Research in the Zamboni lab

Decades of research on metabolism, and more recently genome-based reconstructions, have produced detailed metabolic maps, which - for many organisms - include several hundreds of different intermediates and connecting enzymatic reactions. Despite this detailed knowledge on network topology, our capacity to predict metabolic responses to environmental stimuli or genetic perturbations is still very limited. The major burden is the lack of direct data on in vivo network operation to infer the regulatory mechanisms governing metabolic activity. To overcome this informational gap, our lab researches novel concepts and tools that monitors state and activity of metabolic networks. In particular, we strive to develop generally applicable approaches that can cope with technically difficult systems such as mammalian cells, complex environments, dynamic states, and heterogeneous populations.

We pursue a primarily data-driven approach largely based on mass spectrometry and fluorescent microscopy, which aim at collect precise information on the state and activity of metabolic networks. On all analytical platforms, we independently work on comprehensive pipelines for either high-throughput screening or very quantitative measurements for validation or targeted analyses. These data are then interpreted and integrated to infer the underlying principles and the (regulatory) mechanisms governing metabolic responses.

In parallel, we have a strong program in software development for chemometrics, automatization, workflow management, data mining, data integration, and hypothesis testing. One important goal is to maximize speed, quality, and significance of data analysis in hundreds of independent studies per year. On the other hand, this has become strictly necessary to enable large-scale, integrative numerical analysis of omics datasets such as generated on our high-throughput analytics. Tools of general interest for a broader community are released to the public.

The variety and power of our tools is suited to tackle fundamental questions in all areas where cellular metabolism is of relevance: systems biology, metabolic engineering, drug development against pathogens or cancer, toxicology, cell differentiation, nutrition, evolution, etc.

For questions related to microbes, pathogens, and yeasts we tightly collaborate with the team of Uwe Sauer at our Institute. In contrast, our activity on mammalian systems (cancer, liver, stem cells) and plants build largely on the excellence of extramural, world-wide collaborators both in Academy and Industry.

More details are available on the subpages.

References:

• Zamboni N. ¹³C metabolic flux analysis in complex systems, Curr Opin Biotechnol. 2011
• Zamboni N, Sauer U, Novel biological insights through metabolomics and ¹³C-flux analysis, Curr Opin Microbiol 2009; 12:553
  
• Sauer U, Zamboni N, From biomarkers to integrated network responses, Nat Biotechnol 2008; 26:1090
  
• Sauer U, Heinemann M, Zamboni N, Getting close to the whole picture, Science 2007; 316:550