes (e. g. NAD+).
- We study subunits of RNAP/factors associated with RNAP that are specific for Gram-positive bacteria. The aim is to characterize the role of these factors in regulation of gene expression in the context of RNAP. On these projects, we collaborate with structural biologists (NMR, crystallography, single particle analysis)
- We study small RNAs, namely 6S RNA that is vital for regulation of gene expression in stationary phase of growth. Recently, we discoverd a novel small RNA in Mycobacterium smegmatis (Ms1) and we are investigating its function.
- We study mechanisms of bacterial resistance to antibiotics.
In collaboration with other teams (Institute of Organic Chemistry, Prague; Faculty of Mathematics and Physics of Charles University, Prague; 2nd Faculty of Medicine, Motol; TRIOS a. s.) we are developing novel structures with antibacterial activity. The primary target of these molecules is RNAP but we have also developed antibacterial compounds acting on other targets.The latter compounds, termed lipophosphonoxins, display promising activities against a range of bacterial strains, including strains resistant to existing antibiotics. Importantly, lipohposphonoxins are not toxic to human cell lines. Projects are under way to develop these compounds into marketable products.