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Molecular Cell Biophysics

Juniorprof. Dr. rer. nat. Katia Cosentino

Juniorprof. Dr. rer. nat. Katia Cosentino

Contact details

The Cosentino group aims to understand the molecular mechanisms of membrane pore formation by pore forming proteins (PFPs), a big class of proteins with crucial functions in infection, immunity, cancer and neurodegeneration. Specifically, we focus on PFPs involved in apoptosis and pyroptosis, two therapeutically relevant regulated cell death processes. To dissect the spatio-temporal assembly of membrane pores we apply several biophysical approaches, including quantitative single molecule imaging.

Research topics

  • Spatio-temporal assembly of Gasdermins pores in pyroptosis
  • Modulation of Gasdermin pore formation by the membrane environment
  • Crosstalk between apoptosis and pyroptosis
  • Modulation of cell death outcome

Model systems

  • Protein reconstitution in artificial membrane systems (i.e. liposomes, supported lipid bilayers, nanodiscs)
  • Mammalian cells endogenously or transiently expressing PFPs
  • Isolated organelles and supported plasma membranes

Methods

  • Expression and purification of fluorescently-labeled PFPs
  • Activity and permeability assays of PFPs and cofactors
  • Chemical or optogenetic activation of regulated cell death
  • Single molecule fluorescence imaging and super resolution microscopy
  • Stoichiometric analysis of protein complexes
  • Atomic force microscopy and spectroscopy

Selected publications

Cosentino K, Hertlein V, Jenner A, Dellmann T, Gojkovic M, Peña-Blanco A, Dadsena S, Wajngarten N, Danial JSH, Thevathasan JV, Mund M, Ries J, & Garcia-Saez AJ (2022) The interplay between BAX and BAK tunes apoptotic pore growth to control mitochondrial-DNA-mediated inflammation. Molecular Cell, in press. doi: 10.1016/j.molcel.2022.01.008 pdf

Danial JSH, Quintana Y, Ros U, Shalaby R, Margheritis EG, Chumpen Ramirez S, Ungermann C, Garcia-Saez AJ, & Cosentino K (2022) Systematic assessment of the accuracy of subunit counting in biomolecular complexes using automated single-molecule brightness analysis. The Journal of Physical Chemistry Letters 13(3):822-829 doi: 10.1021/acs.jpclett.1c03835 pdf

Jenner A, Shalaby R, & Cosentino K (2020) Quantitative single-molecule imaging of protein assembly in membranes. Advances in Biomembranes and Lipid Self-Assembly, eds Iglič A, Rappolt M, & García-SÁez AJ (Academic Press), Vol 31, pp 81-128. doi: 10.1016/bs.abl.2020.02.004. pdf