Expression of Interest MSCA PF 2021. Multivalent Systems for Nanomedicine (MS4N). IQAC-CSIC

THE RESEARCH CENTER

The Institute for Advanced Chemistry of Catalonia (IQAC) belongs to the Spanish National Research Council (CSIC), the largest public research institution in Spain and the third among Europe’s largest research organisations.

The IQAC is located in Barcelona and it was created with the mission to perform multidisciplinary research of excellence in both basic and applied chemical sciences with the main purpose of improving the quality of life.

The research carried out at IQAC is based on the application of chemical approaches to address and solve societal challenges, mainly those related to human health, the sustainability of chemical processes and products, and the needs for novel materials for different applications. In this regard, the research programs carried out in our institute are aimed at:

• the development of methods and strategies for the synthesis of molecules of high added value (Methods & Strategies)
• the discovery of chemical and molecular entities of therapeutic, biological and biomedical interest (Tools & Hits)
• the study of molecules with surfactant properties, including synthesis, biophysical studies and applications (Surfactants)
• the generation and use of nanobiotechnology knowledge for the prevention, diagnostic and treatment of diseases (Nanomedicine).

Administratively, the research groups at IQAC are organized in two departments: Biological Chemistry, and Surfactants and Nanobiotechnology. Moreover, research is complemented with a range of diverse scientific and technical platforms (including cell culture and animal facility), which offer their capabilities to both internal and external users.

THE RESEARCH GROUP

Multivalent Systems for Nanomedicine (MS4N)

Supervisor: Miriam Royo

Contact: miriam.royo@iqac.csic.es

Web page:

• Multivalent Systems for Nanomedicine

Keywords: GPCRs oligomerization, Parkinson, Restless syndrome, spinal medular lesions, bivalent ligands, medicinal chemistry, drug delivery, cancer, drug-conjugates, targeting units

Research lines

Chemical Multivalent Systems are molecules containing multiple functional groups disposed on spatial distributions that are directly associated to their skeleton/scaffold architecture. These functional groups can be modified, in a controlled manner, with diverse biomolecules, drugs or ligands. Due to this versatility, multivalent systems become chemical tools with great potential in areas as chemical biology and nanomedicine, such as drug delivery, diagnosis and biomaterials.

Our group explore the use of diverse types of chemical multivalent platforms (oligomers, dendrimers, polymers, micelles and lipid nanovesicles), in:

1. Bivalent and multivalent ligands as pharmacological and therapeutic tools for the study of GPCR oligomerization, specifically A2AR, D2R, A1R and D1R oligomerization. Application to the development of a novel treatment for movement disorders, as Parkinson’s syndrome, spinal cord injury and restless legs syndrome.

GPCRs are involved in the regulation of many physiological processes and it is now widely accepted that these receptors form, in addition to functional monomers, dimers and higher-order oligomers. The relevance of these oligomers is that they present functional properties different from those of the constituent monomers and this makes them potential new therapeutic targets. Our group is focused on the development of chemical tools to study the oligomerization of adenosine and dopamine receptors, specifically A_2AR-D₂R y A₁R-D₁R oligomers, involved in movement disorders associated with diseases such as Parkinson, spinal cord injuries or restless legs syndrome. Mainly we are working in the design and synthesis of several multivalent platforms (bi-, tri- and tetravalent), functionalized with ligands, both agonists and antagonists, to be used as chemical tools that allow the characterization of these receptors and the evaluation of their potential therapeutic efficacy in the abovementioned pathologies.

2. Targeted and non-targeted drug-delivery systems for mono and combination therapy for the treatment of advanced colorectal cancer and triple negative breast cancer.

Tumors display a heterogeneous population of cells and among these are the cancer stem-like cells (CSC). Some models suggest that these cells, with self-renewal and multi-lineage differentiation capacities, are the main responsible for metastases and relapses. For this reason, classical chemotherapy, mainly directed to primary tumor cells, is sometimes not enough for the treatment of some types of cancer. The presence of CSC has been described in a variety of cancers, such as breast cancer and colorectal cancer. Our group explore the use of multivalent platforms based on polyglutamic acid-drug conjugates and drug-oligoethylene glycol micelles as drug delivery systems for the treatment of advanced colorectal cancer (mCRC) and triple negative breast cancer (TNBC). The aim is to prepare drug delivery systems containing a combination of different drugs linked covalently through sensitive linkers to microenvironment stimulus directed to both primary tumor cells and CSC. Furthermore, targeting molecules (peptides, metabolites) will be incorporated to these platforms to enhance their accumulation in tumor tissues.

What we are looking for is a candidate/s that should have expertise in some of these fields:

- Organic synthesis

- Conjugation chemistry

- NMR, HPLC and mass spectrometry analysis.

-Experience in purification process (Solid phase extraction, flash chromatography, semprep HPLC)

Will be also valued:

- Cell and biochemistry knowledge.

APPLICATIONS

The MSCA PF supports experienced researchers from any country in the world who:

• have a doctoral degree
• have a maximum of 8 years of full-time equivalent research experience*
• comply with the mobility rule: the applicant must not have resided or carried out his/her main activity (work, studies, etc.) in the country of the beneficiary for more than 12 months in the last three years immediately before the call deadline
• Only one proposal per individual researcher may be submitted to the MSCA PF 2021 call

*Information still subject to change. The final MSCA Work Programme is not published yet (MSCA PF 2021 call is expected to open in April 2021 and close in September 2021)

The MSCA Postdoctoral Fellowships provide living allowance (one to two years’ salary), mobility (and family) allowance, as well as research, training and networking costs and overheads for the host institution. The applicants submit proposals for funding jointly with the host organisation. Proposals are evaluated based on their research quality, the researcher's future career prospects, and the support offered by the host organisation. All domains of research and technological development are eligible for funding.

If you are interested in submitting an Expression of Interest, please send your CV, a motivation letter explaining your research background and interest and a summary of your project idea by 15^th May 2021 to the group supervisor indicating Expression of Interest MSCA PF 2021 in the subject.

The selected candidates will be invited to prepare a MSCA PF application and will receive help and support from our International and European Programme Unit during proposal preparation.