At the Institute of Organic Chemistry and Biochemistry of the CAS / IOCB Prague, we are looking for talented, independent, and highly motivated PhD students with an MSc. degree or equivalent in life sciences or related fields. We are offering more than 20 new exciting projects in organic and medicinal chemistry, biochemistry, molecular biology, analytical, and physical chemistry.

  • Online registration deadline: 20 February 2023
  • Interview Day: 23 March 2023

Learn more and apply at https://www.uochb.cz/en/call-for-phd-applications

XNA (xenobiotic nucleic acids) are modified artificial analogues of biopolymers orthogonal to natural nucleic acids (DNA or RNA). They mostly contain modified sugar part that makes them resistant to cleavage by nucleases and enables unique secondary folds. Natural DNA or RNA polymerases typically do not tolerate dual base- and sugar-modified nucleoside triphosphates (XTPs) as substrates which seriously limits the application of the XNA methodology. To this end, we propose a project that aims at the in vitro evolution of engineered XNA polymerases to enable efficient enzymatic synthesis of base-modified XNAs from modified XTPs bearing a portfolio of useful modifications. We will use best performing exonuclease-deficient Thermococcus gorgonarius (Tgo) polymerase variants as a platform for mutant library generation using transposon-directed mutagenesis and targeted mutagenesis. Having the library in hands, we will adopt established methods for directed evolution, e.g. phage display or emulsion-based selections. The ultimate and groundbreaking goal would be to develop a polymerase capable of robust synthesis of longer sequences of dual base- and sugar-modified XNA using full set of all-four-base-modified XTP building blocks. However, even a polymerase capable of incorporation of several base-modified nucleotides would be very desirable.

University: Faculty of Science, Charles University
Field of study: Cellular and molecular biology
Tutor: Prof. Ing. Michal Hocek, PhD. DSc.
Group: Michal Hocek Group – Bioorganic and Medicinal Chemistry of Nucleic Acids