Pau Gorostiza

Pau Gorostiza
Institut de Bioenginyeria de Catalunya (IBEC), Barcelona
Project leader

Light regulated drugs to restore sight.

• Eduardo Fernández
  Universidad Miguel Hernández de Elche (UMH), Elche

• Amadeu Llebaria Soldevila
  Consejo Superior de Investigaciones Científicas (CSIC), Madrid

• Jordi Manel Monés Carilla
  Barcelona Macula Foundation Research (BMF), Barcelona

• Pedro de la Villa Polo
  Universidad de Alcalá (UAH), Alcalá de Henares (Madrid)

Retinal degenerative-based blindness are due to the progressive loss of photoreceptor cells (PhRs), leading to visual impairment with very limited treatment options. The retina's layers of neurons support PhRs to acquire, process, and transmit visual information to the brain. Retinal bipolar cells respond to PhR activation through mGlu6 receptors, which are exclusively expressed in these cells. Thus, directly controlling mGlu6 receptors with light should allow mimicking the physiological signaling in the retina and restoring visual inputs to the brain. We have developed potent photoswitchable drugs of mGlu6 receptors that enable reversibly controlling receptor activity with dim white light in vitro. The best compounds allow restoring light guided behavior in a mouse model of blindness (both by intravitreal injection and by topical administration) and visual acuity in a zebrafish model of blindness (by direct application in water). The compound library has been protected by a patent. These compounds thus act as "molecular prostheses" by restoring light-dependent activation of mGlu6 receptors and retinal signaling. They constitute a potentially disruptive technology to restore vision with small molecule drugs and patient-friendly administration routes.

Pau Gorostiza is currently an ICREA Research Professor at the Institute for Bioengineering of Catalonia, where he develops photoswitchable ligands of neuronal proteins and studies charge transport in redox proteins and photosynthetic complexes using EC-STM/AFM. He graduated in physics at the University of Barcelona (UB), where he obtained his PhD in the field of semiconductor electrochemistry. He worked at the UB microscopy facility in AFM and STM of biological samples, and in nanotechnology for materials science. He has also visited the CNRS - Université Pierre et Marie Curie (France), and the University of California at Berkeley (USA). Gorostiza has published more than 120 articles and holds 9 patents (5 licensed). (Read full CV).

His research in the laboratory focuses on developing nanoscale tools to study biological systems. These tools include 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, pupillary reflex, 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.

Institut de Bioenginyeria de Catalunya (IBEC)
Parc Científic de Barcelona (PCB)
Edifici Clúster C/ Baldiri Reixac 10-12
08028 Barcelona
Tel.: (+34) 93 402 02 08

Email: [email protected]