28/03/2022
Marie Skłodowska-Curie Actions

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


  • OFFER DEADLINE
    30/09/2022 14:00 - 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 Pharmacology at the University of Granada, welcomes postdoctoral candidates interested in applying for a Marie Skłodowska-Curie Postdoctoral Fellowship (MSCA-PF) in 2022 at this University. Please note that applicants must comply with the Mobility Rule (for more information about the 2022 call, please consult: http://sl.ugr.es/0cmA).

Brief description of the institution:

The University of Granada (UGR) was founded in 1531 and is one of the largest and most important universities in Spain. With over 60,000 undergraduate and postgraduate students and 6,000 members of staff, the UGR offers over 70 undergraduate degrees, 100 master’s degrees (9 of which are international double degrees) and 28 doctoral programmes via its 127 departments and 22 centers. Accordingly, the UGR offers one of the most extensive and diverse ranges of higher education programmes in Spain.

The UGR has been awarded with the "Human Resources Excellence in Research (HRS4R)", which reflects the institution’s commitment to continuously improving 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 internationally renowned for its excellence in diverse research fields and ranked among the top Spanish universities in a variety of ranking criteria, such as national R&D projects, fellowships awarded, publications, and international funding.

The UGR is one of the few Spanish Universities listed in the Shanghai Top 500 ranking - Academic Ranking of World Universities (ARWU). The 2021 edition of the ARWU places the UGR in 201-300th position in the world and as the second highest ranked university in Spain (http://sl.ugr.es/0cmF), reaffirming its position as an institution at the forefront of national and international research. The UGR stands out in the specialties of Library & Information Science (position 36); Food Science & Technology (39) and Hospitality & Tourism Management (51-75), according to the latest edition of this prestigious ranking by specialties (http://sl.ugr.es/0bSp). A little lower in the ranking, the UGR also stands out in Mathematics (76-100) and Mining & Mineral Engineering (76-100).

Additionally, the UGR has 7 researchers who are at the top of the Highly Cited Researchers (HCR) list (http://sl.ugr.es/0cmD), most of these related to the area of Computer Science. It is also well recognized for its web presence (http://sl.ugr.es/0a6i), being positioned at 54th place in the top 200 Universities in Europe.

Internationally, the University of Granada is firmly committed to its 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, 119 projects with a total funding of around 29.233 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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