Genomics, mechanism and function of eukaryotic membrane traffic

“The idea is to look for ways that can transform molecular interactions, biochemical activities and biophysical mechanisms into logical and informational structures and processes. This will lead to an understanding of the cell as a logical and computational machine.”            – Paul Nurse, Great Ideas of Biology, 2003.

How does cellular complexity emerge from microscopic disorder? As a physicist practicing biology, I am interested in how cells are organised and function. I study the dynamic endomembrane organelles of eukaryotic cells, and the network of vesicles that traffic cargo between them. I wish to understand how local molecular interactions generate the global membrane traffic network.

What genomic variations drive the diversity of membrane traffic across species?

How do organelles maintain their identity despite constant molecular exchange?

How do cells use membrane traffic to regulate distributed biochemical activities?

I combine eukaryotic genomics, mathematical models, and cell-biological experiments to address these issues. I use eukaryotic cellular and genomic diversity as sources of interesting new systems and questions. I develop rigorous tools to convert cell-biological hypotheses into mathematical models, in collaboration with computer scientists. I frame predictions in terms of specific molecules and phenotypes, and test these in collaboration with experimental cell biologists.

  • Chib, S., Das, S. G., Venkatesan, S., Seshasayee, A. S. N., & Thattai, M. (2018). Using stochastic cell division and death to probe minimal units of cellular replication. New J. Phys., doi.org/10.1088/1367-2630/aab197
  • Thattai, M. (2017). Organelle acidification: an ancient cellular leak detector. BMC Biol 15: 51.
  • Dey, G., Thattai, M., & Baum, B. (2016). On the archaeal origins of eukaryotes and the challenges of inferring phenotype from genotype. Trends Cell Biol 26: 476-485.
  • Mani, S., & Thattai, M. (2016). Stacking the odds for Golgi cisternal maturation. eLife, 5: e16231.
  • Purkanti, R., and Thattai, M. (2015). Ancient dynamin segments capture early stages of host-mitochondrial integration. Proc. Natl. Acad. Sci. USA, 10.1073/pnas.1407163112.
  • Ramadas R, Thattai M (2013) New organelles by gene duplication in a biophysical model of eukaryote evolution. Biophys. J. 104: 2553.

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Simons Centre for the Study of Living Machines