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

Professor Ahmad Agil Abdalla, 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 2023 at this University. Please note that applicants must comply with the Mobility Rule (for more information about the 2023 call, please consult:(http://sl.ugr.es/0d7F).

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 51,000 undergraduate and postgraduate students and almost 3,000 members of staff, the UGR offers over 90 undergraduate degrees, 160 master’s degrees (8 of which are international double degrees) and 28 doctoral programmes via its 124 departments and nearly 50 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 2022 edition of the ARWU places the UGR in 201-300th position in the world and as the 2-5 highest ranked universities in Spain (http://sl.ugr.es/0d7D), 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 38); Food Science & Technology (30) 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).

Additionally, the UGR has 9 researchers who are at the top of the Highly Cited Researchers (HCR) list (http://sl.ugr.es/0d7E), 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 42th 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 Framework Programme, Horizon 2020, the UGR obtained a total 120 projects with a total funding of around 29,4 million euros.  For the current Framework Programme, Horizon Europe, the UGR has obtained 38 projects, so far, with total funding around 11 € million.

Brief description of the Centre/Research Group:

We are a Research Group that has been studying the evaluation of new strategies in the treatment of diabesity (obesity & diabetes) & its complication. Our main challenge is the application of bioactive agents & others in the field of medicine, especially diabestiy in those situations involving increased oxidative stress, mitochondrial damage, endoplasmic reticle, and associated meta-inflammation.

Project description:

Obesity is the largest out-of-control global pandemic affecting all cultural classes and populations of all economic levels with a brutal health impact and socioeconomic burden. The search for effective and safe drugs to control it has been unsuccessful. Melatonin has antioxidant and anti-inflammatory properties and an anti-obesogenic effect mediated by activation of non-shivering thermogenesis (NST) of brown and beige adipose tissues, and without affecting locomotor activity. However, both of these thermogenic mechanisms alone appear to be insufficient to justify the 12% reduction in body weight caused by melatonin. This suggests a thermogenic action in another organ, the musculoskeletal being the best candidate for its greater contribution to weight loss by NST tested in rodents. Additionally, the origin of intramuscular fat meta-inflammation is associated with obesity. The musculoskeletal and its associated intramuscular fat may be important targets for the muscle thermogenic and anti-inflammatory action of melatonin respectively. The mitochondria and the muscular endoplasmic reticulum constitute more than 50% of the cell volume, both being the major store of calcium (Ca2+). In fact, there are indications that melatonin could restore organellar Ca2+ homeostasis (mitochondrial and endoplasmic reticulum-ER). As a consequence of cellular damage and oxidative stress associated with obesity and its diabetes, these organelles are altered in muscle tissue (Ca2+-ATPase (SERCA)-sarcolipin (SLN) uncoupling and Ca+2 homeostatic dysregulation) and, in addition, an increase in low-grade inflammation in intramuscular fat. SLN is an uncoupler of SERCA activity responsible for thermogenesis generated by this pump. Our aim is to evaluate the effects of melatonin on the organelle-molecular mechanisms of musculoskeletal non-shivering thermogenesis regulated by SERCA-SLN-regulated musculoskeletal intra-organellar Ca2+ homeostasis and, additionally, the regulation of intramuscular fat meta-inflammation in the obese diabetic Zücker rat (ZDF), an experimental model of obesity and diabetes very similar to "human type 2 diabesity". Rats will be treated with oral melatonin (10 mg/kg/day) for 12 weeks and its effects on: 1. Thermogenic activity of the ZDF rat: a) Basal energy expenditure (Indirect Calorimetry), b) Muscle local (Thermography); 2. Muscle thermogenesis dependent on intra-endoplasmic reticulum Ca2+ homeostasis: a) intra-mitochondrial and -endoplasmic reticulum Ca2+ levels, b) activity and expression of SERCA of the ZDF rat, c) expression of thermogenic genes (SLN, PGC1a, NRF1/2) in ZDF rat muscle tissue, d) regulation of Ca2+-dependent thermogenic molecular pathways; 3. The bioenergetics, biodynamics and integrity of isolated muscle tissue mitochondria: a) mitochondrial respiration, b) enzymatic activity of complexes I and IV, c) ATP production, d) citrate synthase synthesis, e) free radical production, f) expression of fusion and fission markers (Drp1, Fis1, Opa1 and Mfn2) and g) mitochondrial integrity by Ca2+ retention; and 4. The inflammatory balance of intramuscular fat (expression of inflammatory markers) and cellular infiltration (IL-6, IL-8, MIP-1β, CRP, M-CSF and T4/8) of the ZDF rat. The ultimate goal of the project is to substantiate the potential use of melatonin for the treatment of human obesity.

Research Area:

• Life Sciences (LIFE)

For a correct evaluation of your candidature, please send the documents below to Professor Ahmad Agil Abdalla , email: aagil@ugr.es

• CV
• Letter of recommendation (optional)