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Pau Gorostiza Langa

Group Leader / ICREA Research Professor
+34 934 020 208
pgorostizaibecbarcelona.eu
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Nanoprobes and Nanoswitches

Pau Gorostiza Langa

About

Research in the laboratory focuses on developing nanoscale tools to study biological systems. These tools include instrumentation based on proximity probes, such as electrochemical tunnelling microscopy and spectroscopy and single molecule force spectroscopy, that we apply to investigate electron transfer in individual redox proteins, and other biophysical and biochemical interactions.

These studies are relevant to understand lipid membrane dynamics, to the development of biosensors and molecular electronics devices, and have led to the discovery of long-distance electrochemically gated electron transport between partner proteins of the respiratory and photosynthetic chains.

Another set of nanotools that we are developing is based on engineered molecular actuators that can be switched with light, such as azobenzene, which can be chemically attached to biomolecules in order to remotely control their activity (photopharmacology). They include peptide inhibitors of protein-protein interactions, small molecule enzymatic inhibitors, and photoswitchable ligands of a diversity of other proteins.

Among several applications, these compounds have enabled photoactivated chemotherapy, photocontrol of cellular signaling mediated by ion channels and G protein-coupled receptors, photocontrol of cardiac activity and locomotion, sensory restoration, and photocontrol of brain waves.

Based on these tools, we have also developed two-photon pharmacology to manipulate and study the activity of neurons and glia in intact brain tissue with pharmacological selectivity and sub-cellular three-dimensional resolution.

Rational structural modifications of the chemotherapy agent methotrexate enabled control of cytotoxic efficacy with light. In vitro and in vivo experiments showed that the new compound, named phototrexate, behaves as a potent antifolate in its photoactivated configuration, and that it is nearly inactive in its thermodynamically stable state. The insights provided by this work open up new possibilities for developing innovative agents for light-controlled precision chemotherapy. (Matera et al., 2018). Image credit: Carlo Matera & Grafino.it.
Electrochemical tunneling spectroscopy and molecular dynamics simulations indicate that a reduced ionic density at the volume confined between redox protein partners hCc (left, orange) and pCc1 (right, green) causes an extended electric field (equipotential lines shown in the background) that allows long distance charge transport between them. Heme groups are highlighted in each protein (Lagunas et al., 2018). Image credit: Alba Nin-Hill.

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