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Using metabolic fingerprints to rationally design combination therapies

Event Details:

  • Date: - -
  • Venue: Collegio A Volta, Pavia
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On the 28th of November 2019 Mattia Zampieri, ETH Zurich, will give a seminar entitled Using metabolic fingerprints to rationally design combination therapies at 2.00 pm in the College lecture theatre (Collegio A Volta).  All students are invited to attend, especially those reading Medicine, Biology, Biotechnology and Pharmaceutical Sciences. The poster of the lecture can be downloaded here.

Abstract
Despite rapid technological progress, the discovery of novel antibiotics has been stalled for the past 50 years. To combat the growing burden of antibiotic resistance, innovative drug discovery paradigms are required to improve and expedite the antibiotic discovery process. A crucial bottleneck in drug discovery is the identification of compounds’ Mode of Action (MoA). To address this problem we developed a rapid and systematic metabolome profiling strategy to classify the MoA of bioactive compounds. In contrast to existing methods based on phenotypic drug profiling, mostly on the basis of growth assays, we exploit here the intracellular response of about 1000 metabolites as a truly multiparametric readout of the cellular response. The specific advance over existing metabolic platforms is a faster throughput of 1-2 orders of magnitude, allowing our combined MS-based metabolomics and computational workflow to scale with the size of typical compound libraries. I will illustrate how this technology enables monitoring the metabolic response of Escherichia coli to 1279 human targeted drugs and revealed an unexpectedly large spectrum of metabolic effects in E. coli. Combining metabolic profiling with chemogenomic data, we predicted drug MoAs and epistatic drug interactions. Our approach opens new opportunity in systems pharmacology and reveals new ways to expand the search for new antimicrobial treatments to compounds with no growth-inhibitory activity.

Keywords: Metabolomics, Antibiotics, Drug Mode of Action

References
Campos A, Zampieri M*. Metabolomics-driven exploration of the chemical drug space to predict synergistic antimicrobial effects. Molecular Cell 2019.

Biography
Mattia Zampieri is a junior PI at the Institute of Molecular Systems Biology of ETH in Zurich. He studied Bioengineering in Padova before doing a PhD in Bioinformatics at the International School for Advanced Studies in Trieste and Boston University. During his PhD he worked on mathematical modeling of microbial metabolism and reverse engineering transcriptional regulatory network from molecular profiling data. In 2011 he moved to the lab of Prof. Uwe Sauer at ETH where he developed novel high throughput metabolomics frameworks and quantitative models to study the role of microbial metabolism in mediating the response to antimicrobial treatments. His research led to unique high-throughput metabolomics frameworks and computational tools broadly applicable to diverse biological systems and therapeutic areas, opening new opportunities in systems biology and systems pharmacology

Image
Bioblasts (Odra Noel, Wellcome Collection)

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