Tobias Walther PhD

Associate Professor of Cell Biology

Research Interests

Organelle homeostasis; Plasma membrane organization; Lipid metabolism, Lipid Droplets; Eisosomes; Sphingolipid metabolism; Systematic genetics; RNAi screening; Mass-spectrometry based proteomics

Current Projects

-mechanism and function of plasma membrane organization
-regulation and homeostasis of plasma membrane composition
-cell biology of fat storage

Research Summary

We combine cell biology, biochemistry, structural biology and physiology approaches to study cellular compartmentalization and its consequences. In particular we focus on

  1. Mechanisms of plasma membrane organization
  2. The biology of cellular energy storage.

Extensive Research Description

Cellular energy is stored as fat in cytoplasmic “lipid droplets”. These universal organelles are present in most cells, but are still poorly characterized. They pose many unresolved questions: How are lipid droplets formed? How is fat stored there? How is it mobilized again? How are proteins and the reactions they mediate specifically targeted there? Lipid droplets are the cellular hallmark of many common diseases, including obesity, diabetes and atherosclerosis. Answers to these exciting basic questions are therefore also important for human physiology and pathology. Similarly, compartmentalization of reactions is a fundamental for cell biology, but has many implications for human health. In eukaryotic cells, it is primarily achieved in organelles. In addition, membranes are often highly organized spatially to mediate the compartmentalization of reactions. One membrane with especially pronounced lateral organization is the cell delimiting plasma membrane. Our efforts center on understanding the mechanistic principles involved in membrane organization and its physiological functions. For example, we investigate how signaling specificity at the plasma membrane is achieved. Furthermore, we aim to understand how structure and composition of the plasma membrane are homeostatically maintained.


Selected Publications

  • Krahmer N, Guo Y, Wilfling F, Hilger M, Lingrell S, Heger K, Newman HW, Schmidt-Supprian M, Vance DE, Mann M, Farese RV Jr, Walther TC. Phosphatidylcholine Synthesis for Lipid Droplet Expansion Is Mediated by Localized Activation of CTP:Phosphocholine Cytidylyltransferase. Cell Metab.2011 Oct 5;14(4):504-15.
  • Farese, R.V. † and Walther, T.C†. Lipid Droplets finally get a little R-E-S-P-E-C-T. Cell (2009), 139: 855-860.
  • Berchtold, D., and Walther, T.C. †: TORC2 plasma membrane localization is essential for cell viability and restricted to a distinct domain, Mol. Biol. of the Cell, (2009), 20:1565-75.
  • Froehlich, F., Moreira, K., Aguilar, P.S., Hubner, N., Mann, M., Walter, P. and Walther, T.C. †: A genome-wide screen for genes affecting eisosomes reveals Nce102 function in sphingolipid signaling, J. Cell Bio. (2009), 185: 1227-42.
  • Guo, Y.*, Walther, T.C.* †, Rao, M., Stuurman, N., Goshima, G., Terayama, K., Wong, J.S., Vale, R.D., Walter, P. and R.V. Farese†: Functional genomic screen reveals genes involved in lipid droplet formation and utilization, Nature (2008),453, 657-661.
  • deGodoy, L., Olsen, J.V., Cox, J., Nielsen, M.L., Hubner, N.C., Froehlich, F., Walther, T.C. † and M. Mann†: Comprehensive, mass spectrometry-based proteome quantitation of haploid versus diploid yeast. Nature Sept.(2008), 455, 1251-4.
  • Walther, T.C.* †, Brickner, J.H.*, Aguilar, P.S. Bernales, S., Pantoja, C. and P. Walter.: Eisosomes mark static sites of endocytosis, Nature (2006), 493, 998-1003.

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