Team

Present Position

Career History - Academia

Career History - Industry (2005 - 2010)

Education

"I pursued Bachelor and Master in Chemistry at the Federal University of Uberlândia (Brazil), where I  started my scientific career. During my graduation, I became part of the Research Center on Natural Products, where I worked on metabolic compounds isolation from medicinal herbs using chromatography and spectroscopic techniques. From this work I wrote my monograph, and I started to be interested in studies of diseases treatment. Following my interests, I developed my research in the Laboratory of Crystallography and Computational Chemistry, investigating antigen-antibody complexes of proteins involved in Zika and Dengue diseases using molecular docking and semiempirical methods. Currently, my research interest is in membrane transporters, in particular, human dopamine transporter (hDAT). During my Ph.D., I aim to develop a comprehensive model of the transporter function of hDAT using advanced simulation techniques, such as metadynamics, calculation of the potential of mean force, and enforced rotation."

Gradisch R., Schlögl K., Lazzarin E., Niello M., Maier J., Mayer F.P., Alves da Silva L., Skopec S.M.C., Blakely R.D., Sitte H.H., Mihovilovic M.D., Stockner T. Ligand coupling mechanism of the human serotonin transporter differentiates substrates from inhibitors. (2024) Nature Communications, 15 (1), 417  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Alves da Silva L., Lazzarin E., Gradisch R., Clarke A., Stockner T. Free energy profile of the substrate-induced occlusion of the human serotonin transporter. (2024) Journal of Neurochemistry   [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Originally from the UK, I hold a Master’s degree in Molecular and Cellular Biochemistry from the University of Oxford, where I conducted my Master’s project in the research group of Professor Mark Sansom. Here, I used coarse-grained molecular dynamics methods to investigate the process of peripheral membrane protein interaction with the plasma membrane. Next, I moved to Vienna in 2019 to begin a research project in the group of Professor Bojan Zagrovic, where I explored the structure and dynamics of disordered RNA and protein molecules. Finally, in 2020 I began my PhD in this group, where I use both all-atom and coarse-grained molecular dynamics simulations to understand the regulation of an ion channel by its lipid environment. After being awarded my PhD in January 2024, my current focus is using accelerated sampling methods to dissect elements of transmembrane protein ion conductance.

Clarke A., Farr C.V., El-Kasaby A., Szöllősi D., Freissmuth M., Sucic S., Stockner T. Probing binding and occlusion of substrate in the human creatine transporter-1 by computation and mutagenesis. (2024) Protein Science, 33 (1), e4842  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Alves da Silva L., Lazzarin E., Gradisch R., Clarke A., Stockner T. Free energy profile of the substrate-induced occlusion of the human serotonin transporter. (2024) Journal of Neurochemistry   [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Erkan-Candag H., Clarke A., Tiapko O., Gsell M.A.F., Stockner T., Groschner K. Diacylglycerols interact with the L2 lipidation site in TRPC3 to induce a sensitized channel state. (2022) EMBO Reports, 23 (7), e54276; DOI: 10.15252/embr.202154276  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Clarke A., Groschner K., Stockner T. Exploring TRPC3 Interaction with Cholesterol through Coarse-Grained Molecular Dynamics Simulations. (2022) Biomolecules, 12 (7), art. no. 890; DOI: 10.3390/biom12070890  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

"I graduated with a master’s degree in Chemistry and Pharmaceutical Techniques from the University of Padua, Italy. I completed my master’s thesis with the Swiss-European mobility program at the University of Geneva, Switzerland. I had the opportunity to work on the discovery of novel small molecule-based treatments for Alport syndrome, a rare disease that inevitably leads to kidney failure. We designed a small library of possible antagonists for serotonin receptor; from the computational analysis, we then selected the two most promising molecules to chemically synthesize. I quickly became very interested in computational techniques because of their dynamical and interdisciplinary role at the interface between the molecular and biological worlds. In order to gain further experience in molecular modeling, I attended a six-month graduate research fellowship in a biotech company, in collaboration with the University of Padua. The project focused on the computational study of voltage-gated potassium channels involved in epilepsy. The presence of underlying common patterns between different receptor systems triggered my interest in computational structural biology and inspired me to join NeuroTrans program in the study of neurotransmitter transporters for central nervous system disorders."

Erika Lazzarin E., Gradisch R., Skopec S.M.C., Alves da Silva L., Szöllősi D., Maier J., Sucic S., Kanner B.I., Sitte H.H., Stockner T. Interaction of GAT1 with sodium ions: from efficient recruitment to stabilisation of substrate and conformation (2024) eLife:preprint  [Journal] [EuroPMC] [DOI] [PDF]

