ESR5: Simone Mariani
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Host Organization
Rossetti Lab Computational Biomedicine Forschungszentrum Jülich Supervisor Prof. Giulia Rosetti 
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Allosteric drugs development for receptor mosaics Understanding how receptors respond to stimuli in the brain is a tremendous challenge with relevant implications for human health. Over the last few years, receptors have been shown to function as both monomers and heteromers, i.e., macromolecular complexes composed of at least two different functional receptor units, displaying biochemical properties that are demonstrably different from those of their components. These are the so-called “receptor mosaics” (RM).
The cooperative interactions established in the RMs due to both exogenous ligand binding and allosteric mechanisms at the receptor/receptor interface alter the pharmacology response of the single receptor. For instance, RMs have the potential to markedly expand the diversity and specificity of G protein-coupled receptors (GPCR) signaling, particularly in neural cells, where a few key receptors have been implicated in many neurological and psychiatric disorders, including addiction. Thus, the pharmacology of the binding pockets of the different receptors building up the RM can be substantially distinct with respect to their pharmacology in the respective monomer. Moreover, the therapeutic targeting of receptor-receptor functional interactions and/or RMs in a tissue-specific or temporal manner (for example, a sub-population of receptors in a “pathological state”) might reduce detrimental side effects that may otherwise impair vital brain functions. This project aims at understanding RMs signaling mechanism at the molecular level and developing new multi-target ligands targeting pharmacologically relevant RMs. |
Brief Scientific Bio
I got my Bachelor’s Degree in Chemistry at Sapienza University of Rome (Italy). During this period, I developed a great combination of knowledge in Organic, Physical, and Computational chemistry. Then, I decided to pursue my Master's Degree in Chemistry at the University of Siena (Italy). During the last year of the program, I followed an Advanced Organic Chemistry course, focused on the theoretical and computational modeling of light photoreceptors. Immediately, I became extremely passionate about the fascinating applications of Computational chemistry. Therefore, I decided to improve my knowledge in this field by joining the Laboratory of Computational Photochemistry and Photobiology (LCCP) of prof. Massimo Olivucci. My project aimed at studying fluorescence in the optogenetic tool Archeorhodopsin-7 and designing a set of its variants. To conduct my studies I had to learn the methodologies routinely used in QM/MM studies of electronically excited states. In 2022 I joined the group of prof. Rossetti at Forschungszentrum Jülich (Germany), as an ESR in the ALLODD project.
I got my Bachelor’s Degree in Chemistry at Sapienza University of Rome (Italy). During this period, I developed a great combination of knowledge in Organic, Physical, and Computational chemistry. Then, I decided to pursue my Master's Degree in Chemistry at the University of Siena (Italy). During the last year of the program, I followed an Advanced Organic Chemistry course, focused on the theoretical and computational modeling of light photoreceptors. Immediately, I became extremely passionate about the fascinating applications of Computational chemistry. Therefore, I decided to improve my knowledge in this field by joining the Laboratory of Computational Photochemistry and Photobiology (LCCP) of prof. Massimo Olivucci. My project aimed at studying fluorescence in the optogenetic tool Archeorhodopsin-7 and designing a set of its variants. To conduct my studies I had to learn the methodologies routinely used in QM/MM studies of electronically excited states. In 2022 I joined the group of prof. Rossetti at Forschungszentrum Jülich (Germany), as an ESR in the ALLODD project.
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This project has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 956314.
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