PhD student position: Find new and unconventional antibacterial compounds to treat Tuberculosis

PhD student position: Find new and unconventional antibacterial compounds to treat Tuberculosis

100%, starting date 01.01.2023

The Zampieri group offers multiple research opportunities for PhD candidates in the context of systems pharmacology, cancer and microbiology, computational biology and metabolic regulation. These positions will be based in the Department of Biomedicine (https://biomedizin.unibas.ch/en/) in Basel, one of the world's leading locations for life sciences, home to several companies and institutions.
The mission of the group is to understand fundamental mechanisms regulating short- and long-term metabolic adaptation to genetic and chemical perturbations to find new and unconventional therapeutic strategies, ranging from antibacterial to anticancer drugs. To this end, we develop new ways to combine state-of-the-art technologies in metabolomics with mathematical modeling.
The PhD students will exploit some of the cutting-edge experimental and computational methods, comprising high-throughput metabolomics, time-lapse microscopy, constraint-based and kinetic modeling, to investigate how to pharmacologically interfere with fundamental mechanisms in the regulation of metabolism. Available resources at the department include a mouse facility, high-end FACS, IT and microscopy facilities, the Life Sciences Training Facility (for gene expression and proteome profiling) and much more.
The candidates are expected to have a strong background and interest in quantitative disciplines, excellent teamwork and communication skills in English. They will have the opportunity to develop the following projects with a lot of academic freedom and strong support from senior members in the lab, and at the same time to play an active role in shaping and in creating inspiring research and working environment.

We are looking for a highly motivated doctoral researcher to find new and unconventional antibacterial compounds to treat Tuberculosis. This project will be conducted in collaboration with Prof. Michael Berney (https://www.berneylab.org/) at the Albert Einstein College of Medicine (50% wet lab and 50% computational).

Your position

• Using existing experimental protocols for the high-throughput metabolomics analysis of chemically and genetically perturbed M. tuberculosis strains.
• Profiling a large library of small molecules with attractive antituberculosis properties
• Determining the underlying drug modes of action.
• Testing their relevance in host-like environmental conditions
• Support and preparation of scientific reports and journal articles

Your profile

Essential:

• Master's degree in (Bio)Physics, (Bio)engineering, Biological Sciences, Microbiology, Biochemistry, Systems Biology, Molecular Biology, Bioinformatics/Computational Biology, or related fields.
• Basic experience of designing and running experiments with microbial cultures in the laboratory
• Experience with and/or motivation to learn programming language (e.g. Matlab, R or Python)
• Hands-on experience with key biochemical and molecular biological methods
• Motivation to work in an international research environment

Highly desirable:

• Experience with and/or motivation to learn systems biology approaches, high-throughput methodologies, analysis of single cells imaging data
• Good communication skills

Any of the following will be a plus:

• Proficiency in data analysis using Matlab, R or Python
• Interest in mathematical modeling of metabolic and regulatory/signaling network

We offer you

• You will have access to state-of-the-art research equipment in metabolomics, cell biology, time-lapse microscopy.
• You will work in a dynamic and highly interdisciplinary team including computer scientists, experimentalists.
• You will be involved in cross-disciplinary collaborations and have training opportunities to further develop and grow your scientific interests.
• Opportunity to work in close contact with other basic- and clinical-research groups at the Department of Biomedicine and experts in the field of tuberculosis
• Support from highly competent, experienced team members and potential to lead projects with a high degree of academic freedom

Key References

Ortmayr, K., de la Cruz Moreno, R. & Zampieri, M. Expanding the search for small-molecule antibacterials by multidimensional profiling. Nat Chem Biol 18, 584–595 (2022)

Anglada-Girotto, M., Handschin, G., Ortmayr, K. et al. Combining CRISPRi and metabolomics for functional annotation of compound libraries. Nat Chem Biol 18, 482–491 (2022).

Zampieri M., et al. High-throughput metabolomic analysis predicts mode of action of uncharacterized antimicrobial compounds. Science Translational Medicine Vol 10, Issue 429 (2018)

Øyås O., Borrell S., Trauner A., et al. Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis. PNAS 117 (2020)

Campos A. and Zampieri M. Metabolomics-Driven Exploration of the Chemical Drug Space to Predict Combination Antimicrobial Therapies. Molecular Cell 74, 1291-1303 (2020)

Application / Contact

In line with our and Uni Basel values (https://www.unibas.ch/en/Research/Values-Ethics/Diversity.html), we are committed to sustain and promote an inclusive culture, ensure equal opportunities and value diversity and respect in our working and learning environment.

Please address your application to Mattia Zampieri, by submitting the following requested documents: A) a cover letter, in which you also indicate for which project you wish to apply, B) a complete curriculum vitae C) the PhD application form (https://imsb.ethz.ch/research/zampieri-group.html) D) names and email addresses of at least two referees.

University of Basel

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