진학프로석·박사 채용 접수 플랫폼

Department of Neurotoxicology, Mossakowski Medical Research Institute Polish Academy of Sciences is recruiting a Postdoctoral Researcher to the NCN OPUS 30 project entitled „New 1,3,4-thiadiazole derivatives in glioblastoma therapy - assessment of the activity and revealing the mechanism of action" (2025/59/B/NZ7/01715)

Supervisors: Dr. Monika Szeliga and Dr. Piotr Lipiński

Summary of the project: Glioblastoma (GBM) is the most common and aggressive malignant brain tumor with a dismal prognosis. Intratumor heterogeneity of molecular genetic profiles in GBM may underlie differences in patient sensitivity to therapy. Furthermore, male sex is associated with both higher incidence of GBM and poorer survival outcomes. Thiadiazole is a heterocyclic compound containing one sulphur and two nitrogen atoms. It occurs in several isoforms, of which 1,3,4-thiadiazole is the most widely studied. Our initial screening studies enabled the selection of four novel 1,3,4-thiadiazole derivatives that display anticancer activity against GBM cells and are relatively less toxic towards human astrocytes. Particular GBM cell lines used in this screening present differential sensitivity to the tested compounds, which reflects the aforementioned heterogeneity of GBM involving, among others, divergent response to treatment. These preliminary results, along with literature data, indicate that all four 1,3,4-thiadiazole derivatives deserve further investigation. As a part of this interdisciplinary project we will analyze the activity of these compounds in primary human GBM cells stratified according to their transcriptomic subtype and derived from patients of different sex. Subsequently, we will decipher the molecular target or at least the mechanism of action of the most promising compound. To this end, we will examine the influence of this compound on the transcriptome, proteome, and metabolome of GBM cells. Multiomics, an approach that combines data from different molecular levels (transcripts, proteins, metabolites), aided by in silico target prediction, will enable us to uncover putative target of the compound, which will then be validated functionally using a broad range of biochemical and biological techniques.

The research tasks will include:

▪ To design and synthesize new thiadiazole derivatives based on biological results, structure–activity relationships, physicochemical properties, and predicted target interactions;

▪ To design and execute efficient, reproducible synthetic routes for the preparation of the selected compounds and their analogues;

▪ To purify synthesized compounds and perform their complete structural and analytical characterization;

▪ To prepare and manage compound stocks, reference materials, analytical samples, and compound documentation;

▪ To coordinate or participate in the evaluation of in vitro ADME/DMPK properties, including metabolic and plasma stability, permeability, protein binding, and CYP-related liabilities;

▪ To perform in silico target fishing, molecular docking, and the interpretation of predicted compound–target interactions;

▪ To perform biochemical tests to validate the molecular target and mechanism of action of the lead compound;

▪ To prepare experimental reports, presentations, figures, and chemistry sections of scientific publications;

▪ To support a PhD student.