Project information
How are drug-metabolizing enzymes regulated in parasitic nematodes? (NEMADME)

As the drug resistance developed by parasitic nematodes has become a worldwide problem, understanding the precise mechanisms behind this process has become a crucial concern in parasitological research. In previous studies, the project team has revealed that increased glycosylation and efflux of anthelmintics in resistant nematodes improves their tolerance to the drug. Furthermore, the contact of nematodes with anthelmintics induces the expression and activity of certain drug metabolizing enzymes (DME) e.g. UDP-glycosyl transferases (UGTs), and efflux transporter e.g. P-glycoproteins (Pgps). The reasons why DME genes are constitutively upregulated and which mechanisms are responsible for their induction are yet to be determined. Therefore, in the frame of this project, we would like to contribute to a better understanding of these processes. We will focus on the regulatory regions of DMEs (e.g., proximal promoters) to uncover whether the particular transcription factors (TFs), such as nuclear hormone receptors (NHRs), and/or endogenous ligands (ELs) are involved in their transcriptional regulation. We will also assess whether epigenetic determinants like DNA methylations can be involved in the altered transcription of DMEs related to anthelmintic resistance. New insights into regulation of DMEs may open novel research avenues in exploring the mechanisms which drive anthelmintic resistance. In addition, this knowledge can contribute to the search for new anthelmintics that are essentially needed.