Gradisch R., Schlögl K., Lazzarin E., Niello M., Maier J., Mayer F.P., Alves da Silva L., Skopec S.M.C., Blakely R.D., Sitte H.H., Mihovilovic M.D., Stockner T. Ligand coupling mechanism of the human serotonin transporter differentiates substrates from inhibitors. (2024) Nature Communications, 15 (1), 417  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Alves da Silva L., Lazzarin E., Gradisch R., Clarke A., Stockner T. Free energy profile of the substrate-induced occlusion of the human serotonin transporter. (2024) Journal of Neurochemistry   [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Gradisch R., Szollosi D., Niello M., Lazzarin E., Sitte H.H., Stockner T. Occlusion of the human serotonin transporter is mediated by serotonin-induced conformational changes in the bundle domain. (2022) Journal of Biological Chemistry, 298 (3), 101613; DOI: 10.1016/j.jbc.2022.101613  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Khanppnavar B., Maier J., Herborg F., Gradisch R., Lazzarin E., Luethi D., Yang J.-W., Qi C., Holy M., Jäntsch K., Kudlacek O., Schicker K., Werge T., Gether U., Stockner T., Korkhov V.M., Sitte H.H. Structural basis of organic cation transporter-3 inhibition. (2022) Nature Communications, 13 (1), 6714; DOI: 10.1038/s41467-022-34284-8  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Bhatt M., Gauthier-Manuel L., Lazzarin E., Zerlotti R., Ziegler C., Bazzone A., Stockner T., Bossi E. A comparative review on the well-studied GAT1 and the understudied BGT-1 in the brain. (2023) Frontiers in Physiology, 14, art. no. 1145973; DOI: 10.3389/fphys.2023.1145973  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Ozvoldik K., Stockner T., Krieger E. YASARA Model-Interactive Molecular Modeling from Two Dimensions to Virtual Realities. (2023) Journal of Chemical Information and Modeling, 63 (20), pp. 6177 - 6182   [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Ozvoldik K., Stockner T., Rammner B., Krieger E. Assembly of Biomolecular Gigastructures and Visualization with the Vulkan Graphics API. (2021) Journal of Chemical Information and Modeling, 61 (10), pp. 5293 - 5303; DOI: 10.1021/acs.jcim.1c00743
scopus

Ralph completed his diploma studies in Pharmaceutical Sciences at the University of Vienna and subsequently enrolled in the international PhD Program Molecular Drug Targets at the Medical University of Vienna in 2019 and worked in the interdisciplinary lab of Prof. Thomas Stockner and Prof. Harald Sitte. During his PhD studies, Ralph combined biophysical computational approaches such as Molecular Dynamics Simulations, Docking, and protein modelling with radiotracer assays and electrophysiological measurements. He aimed to understand the dynamic behaviour of transmembrane transporters, particularly monoamine transporters. After completing his PhD, Ralph joined the Patriarchi Lab in January 2024. Here, he leverages his experience in protein dynamics and molecular pharmacology to engineer novel genetically-encoded sensors to broaden the available toolbox of fluorescent indicators. Besides the bench work, he enjoys exploring nature, hiking with his dog, and exploring the coffee business.

Gradisch R., Schlögl K., Lazzarin E., Niello M., Maier J., Mayer F.P., Alves da Silva L., Skopec S.M.C., Blakely R.D., Sitte H.H., Mihovilovic M.D., Stockner T. Ligand coupling mechanism of the human serotonin transporter differentiates substrates from inhibitors. (2024) Nature Communications, 15 (1), 417  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Alves da Silva L., Lazzarin E., Gradisch R., Clarke A., Stockner T. Free energy profile of the substrate-induced occlusion of the human serotonin transporter. (2024) Journal of Neurochemistry   [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Niello M., Sideromenos S., Gradisch R., O'Shea R., Schwazer J., Maier J., Kastner N., Sandtner W., Jäntsch K., Lupica C.R., Hoffman A.F., Lubec G., Loland C.J., Stockner T., Pollak D.D., Baumann M.H., Sitte H.H. Persistent binding at dopamine transporters determines sustained psychostimulant effects. (2023) Proceedings of the National Academy of Sciences of the United States of America, 120 (6), art. no. e2114204120; DOI: 10.1073/pnas.2114204120  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Gradisch R., Szollosi D., Niello M., Lazzarin E., Sitte H.H., Stockner T. Occlusion of the human serotonin transporter is mediated by serotonin-induced conformational changes in the bundle domain. (2022) Journal of Biological Chemistry, 298 (3), 101613; DOI: 10.1016/j.jbc.2022.101613  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Khanppnavar B., Maier J., Herborg F., Gradisch R., Lazzarin E., Luethi D., Yang J.-W., Qi C., Holy M., Jäntsch K., Kudlacek O., Schicker K., Werge T., Gether U., Stockner T., Korkhov V.M., Sitte H.H. Structural basis of organic cation transporter-3 inhibition. (2022) Nature Communications, 13 (1), 6714; DOI: 10.1038/s41467-022-34284-8  [Journal] [scopus] [PubMed] [EuroPMC] [DOI] [PDF]

Niello M., Gradisch R., Loland C.J., Stockner T., Sitte H.H. Allosteric Modulation of Neurotransmitter Transporters as a Therapeutic Strategy. (2020) Trends in Pharmacological Sciences, 41 (7), pp. 446 - 463; DOI: 10.1016/j.tips.2020.04.006
scopus

Stockner T., Gradisch R., Schmitt L. The role of the degenerate nucleotide binding site in type I ABC exporters. (2020) FEBS Letters, 594 (23), pp. 3815 - 3838; DOI: 10.1002/1873-3468.13997
scopus