Professor Mónica Díaz Gavilán, from the Department of Medicinal Chemistry and Organic Chemistry at the University of Granada, welcomes postdoctoral candidates interested in applying for a Marie Skłodowska-Curie Individual Fellowships (MSCA-IF) in 2020 at this University. Please note that applicants must comply with the Mobility Rule (more information: http://sl.ugr.es/0aNV).

Brief description of the institution:

The University of Granada (UGR), founded in 1531, is one of the largest and most important universities in Spain. The UGR has been awarded with the "Human Resources Excellence in Research (HRS4R)", which reflects the UGR’s commitment to continuously improve its human resource policies in line with the European Charter for Researchers and the Code of Conduct for the Recruitment of Researchers. The UGR is also a leading institution in research, located in the top 5/10 of Spanish universities by a variety of ranking criteria, such as national R&D projects, fellowships awarded, publications, or international funding.

UGR is one of the few Spanish Universities listed in the Shanghai Top 500 ranking (http://sl.ugr.es/0aw0). The Academic Ranking of World Universities (ARWU) places the UGR in 268th position in the world and as the 4th highest ranked University in Spain, reaffirming its position as an institution at the forefront of national and international research. From the perspective of specialist areas in the ARWU rankings, the UGR is outstanding in Documentation (ranked in the 36th in the world) or Food science technology (ranked 37th in the world), Mathematics and Computer Science (ranked among the top 76-100 in the world).

The UGR has 4 researchers at the top of the Highly Cited Researchers (HCR) list in the Computer Science area. With regard to broader subject fields, the UGR is ranked in 45th position in the universities worldwide in the discipline of Engineering. It is also well recognized for its web presence (http://sl.ugr.es/0a6i) taking 36th place in the top 200 Universities in Europe. Internationally, we bet decidedly by our participation in the calls of the Framework Programme of the European Union. For the duration of the last two Framework Programmes, the UGR has obtained a total of 66 projects, with total funding of 18.02 million euros, and for H2020, 80 projects with total funding around 20.6 million euros.

Brief description of the Centre/Research Group

The research will be developed within a group currently formed by four Lecturers, two Postdoctoral researchers and an undergraduate student. The research project will include drug design, organic synthesis, and biological screening of drugs.

The chemical part will be accomplished at the Faculty of Pharmacy in the Department of Medicinal Chemistry and Organic Chemistry. Our laboratories are fully equipped to carry out organic synthesis. This includes a microwave organic synthesis instrument, a hydrogenation apparatus, an HPLC, a LC-MS (single quadrupole, ESI), an IR instrument, a polarimeter, and a GC-FID. We have also recently acquired a computer server for in silico drug design. The NMR and the HRMS are provided by the Scientific Instrumentation Center (SIC) at the University of Granada (https://cic.ugr.es/).

The drug screening on recombinant enzymes and the enzyme kinetics determination will be conducted by researchers of our group at the SIC.

The project might include short research stays at the University of La Laguna (Spain), to perform drug screening on mouse hepatocyte primary cells, through the collaboration with Prof. Eduardo Salido.

Other collaborations we keep are with Prof. Angel Pey (University of Granada) for enzyme production and purification, Dr. José A. Gavira (Laboratory for Crystallographic Studies, Granada) for crystallography of enzyme-drug complexes, Dr. Juan R. Rodríguez (University of Navarra, Spain) for biological testing on human hepatocytes, and Prof. Sofía Salido (University of Jaén, Spain) for the synthesis of drug-carriers.

Project description

The main objective of this project is the development of small molecule drugs for the treatment of primary hyperoxalurias (PHs). This is a group of life-threatening genetic metabolic diseases, characterized by the accumulation of oxalate that leads to the systemic deposition of crystals. Due to the lack of an effective pharmacological treatment for PHs, big efforts are being made in this direction. Patients see their life hope and quality hampered. In the Spanish territory, Canary Islands present a high prevalence of PHs.

In this context, we work in the development of inhibitors of key enzymes in the metabolic route leading to the accumulation of oxalate. We have synthesized several hits with enzymatic and phenotypic activities in the low micromolar range [see for example J. Med. Chem. 2018, 61, 16, 7144- 7167]. We have also carried out enzyme kinetics and thus we have information about the inhibitory mechanisms of our compounds. An international patent has been filled that covers our previous work.

The synthesis of the novel drugs will be aimed at improving the potency in the human cell-based model of the disease and to obtain drugs that might be considered as leads. The candidate will be involved in the following aspects:

- Design of molecules, based in former structural and biological information, as well as using theoretical data obtained from in silico technologies.

- Synthesis and characterization of novel molecules.

- Biological screening, including production and purification of enzymes and development of enzyme kinetic protocols.

- Biological testing on cell cultures.

We expect the candidate will gain skills in the drug development process. Results will be published in highly ranked journals and communications will be held in international congresses.

Research Area

Life Sciences (LIFE)

For a correct evaluation of your candidature, please send the documents below to Professor Mónica Díaz Gavilán (monicadg@ugr.es):

• CV
• Letter of recommendation (optional)