Research Unit on BioActive Molecules
WHO WE ARE
The team is composed of 4 principal investigators: Gemma Fabriás, Josefina Casas, José Luis Abad, and Antonio Delgado and complemented with a variable number of postdoctoral researchers, PhD students, master, and grade students as well as lab technicians.
The team has all the capabilities and access to all sort of scientific and technical instrumentation and facilities at University of Barcelona (CCiT-UB: http://www.ccit.ub.edu/EN/home.html) and IQAC-CSIC https://www.iqac.csic.es/facilities/
IQAC-CSIC, Department of Biological Chemistry
University of Barcelona
C/ Jordi Girona 18-26
Research Unit on BioActive Molecules
RUBAM is a multidisciplinary team who focuses their research on biologically active organic compounds (lipids, glycolipids, enzyme inhibitors) at the interface between chemistry and biology. With a specific interest on the chemistry and biology of lipids (phospholipids, sphingolipids (SLs) and glycolipids), the team focuses special efforts in the development of chemical probes and biochemical tools and the discovery of new molecules for the treatment of diseases related to sphingolipids and their implications in diseases as Niemann- Pick, Gaucher and Farber disease.
WHAT WE DO
With long expertise in the design, synthesis and biological testing of small organic molecules, the group has developed and improved their capacities and services related to lipidomics, enzymology and cell and molecular biology. The services they offer are:
- Lipidomics: Hyphenated mass spectrometry techniques (GC-MS and LC-MS). Comprehensive analysis of cellular lipids that encompass fatty acyls, glycerolipids, glycerophospholipids and sphingolipids. The services include sample preparation, lipid identification by mass spectrometry, LC-MS lipid profiling, and LC-MS lipid quantification.
- Stereoselective synthesis of chemically modified sphingolipids. Click chemistry.
- Chemical probes: The group has developed several chemical probes and biochemical tools to monitor the enzyme activity. Some of their probes are available upon request. See: https://www.rubam.net/chemical-probes/
- Cellular and molecular biology techniques.
WHOM WE WORK FOR
- Health and Life Sciences
- INSERM U.858
Their current research lines are based on the biomedicine of sphingolipids and their implication in the progression of rare diseases and high social and economic impact diseases:
- Pharmacological chaperones in mutated enzymes for rare diseases associated to sphingolipid metabolism. Biological models include Niemann-Pick, Gaucher and Farber disease.
- Design, synthesis, and application of chemically modified sphingolipids as tools for cell biology studies.
- Design and synthesis of probes for the development of High Throughput Screening (HTS) methods for enzymes of the SLs metabolism.
- Development of chemical tools and methods to determine lipid compositions and changes in sphingolipid profiles.
- New Proteolysis TArgeting ChimeraS (PROTACS) for the induced protein degradation of key SLs enzymes.
- Chemical probes for the study of the metabolism and function of sphingolipids: design, synthesis, validation, and applications PI: Prof. Gemma Fabriàs (RUBAM). 2018-2020. Ministerio de Economía y Competitividad. Participating Organizations: CSIC and University of Barcelona.
- Transautophagy: European Network of Multidisciplinary Research and Translation of Autophagy knowledge PI: Dr. Caty Casas (Universitat Autònoma de Barcelona). 2016-2020. EU, COST Action.
- MitoCholERaxis: new tools against obesity related diseases. PI: Jose Carlos Fernández-Checa Torres, (IIBB-CSIC). BBVA Programe.2018-2019. Participating Organizations: IIBB & RUBAM.
- Consolidated Research Group from Generalitat de Catalunya. PI: Gemma Fabriàs (RUBAM). 2017-2019. Generalitat de Catalunya.
GENERATION OF CHEMICAL PROBES
In order to monitor the activity of enzymes of the sphingolipids metabolism, the research group has developed several chemical probes and biochemical tools:
Azide-Tagged Sphingolipids for cellular trafficking studies:
- HPA-12 CerT inhibitor
Fluorogenic substrates to determine enzyme activity:
- RBM148 Sphingosine-1-phosphate lyase (SPL) activity
- RBM14-12, RBM14C24:1 selective for NC
- RBM15C18:1 selective for ACER1 and ACER2, with very low NC activity
- Mira E, et al. SOD3 improves the tumor response to chemotherapy by stabilizing endothelial HIF-2α, Nat Commun. 2018 Feb 8;9(1):575. doi: 10.1038/s41467-018-03079-1.
- Sanllehí, P. et al. The First Fluorogenic Sensor for Sphingosine-1-Phosphate Lyase Activity in Intact Cells. Commun. 2017, 53 (39), 5441–5444.
- Gómez-Grau, M. et al. New Murine Niemann-Pick Type C Models Bearing a Pseudoexon-Generating Mutation Recapitulate the Main Neurobehavioural and Molecular Features of the Disease. Rep. 2017, 7 (1), 41931.
- Serra-Vinardell, J. et al, Selective Chaperone Effect of Aminocyclitol Derivatives on G202R and Other Mutant Glucocerebrosidases Causing Gaucher Disease. J. Biochem. Cell Biol. 2014, 54, 245–254.
- Serra-Vinardell, J. et al. Glucocerebrosidase Enhancers for Selected Gaucher Disease Genotypes by Modification of α-1-C-Substituted Imino-D-Xylitols (DIXs) by Click Chemistr ChemMedChem 2014, 9, 1744–1754.
Other relevant publications: http://www.rubam.net/publications/