OFFER DEADLINE01/03/2021 18:00 - Europe/Brussels
EU RESEARCH FRAMEWORK PROGRAMMEH2020 / Marie Skłodowska-Curie Actions COFUND
DEPARTMENTResearch Unit on Bioactive Molecules (RUBAM)
1. CONTACT PERSONS / SCIENTISTS IN CHARGE
- Bernat Crosas (firstname.lastname@example.org)
“Regulation of the proteasome” (RP)
Molecular Biology Institute of Barcelona (IBMB-CSIC)
- Antonio Delgado (email@example.com)
“Research Unit on Bioactive Molecules (RUBAM)”
Group Web: http://www.rubam.net/
Institute for Advanced Chemistry of Catalonia (IQAC-CSIC) and University of Barcelona (UB)
2. PROJECT KEYWORDS
• Ubiquitin-Proteasome system
• Protein degradation
• Molecular and cellular biology
• Organic synthesis
• Chemical biology
• In silico analysis
3. BRIEF DESCRIPTION OF THE CENTERS / RESEARCH GROUPS
The host groups are based at two different Institutes of the Spanish National Research Council (CSIC), an autonomous, multisectoral, and multidisciplinary research state agency with more than 100 Institutes throughout Spain, most of them devoted to scientific and technical research in all branches of knowledge. The “Regulation of the proteasome” (RP) group is based at the Molecular Biology Institute of Barcelona (IBMB-CSIC), located in the Barcelona Science Park (PCB) inside the “Diagonal Portal of Knowledge Campus” of the University of Barcelona (PKC), the main reference cluster in southern Europe in the field of University teaching, research and knowledge transfer. The goal of the group is to examine novel levels of regulation of the proteasome pathway focusing on the mechanisms that control proteasome function and its interaction with protein substrates.
RUBAM is a multidisciplinary group based at the Institute for Advanced Chemistry of Catalonia (IQAC), also in the UB Campus area. The group is composed of staff members of CSIC and UB and focuses its research on the design, synthesis and evaluation of chemical probes and biochemical tools to monitor and modulate sphingolipid localization and activity. In a recently started collaboration, both RP and RUBAM groups have undertaken the development of a new concept of proteolysis targeting chimeras (“protacs”) addressed at cellular targets of biomedical relevance and high therapeutic potential.
In terms of facilities and equipment the host groups fully meet the requirements necessary for the successful execution of a research project in chemical biology. In addition to the own services, access to the facilities at the PCB, the PKB and the UB will be available.
The Beatriu de Pinós fellow will be integrated into the RP-RUBAM consortium, taking active part in the development and execution of the current project (see next section). Candidates with a solid background in molecular biology and/or chemical biology are sought, given the interdisciplinary nature of our research. The candidate will join an enthusiastic team, offering a stimulating and creative working atmosphere in one of the most scientifically active poles of research of the country.
4. PROJECT DESCRIPTION
Our research is aimed at the design and development of a novel class of proteolysis targeting chimeras (“protacs”). The concept of protacs has recently emerged as a new approach in drug discovery. The classical protacs are heterobifunctional molecules containing two ligands, one directed to the protein to be degraded (the protein of interest, POI) and another to the E3-ubiquitin-ligase (E3UbL) that is required for the POI ubiquitination and its subsequent targeting to the proteasome. In connection with this idea, we are currently developing a novel class of protacs capable of directly targeting the POI to the proteasome, thus bypassing the ubiquitination step. This approach is under development in our team with promising results. This strategy is intended to be applied to the degradation of essential POIs, whose degradation is expected to be of therapeutic relevance in a variety of fields, ranging from antiviral to metabolic regulators and anticancer agents. The methodologies applied in our projects comprise in silico techniques (docking, molecular dynamics, etc), synthesis and characterization of small molecules, general drug design principles, recombinant expression and isolation of protein complexes, protein turnover assays, determination of enzymatic and affinity constants, compound screening in cellular platforms, ubiquitin-proteasome pathway methods.
Post-doctoral fellows with a solid background in some of the above disciplines are suitable candidates for this application.
5. APPLICATIONS: DOCUMENTS TO BE SUBMITTED AND DEADLINE
If you are interested to apply to a Beatriu de Pinós BP2020 call to join our team, please send your CV and a cover letter to Bernat Crosas or Antonio Delgado. The deadline to receive the document will be 1st March 2021.
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