Three projects within the interdisciplinary network National Center of Competence in Research (NCCR) TransCure contributed by our group are now published in CHIMIA, archived in Vol. 76 No. 12 (2022): NCCR TransCure - Excellence in Membrane Transport Research 2010-2022!
NCCR TransCure, funded by the Swiss National Science Foundation and the University of Bern, was active from 2010 to 2022. It provided a unique research and educational framework in the membrane transporter and ion channel field. Thanks to an interdisciplinary approach comprising physiology, structural biology, and chemistry, in parallel to a rich offering in complementary areas such as education and technology transfer, the network achieved outstanding scientific results and contributed to the education of young scientists. This issue presents the main features and milestones of the NCCR TransCure.
- 1. Molecular Similarity for Drug Discovery, Target Prediction and Chemical Space Visualization
Check it out: https://chimia.ch/chimia/article/view/2022_1045
Similar drug molecules often have similar properties and activities. Therefore, quantifying molecular similarity is central to drug discovery and optimization. Here I review computational methods using molecular similarity measures developed in my group within the interdisciplinary network NCCR TransCure investigating the physiology, structural biology and pharmacology of ion channels and membrane transporters. We designed a 3D molecular shape and pharmacophore comparison algorithm to optimize weak and unselective inhibitors by scaffold hopping and discovered potent and selective inhibitors of the ion channels TRPV6 and TRPM4, of endocannabinoid membrane transport, and of the divalent metal transporters DMT1 and ZIP8. We predicted off-target effects by combining molecular similarity searches from different molecular fingerprints against target annotated compounds from the ChEMBL database. Finally, we created interactive chemical space maps reflecting molecular similarities to facilitate the selection of screening compounds and the analysis of screening results. These different tools are available online at https://gdb.unibe.ch/tools/.
Author(s): Jean-Louis Reymond
- 2. Physiological and Molecular Function of the Sodium/Hydrogen Exchanger NHA2 (SLC9B2)
Check it out: https://chimia.ch/chimia/article/view/2022_1019
NHA2, also known as SLC9B2, is an orphan intracellular Na+/H+ exchanger (NHE) that has been associated with arterial hypertension and diabetes mellitus in humans. The objective of this NCCR TransCure project was to define the physiological and molecular function of NHA2, to develop a high resolution kinetic transport assay for NHA2 and to identify specific and potent compounds targeting NHA2. In this review, we summarize the results of this highly interdisciplinary and interfaculty effort, led by the groups of Proffs. Jean-Louis Reymond, Christoph von Ballmoos and Daniel Fuster.
Author(s): Tin Manh Ho, Stephan Berger, Philipp Müller, Céline Simonin, Jean-Louis Reymond, Christoph von Ballmoos and Daniel G. Fuster
- 3. Vitaport: A Learning and Artistic Path for Public Outreach on Transporter Biology, Health and Drug Discovery
Check it out: https://chimia.ch/chimia/article/view/2022_1063
In occasion of its conclusion, the National Center of Competence in Research (NCCR) TransCure launched a temporary learning and artistic path in the city of Bern named 'Vitaport - Was unser Körper transportiert'. The path explained how nutrients are transported through our body and how molecules find their way to the right organ to achieve their effect there. NCCR TransCure researchers, together with students of the Bern School of Design, developed ceramic objects, texts and information graphics that took the public on a multidisciplinary journey of discovery through the human body. In this article, we report about aims, development, challenges and outcome of this ambitious science outreach project in which we could experience a rewarding and successful collaboration between scientists and artists.
Author(s): Valentina Rossetti and Jean-Louis Reymond