Job ID: 98688

Cellular entry of homeoprotein-derived cell-penetrating peptides

Position: Post-doctoral Position

Deadline: 16 December 2022

Employment Start Date: 2 January 2023

Contract Length: 1 year

City: Paris

Country: France

Institution: Collège de France

Department: Center for Interdisciplinary Research in Biology

Description:

Cell penetrating peptides (CPPs), which exhibit the remarkable ability to cross cell membranes, can be bound to bioactive cargos and thus are of great interest for biomedical and biotechnological applications. However, their mode of entry into cells remains to be elucidated. Sagan’s group has demonstrated the importance of key cellular parameters for CPP entry (Acc. Chem. Res. 2017, 50, 12, 2968–2975) ; Sagan and Venance’s groups in a collaborative study show that CPP entry evoked ionic fluxes whose magnitude depends on CPP concentration, on glycosaminoglycans at the cell surface and membrane potential (ms under preparation), using single-cell double patch-clamp recordings on cell cultures.

Collaborative project between

1) Center for Interdisciplinary Research in Biology (CIRB, Inserm/CNRS)-Team: Dynamic and Pathophysiology of Neuronal Networks, Collège de France, Paris

2) LBM- Laboratory of Biomolecules, Sorbonne University, Paris

We are recruiting a highly-motivated post-doctoral student who will push forward at a physiological level the aforementioned observations using electrophysiology (patch-clamp) and two-photon imaging. The “Physiological level” includes the impact on ionic fluxes of homeoproteins in acute brain slices in different conditions involving different perineuronal net composition in various neuronal and glial populations.

Developments to be carried out during the year (possibly extended):

  1. i) analysis with homeoproteins selected for their interaction with specific sugar subtypes at the cell surface.
  2. ii) To transpose the conditions of electrophysiological measurements set up to mouse brain slices which will allow to qualify physiologically the results obtained in cell culture.

iii) To combine patch-clamp to two-photon imaging which will allow to observe concomitantly the translocation of CPPs and homeoproteins to the membrane permeabilization and the evoked-currents.

  1. iv) To analyze the effect of the controlled modulation of surface sugars on the membrane disruption and translocation of CPPs and homeoproteins.

The expected results will undoubtedly bring an essential contribution to the understanding of the fundamental mechanisms of translocation of CPPs and homeoproteins for upcoming biomedical and biotechnological applications.

Candidates should hold a Ph.D. and have solid experience with patch-clamp recordings & analysis (certified by publications and PhD diploma).

All necessary instruments and experimental approaches (electrophysiology, two-photon imaging, optogenetics) will be rendered available to the engineer fellow to ensure project feasibility and success.

The position is financed for 1-year by ANR grant (with a possible one-year extension).