Impact of azole antifungal agents on steroid biosynthesis in H295R adrenal carcinoma cells

The MolSysTox group at the University of Basel is offering a Master’s thesis to investigate how azole antifungal agents impact steroid biosynthesis in H295R adrenal carcinoma cells.
Azole antifungals inhibit fungal cytochrome P450 enzyme (CYP51) to inhibit ergosterol synthesis, which is needed for cell wall function. However, they can cause adverse health effects by interfering with human steroidogenic CYPs involved in steroid production. This project will examine such effects in H295R cells, a model for adrenal steroidogenesis.

Methodology – What You Will Learn
During this Master's thesis, you will gain hands-on experience with fundamental techniques used in life science research, equipping you with valuable skills in:

• Cell Culture Techniques: Handle and maintain cell lines
• Staining & Imaging Analysis: Visualize cellular structures and biomarkers
• Gene Expression Analysis: Perform quantitative assessments of gene expression to understand gene regulation in biosynthetic pathways.
• Metabolomics: Assess enzymatic activity by analyzing substrate-to-product ratios using data from LC-MS/MS. Depending on progress, you will actively prepare samples and support data evaluation, gaining insight into metabolic profiling.
• Radioactive Tracer Studies: Alternatively, explore enzymatic activity by tracing steroid biosynthesis pathways with radiolabeled substrates, providing a unique perspective on metabolic flux.

Candidate Requirements:

• Background in pharmaceutical sciences, biochemistry, molecular biology, or a related field.
• Experience with cell culture and molecular biology techniques is advantageous but not necessary
• Strong analytical skills and attention to detail.
• Motivation to contribute to toxicological research with clinical relevance.

Application Process:

Interested candidates are invited to submit the following documents:

• A cover letter detailing your motivation and relevant experience (MAX 1 PAGE)
• Curriculum vitae (MAX 2 PAGES).
• Current academic transcript (grades)

Philipp Späne

yes

yes

This work will be conducted in the laboratory of Molecular and Systems Toxicology, University of Basel.

Please send your application to p.spaene@unibas.ch

Selectivity modeling of fungicides inhibiting cytochrome P450 enzymes   

Several Cytochrome P450 (CYP) enzymes play a role in steroid hormone synthesis, e.g. aromatase or aldosterone synthase. They can be potently inhibited by fungicides containing azole moieties, thereby potentially interfering with hormone homeostasis. However, the selectivity of CYP inhibition and the respective binding modes of the inhibitors are still poorly understood. This master thesis aims to rationalize the selectivity of CYP inhibition using computational approaches such as pharmacophore modeling and docking studies. The results could help to understand and possibly avoid unintentional CYP inhibition by future fungicides.

Contact: daniela.schuster@clutterpmu.ac.at  Tel: 0699/14420025

Univ.-Prof. Daniela Schuster

Paracelsus Medizinische Privatuniversität

Leiterin Abteilung Pharmazeutische und Medizinische Chemie

Strubergasse 21, 5020 Salzburg, Österreich 

Dihydrochalcones as multi-target anti-inflammatory and anti-cancer targets: SAR modeling on selected targets    

Dihydrochalcones are natural products with multiple biological activities. For example, they have been shown to act on anti-inflammatory and anti-prostate-cancer targets. This multi-target activity could be an attractive strategy to combat multi-factorial diseases such as cancer in the future. In this project, computational approaches such as docking and pharmacophore-based screening will be used to rationalize the activity data of a series of dihydrochalcones against several targets and to propose improved compounds for future synthesis.

Contact: daniela.schuster@clutterpmu.ac.at Tel: 0699/14420025

Univ.-Prof. Daniela Schuster

Paracelsus Medizinische Privatuniversität

Leiterin Abteilung Pharmazeutische und Medizinische Chemie Strubergasse 21, 5020  Salzburg, Österreich