Our research focus is molecular mechanisms and evolution of ribosomal protein synthesis and its regulation. The lab is using a combination of biochemical, microbiological and next-generation sequencing approaches and supported by collaboration with structural and evolutionary biologists to tackle three highly complementary research directions:
- Structure-functional studies of ribosome-associated and ribosome-independent enzymes RelA-SpoT Homologue (RSH) enzymes controlling intracellular levels of alarmone nucleotide (p)ppGpp in bacteria. The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, antibiotic tolerance and pathogenicity. Since the stringent response is central to bacterial physiology and plays a crucial role in virulence and antibiotic tolerance, its specific inhibition by small molecules is an exciting novel strategy for disarming and pacifying bacterial pathogens. To uncover the molecular mechanisms of the stringent response and develop specific inhibitors, our lab is using an array of biochemical (enzymatic assays with reconstituted translation system, EMSA, DRaCALA, analytical gelfiltration and HPLC analysis of nucleotide pools), microbiological (bacterial genetics, antibiotic killing assays) and chemical biology (high-throughput drug screening) techniques.
- Structure-functional studies of bacterial ABCF ATPases involved in translational regulation and antibiotic resistance. Antibiotic resistance proteins in the ABC (ATP-binding cassette) superfamily of ATPases commonly confer resistance by pumping the drug out of the cell. However, the crucial component of the classical ABC pump, the transmembrane domain is absent in ABCF family antibiotic resistance (ABCF ARE) factors. ABCF AREs protect from several chemically unrelated antibiotic classes – macrolides, streptogramin A and lincosamide (MLSA) – that all bind the same target, the peptidyl transferase center (PTC) of the ribosome. The chemical unrelatedness and the common target prompted a hypothesis that AREs directly interact with the ribosome to displace the drug. This hypothesis has recently been experimentally substantiated both for S. aureus VgaA and E. faecalis LsaA. This initial discovery has set the stage for our lab dissecting the system biochemically using reconstituted S. aureus translational system.
- Structure-functional studies of eukaryotic ABCF ATPase translation factors with a special focus on yeast Saccharomyces cerevisiae. ABCF ATPase are also involved in eukaryotic translation. Based on biochemical experiments, S. cerevisiae ABCF eEF3 (eukaryotic Elongation Factor 3) has been suggested to play a role in and ribosome recycling, although its primary function has not been established previously. To uncover the cellular function of eEF3 and other yeast ribosomal ABCFs our lab is using a combination of yeast genetics, ribosome profiling and translational assays in yeast lysates.
If you are interested in joining the lab for a MSci or PhD, please contact the PI directly (vasili.hauryliuk [ät] ut.ee). Please attach to you letter a short CV and a cover letter detailing why you want to join us and motivating why we should take you on. Before drafting the cover letter, please familiarize yourself with our recent publications.
See full list of publications here.
Pavel Kudrin (allkey [ät] ut.ee)
Sofia Raquel Alves Oliveira
Vasili Hauryliuk, senior research fellow
vasili.hauryiliuk [ät] ut.ee