03/05/2021
Marie Skłodowska-Curie Actions

MSCA-PF: Joint application at the University of Granada. Department of Pharmacology

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  • OFFER DEADLINE
    31/08/2021 09:00 - Europe/Brussels
  • EU RESEARCH FRAMEWORK PROGRAMME
    HE / MSCA
  • LOCATION
    Spain, Granada
  • ORGANISATION/COMPANY
    International Research Projects Office
  • DEPARTMENT
    Promotion and Advisory Unit
  • LABORATORY
    NA

Professor Fermín Sánchez de Medina from the Department of Quantitative Methods for Economics and Business at the University of Granada, welcomes postdoctoral candidates interested in applying for a Marie Skłodowska-Curie Postdoctoral Fellowships (MSCA-PF) in 2021 at this University. Please note that applicants must comply with the Mobility Rule (more information about the 2020 call: http://sl.ugr.es/0aNV, the 2021 call is not yet open).

Brief description of the institution:

The University of Granada (UGR), founded in 1531, is one of the largest and most important universities in Spain. With over 60.000 undergraduate and postgraduate students and 6.000 staff. UGR offers a total of 89 degrees, 110 master’s degrees and 28 doctoral programmes through its 123 departments and 27 centers. Consequently, the UGR offers one of the most extensive and diverse ranges of higher education programmes in Spain.

The UGR has 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. UGR is also a leading institution in research, located in the top 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 - Academic Ranking of World Universities (ARWU) (http://sl.ugr.es/0bsW). The UGR is amongst the 201-300 first universities of the world, between 2nd-5th position of Spanish universities and number 1 in the Andalusian Region in the Shanghai Top 500 ranking. Specialties at UGR that stand out are Library & Information Science (position 32) and Food Science & Technology (position 36). Moreover, the UGR is also situated amongst the first 100 universities in Mining & Mineral Engineering between (76th-100th position), in Mathematics (between 76th-100th position) and in Hospitality & Tourism Management (between 76th-100th position). The edition of the ARWU places the UGR in 201-300th 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.

Additionally, the UGR has 8 researchers at the top of the Highly Cited Researchers (HCR) list in Computer Sciences & Engineering (position 101-150). It is also well recognized for its web presence (http://sl.ugr.es/0a6i), being positioned at 43th 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 67 projects, with total funding of 18.029 million euros, and for H2020, 118 projects with total funding around 29.115 million euros.

Brief description of the Centre/Research Group:

Our research group works in the field of pathophysiology (ion transport, alkaline phosphatase, inflammatory markers) and pharmacology (flavonoids, glycomacropeptide, oligosaccharides, bisphosphonates, corticosteroids) of inflammatory bowel disease and obesity/metabolic syndrome. Central to both is an alteration of the function of intestinal barrier, a fundamental element of intestinal homeostasis involved in inflammatory processes such as inflammatory bowel disease, but also many other intestinal and systemic diseases, including metabolic syndrome, acute pancreatitis, liver disease, sepsis, etc.

We use various cellular models, including intestinal organoids, and animal models, such as KO mice for the intestinal epithelial glucocorticoid receptor Nr3c1 (developed by our group), haplodeficient mice for tissue nonspecific alkaline phosphatase (Alpl), immunodeficient mice Zucker rats, etc. The experimental techniques used include molecular techniques, FACS, immunohistochemistry, gene silencing, studies of electrolytic transport, metagenomics of fecal microbiota, pharmacogenomics, etc.

We have received about 650,000 € in the last 5 years, coming mainly from competitive public projects but also from contracts with companies and projects financed by foundations. Our group is a member of the Center for Biomedical Research in the Liver and Digestive Diseases Network (CIBERehd), which brings together the most prestigious groups active in the research of gastroenterology in Spain. Our publications profile is available at https://scholar.google.es/citations?user=Y0GzurEAAAAJ&hl=en

Project description:

Glucocorticoids (GC) are widely used drugs, mostly for inflammatory and/or autoimmune conditions. They are often highly efficacious and relatively fast compared to other immunosuppressants. However, their use, especially in a chronic setting, is linked to a substantial burden of adverse effects, plus GC dependence and refractoriness. They are widely used in the management of inflammatory bowel disease, where they are very useful in controlling inflammatory bouts but not in prolonging remission. Our group and others have shown that GC worsen overall status in animal models of colitis, despite amelioration of inflammation itself. We have established that these deleterious effects are related to the epithelial actions of GC, which result in debilitation of intestinal barrier function (IBF). This increases translocation of microbiota components, bacteria and fungi to the bloodstream, potentially enhancing systemic inflammation. Thus the limitations of GC in clinical practice may arise in part form the unfavourable epithelial actions of GC. In fact, endogenous GC may be at fault as well, as indicated by the transgenic model developed by us, i.e. NR3C1IEC-/- mice. Tamoxifen induced deletion of the GC receptor NR3C1 gives rise to colonic inflammation which subsides spontaneously. In turn, KO mice are protected against experimental colitis. The protective mechanism is related to both augmented epithelial proliferation and wound healing and to enhanced local steroidogenesis. Therefore we have provided proof of concept of improved outcome of GC treatment of colitis at the preclinical level in the absence of epithelial actions.

One of the objectives of this project is to perform an exhaustive search in publicly available databases linking colonic gene expression and clinical outcome in GC treated patients, in order to gather supportive evidence of our hypothesis. Furthermore, there are several other diseases amenable to GC treatment in which, similarly to inflammatory bowel disease, IBF may be weakened by the condition and by GC exposure. We intend to use our KO model to examine the hypothesis that the clinical management of systemic diseases may be limited by the intestinal epithelial actions of GC. The ultimate goal is to improve therapy by the use of GC agents or administration regimens/pathways that minimise epithelial actions. The diseases considered in this project are sepsis, acute pancreatitis and COVID19. In these 3 conditions IBF weakening has been identified as a contributing factor to pathology. We will use suitable in vivo models of sepsis and acute pancreatitis and will model the COVID19-related IBF alterations associated to the cytokine storm in this disease. We will additionally use in vitro models, mostly intestinal organoids, to characterise local steroidogenesis, as it is key in the phenotypes observed as noted, and any relevant differences of GC agents at this level. In summary, in this project we will (1) provide proof of concept about the harmful effect of GC actions at the intestinal epithelial level in systemic inflammatory diseases that involve weakening of the IBF in order to ultimately improve their clinical management; (2) explore differences in GC agents at the intestinal epithelial level; and (3) gather evidence that may support the deleterious impact of intestinal GC actions in the clinical arena.

Research Area:

  • Life Sciences (LIFE)

For a correct evaluation of your candidature, please send the documents below to Professor Fermín Sánchez de Medina (fsanchez@ugr.es):

  • CV
  • Letter of recommendation (optional)

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