Personal information

Hint, Fhit, HIT proteins, H2S, H2Se, nucleotides, enzymes, reductive stress, redox homeostasis
Poland

Biography

In 1987 I joined prof. Wojciech Stec’s group at the Department of Bioorganic Chemistry, Center for Molecular and Macromolecular Studies Polish Academy of Sciences (DepBioChem CBMM PAS) in Lodz. At that time, I was introduced to modern methods used in chemistry, e.g. work at super anhydrous conditions, HPLC, electrophoresis, solid-phase oligonucleotide synthesis. At the same time, I was involved in the mainstream research associated with the chemical synthesis of oligonucleotides and their thiophosphate analogs.
As part of my doctoral dissertation work, I synthesized the phosphorothioate oligonucleotide (PS-oligo) analogs (15-mer) containing all the internucleotide bonds with defined Rp (all-Rp) or Sp (all-Sp) configurations. Next, I used these compounds to study the influence of phosphorothioate internucleotide bonds stereochemistry on activity of enzymes, RNase H (from E. coli) and two reverse transcriptase (RT): avian leukemia virus (AMV RT) and human immunodeficiency virus (HIV-1 RT). The results of the research included in the dissertation were published in three original papers and one review article.
In the years 2002-2003 I held a postdoctoral training in the team of Professor Charles Brenner (Philadelphia, USA). I was involved in biochemical research of selected enzymes from the histidine triad family (HIT), e.g. Hint1, Hint2, Fhit, Dcp1. At that time, I gained experience at the expression and isolation of proteins in various bacterial systems (including enzymes very sensitive to deactivation), as well as I learned the basics of crystallography.
After returning from the postdoctoral training, the experience gained during the realization the above tasks became the basis for partially independent research conducted at DepBioChem CMMS PAS. I continued researching on HIT proteins topic in the context of the interests and opportunities offered by DepBioChem. So my research were focuses on combining my knowledge at area of enzymology and biochemistry with the utility of phosphorothioate analogs of nucleotides and oligonucleotides, in particular those with stereo-defined absolute configuration. Research on the enzymatic activity and mechanism of Hint1 and Fhit enzymes, described in a series of six publications, comprise the basis of the habilitation application. My research objectives included determining the mechanism of Hint1 catalyzed hydrolysis of P-N bond and investigating the mechanism of Hint1 desulfurization of (d)NMPS to (d)NMP (release of H2S was shown) under in vitro conditions and in cellular tissues.