Humboldt-Universität zu Berlin - Experimentelle Biophysik

Camille Brouillon

G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins in the human genome, with approximately 800 members. 34% of FDA’s approved Drugs act on GPCRs (Sriram & Insel, 2018). As such, they represent a crucial target for optogenetic therapies to achieve a precise control of downstream cellular processes.

Invertebrate opsins make perfectly suited candidates for light sensitive GPCRs since as opposed to animal opsins they are bistable, therefore do not bleach over repeated stimulation and can be toggled ON and OFF with light. However, most of the current light-sensitive GPCRs are sensitive to blue or UV-light, which is highly scattered in tissue and phototoxic at high intensities. Red-sensitive GPCRs are thus crucial to achieve deep-tissue and non-invasive modulation(Tromberg et al., 2000; Wilson et al., 1988). Some shrimps and fishes naturally possess long-wave opsins which make them interesting targets for red-sensitive light sensitive GPCR tools.

My PhD project focuses on the functional study of these opsins in human cells, to determine their G-protein signaling pathways, their sensitivities to light intensity and their spectral, kinetic and bistable properties to offer new tools for GPCR optogenetic therapies.

References :

Sriram, K., & Insel, P. A. (2018). G Protein-Coupled Receptors as Targets for Approved Drugs : How Many Targets and How Many Drugs? Molecular Pharmacology, 93(4), 251‑258. https://doi.org/10.1124/mol.117.111062

Tromberg, B. J., Shah, N., Lanning, R., Cerussi, A., Espinoza, J., Pham, T., Svaasand, L., & Butler, J. (2000). Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy. Neoplasia (New York, N.Y.), 2(1‑2), 26‑40. https://doi.org/10.1038/sj.neo.7900082

Wilson, B. C., Patterson, M. S., Flock, S. T., & Moulton, J. D. (1988). The Optical Absorption and Scattering Properties of Tissues in the Visible and Near-Infrared Wavelength Range. In R. H. Douglas, J. Moan, & F. Dall’Acqua (Éds.), Light in Biology and Medicine : Volume 1 (p. 45‑52). Springer US. https://doi.org/10.1007/978-1-4613-0709-9_6