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 

Investigating the role of Hexose-6-Phosphate Dehydrogenase (H6PD) deficiency in Skeletal Myopathy and metabolic dysfunction

The MolSysTox group at the University of Basel is offering a Master’s thesis project focused on investigating the role of Hexose-6-phosphate Dehydrogenase (H6PD) deficiency in the onset of skeletal myopathy and the associated inflammatory response. The study will utilize transgenic H6PD knockout models and murine cell lines.

H6PD is an enzyme localized within the lumen of the endoplasmic reticulum (ER), where it catalyzes the first two reactions of the pentose phosphate pathway. Specifically, H6PD facilitates the oxidation of glucose-6-phosphate to 6-phospho-gluconolactone, generating NADPH in the process. This enzymatic activity is crucial for maintaining the redox balance within the ER and supports various cellular activities such as lipid synthesis and proper protein folding.

The Master’s thesis project will employ a comprehensive experimental approach to assess the impact of H6PD ablation on skeletal muscle function and the inflammatory response. The research aims to uncover novel insights into the molecular mechanisms by which H6PD-associated metabolic dysfunction may contribute to inflammation and fibrosis in skeletal muscles and other organs. The findings of the study may have important implications for the development of therapeutic strategies targeting muscle repair and metabolic disorders.

Methodology:

Throughout this Master’s thesis, you will actively learn and apply essential life science techniques, gaining valuable hands-on experience and developing key skills, including but not limited to:

• Cell culture: Handling and maintaining murine muscle, and immune cells, performing co-culture assays
• Gene expression analysis: Extracting RNA and performing qPCR to understand gene regulation in metabolic pathways
• Protein analysis: Isolation of proteins and conducting western blot to investigate muscle atrophy and dysregulated metabolic pathways, and fibrotic markers
• Histological analysis & Immunostaining: Staining and visualizing muscle fibers, and identifying fiber types
• Immunological assays: Usingflow cytometry and ELISA to check cytokine levels
• Data analysis & experimental design: Developing statistical skills, planning, conducting, and analyzing in vitro experiments

Candidate requirements:

We are seeking a motivated master’s student with:

• A background in pharmaceutical sciences, molecular biology, or a related field
• Prior experience with cell culture and molecular biology techniques (preferred but not required)
• Willingness to learn and develop new technical skills
• Excellent analytical skills and keen attention to detail
• A strong interest in immunometabolism research and potential clinical applications
• Effective communication skills in English 

Dr. Madhuri Manivannan,

Dept of Pharmaceutical Sciences, Molecular and Systems Toxicology

no

yes

Workplace in Rosental, Mattenstrasse in Kleinbasel