Biosketch

Prof. dr. Matthias Heinemann

Matthias Heinemann has been trained as a chemical engineer with a PhD degree in 2003, but turned into a biologist during his postdoc time. His research interest lies in the field of microbial metabolism, with key questions of his research being (i) how does core carbon and energy metabolism function, and (ii) how does primary metabolism control other cellular functions? He uses a unique combination of computational and experimental approaches to challenge concepts and dogmas/notions. Matthias has made important contributions to the fundamental understanding of metabolism: For instance, he found that cells can measure intracellular flux – the rate of metabolic activity – and use this information for regulation of other metabolic fluxes, opening up a completely new view on regulation of metabolism. Also, he found that flux-sensing can lead to bistability in metabolism, can lead to antibiotic tolerant persisters and recently showed that the metabolism of yeast is an autonomous oscillator, which orchestrates the cell cycle also in a flux-dependent manner.

Beyond, Matthias has developed a series of enabling technologies and resources for metabolomics, proteomics and cell biology. For instance, he developed a microfluidic device for microscopic monitoring of yeast cells, which allowed for the first time to observe yeast over its whole lifespan, and with a collaborator he generated the reference proteomics dataset for Escherichia coli by quantifying the levels of expressed proteins over a wide range of growth conditions. Also, his lab developed biosensors to measure glycolytic flux in single cells. His main current research areas include:

• Metabolism as a player in eukaryotic cell cycle control: identification of the nature of cell-cycle autonomous metabolic oscillations and how these oscillation control cell cycle;

• Metabolism and the biophysics of the cytoplasm: identification of how metabolic activity could control biomolecular interactions and the cytoplasm as an active matter.

Three top publications 2017-2022

1. Takhaveev V, Özsezen S, Smith EN, Zylstra A, Chaillet ML, Chen H, Papagiannakis A, Milias-Argeitis A & Heinemann M (2023) Temporal segregation of biosynthetic processes is responsible for metabolic oscillations during the budding yeast cell cycle. Nature Metabolism 5: 294–313; DOI: https://doi.org/10.1038/s42255-023-00741-x

With sophistic single-cell analyses we demonstrated that biosynthetic processes are partly temporally segregated over the course of the cell cycle. This discovery, correcting reports that have prevailed for more than 50 years, brings us closer towards unraveling the intrinsic metabolic rhythm of the eukaryotic cell.

2. Litsios A, Huberts DHEW, Terpstra H, Guerra P, Schmidt A, Buczak K, Papagiannakis A, Rovetta M, Hekelaar J, Hubmann G, Exterkate M, Milias-Argeitis A* & Heinemann M* (2019) Differential scaling between G1 protein production and cell size dynamics promotes commitment to the cell division cycle in budding yeast, Nature Cell Biology 21, 1382-1392; DOI: https://doi.org/10.1038/s41556-019-0413-3

Here, we showed that dynamics of protein production and cell size are decoupled during G1, leading to increased levels of Cln3 to trigger Start. With this work, we solved the long-standing enigma on how eukaryotic cells commit to a new round of cell division.

3. Niebel B, Leupold KES & Heinemann M (2019) An upper limit in Gibbs energy dissipation governs cellular metabolism, Nature Metabolism 1: 125-132; DOI: https://doi.org/10.1038/s42255-018-0006-7

Through analysis of experimental data with a novel thermodynamic/stoichiometric model, we showed that an upper limit in Gibbs energy dissipation rate governs metabolism. According to one of the reviewers: “This work will have ‘transformative impact on the way we understand cellular metabolism”.