Supervisor: Ivan Ahel

Poly(ADP-ribose) polymerases (PARPs) are the major family of enzymes that synthesize an abundant posttranslational protein modification called ADP-ribosylation. Through their ability to modify different target proteins and to respond to variety of stimuli, PARPs control genome stability, cell differentiation, metabolism and immune responses. Inherited defects in the protein components of the pathways regulated by PARPs often cause disease in humans such as cancer, immunodeficiencies, neurodegeneration and developmental syndromes. In recent years it has become apparent that using specific drugs to inhibit or modulate protein ADP-ribosylation can be very effective in disease treatment (for example breast, ovarian, pancreatic and prostate cancer). Thus, furthering our knowledge of the protein factors and pathways regulated by PARPs provides a basis for the development of new therapies.

In our laboratory we have recently identified several uncharacterised proteins that regulate PARP activity. The aim of the PhD project will be to elucidate the exact molecular and physiological functions of these proteins, which will also cover the newly identified links with protein stability and degradation. Our laboratory uses a large variety of techniques that will enable us to efficiently and collaboratively study the relevant processes on different levels (protein biochemistry, cell biology and Drosophila melanogaster genetic model, bioinformatics and structural biology).

Publications:

1. Zhu, K., Suskiewicz, M.J., Hloušek-Kasun, A., Meudal, H., Mikoč, A., Aucagne, A., Ahel, D., and Ahel, I. (2022) DELTEX E3 ligases ubiquitylate ADP-ribosyl modification on protein substrates. Science Advances 8, eadd4253.
2. Zhu, K., Chatrin, C., Smith, R., Ahel, D., and Ahel, I.(2025) Interplay between ubiquitination and ADP-ribosylation and the case of dual modification ADPr-Ub. Essays Biochem 69, 267-279.