Light for control and analysis of nervous system - Piotr Bregestovski - 16.11.22
Piotr Bregestovski biosketch
Born in USSR - Ukraine
Lived: ≈1/3 of life in Ukraine, ≈1/3 of life in Russia , ≈1/3 - in France, ≈ 1/70-th - in Italy. Love habitants of all these, as well as other countries.
Graduated Dniepropetrovsk State University (USSR), chair of bionics.
1974 - PhD thesis in Puschino - center of biological research of the USSR.
Main topic: Analysis of functioning nicotinic ACh receptors in neuro-muscular junction. First publication: Nature 1972
1974-1977 Analysis and first physiological evidence of conformation of ACh receptor channel during activation. Nature - 1977
1978 - postdoctoral position at Biophysical department of University College London (head prof. B. Katz). Worked with prof. R. Miledi - first estimation of Ca- permeability of ACh receptor channels in neuro-muscular synapse. Nature - 1979
1983 - invited professor to Ecole Normale Superieure, Lab. of Neurobiology (head prof. P. Ascher). Discovery of Mg2+ block of NMDA receptor channels. Nature 1984.
1981- 1990 - worked in Cardiology Research Centre. Analyzed physiological role of ion channels in smooth muscle cells and human blood cells.
Nature paper in 1986 - discovery of modulation K channels in human T-lymphocytes.
1991 - moved to France, Paris.
2003 - moved to Marseille.
Now - Emeritus Directeur de recherche in INSERM, France.
Also in Russia: professor of physiology in Kazan Medical Medical University and Moscow Institute of Physics and Technology.
Collaborated/collaborate with scientists from Italy, Spain, Germany, Greece, Nederlands, USA, England, Russia, Ukraine...
Research topics/Fields of experience:
Molecular physiology and biophysics of ionic channels, electrophysiological and image analysis of synaptic transmission; fluorescent monitoring of ions and proteins; confocal imaging; modulation of synaptic function; genetically encoded probes.
Optogenetics - using of photosensitive transmembrane bacterial proteins capable to cause excitation or inhibition of cellular activity under illumination by a different wavelength.
Optosensorics - using specific genetically encoded biosensors for non-invasive analysis of intracellular, concentration of ions and other cytoplasmic components. Biosensors are macromolecular protein constructs that have fluorophore groups capable to change selectively fluorescence upon interaction with specific ions, molecular groups or proteins. Main categories of genetically encoded biosensors are: (a) consisting of a single fluorescent protein sensitive to a specific molecule or ion (single FP-sensors): (b) consisting of two fluorescent proteins and working either on the principle of ratiometric analysis or resonance energy transfer from the donor fluorescent protein to the acceptor (FRET-sensors).
Optopharmacology is based on the ability of certain molecules (azobenzenes, spiropiranes, diarylethenes) to change their conformation upon illumination with the light of a specific wavelength. Optopharmacological compounds are chemical constructs, which consist of: (i) photoswitch, capable to change conformation or charge distribution upon illumination; (ii) molecule capable specifically modulate a function of a target protein, i.e. agonists or antagonists and in some cases (iii) anchor molecule (frequently, maleimide, capable of forming covalent bonds with cysteines), for increasing photochrome specificity. Photochromic molecules represent unique tools for spatially and temporally precise control of numerous biological processes, including neuronal activity. Different types of photoswitchable regulators have been designed and characterized for a large number of ligand-gated receptors in the mammalian nervous system [1,2].
Recent achievements and future perspectives of optopharmacology in the light-induced modulation of receptor-operated channels, as well as optosensoric analysis of ionic transients at synaptic activation of brain slices from transgenic mice will be discussed.
1. Kramer, R.H., Mourot, A. and Adesnik, H., (2013). Optogenetic pharmacology for control of native neuronal signaling proteins. Nature neuroscience, 16(7), p.816-823.
2. Bregestovski, P., Maleeva, G. and Gorostiza, P., 2018. Light‐induced regulation of ligand‐gated channel activity. British journal of pharmacology, 175(11), pp.1892-1902.