PhD position quantitative biology: metabolism in mediating functions of tumor suppressor/oncogenes

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-ot-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 investigate the role of metabolism in mediating functions of tumor suppressor and oncogenes (60% wet lab and 40% computational).

Adapting existing and developing improved experimental protocols for the high-throughput metabolomics analysis of CRISPR engineered cell lines.

• Mapping the metabolic adaptome of cancer cell lines to genetic perturbations of tumor suppressor and oncogenes
• Determining the underlying mechanisms that link modulation of gene expression to metabolic phenotypes
• Developing network-based approaches to investigate and predict response to genetic perturbation in an in vivo context
• Support and preparation of scientific reports and journal articles

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 cell cultures (cell lines) in the laboratory
• 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
• Experience with and/or motivation to learn programming language (e.g. Matlab, R or Python)
• Good communication skills

Any of the following will be a plus:

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

• You will have access to state-of-the-art research equipment in metabolomics, cell biology, time-Japse microscopy.
• You will work in a dynamic and highly interdisciplinary team including computer scientists and 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 in Basel
• Support from highly competent, experienced team members and potential to lead projects with a high degree of academic freedom

Key References
Ortmayr, K. and Zampieri M. "Sorting-free metabolic profiling uncovers the vulnerability of fatty acid ß-oxidation in in vitro quiescence models". To appear in Molecular Systems Biology 2022

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

Ortmayr, K., Dubuis, S. & Zampieri, M. Metabolie profiling of cancer cells reveals genome-wide crosstalk between transcriptional regulators and metabolism. Nat Commun 10, 1841 (2019).

Dubuis, S., Ortmayr, K. & Zampieri, M. A framework for large-scale metabolome drug profiling links coenzyme A metabolism to the toxicity of anti-cancer drug dichloroacetate. Commun Bio! 1, 101 (2018).

Application / Contact

In line with our and Uni Basel values (https://www.unibas.ch/en/Research/Values-Ethics.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.