The competition is open for the award of 1 type A post-doc research grant lasting 24 months, for the implementation of the activities reported below at the DIBIC to be carried out in the Medical Chemistry Lab under the supervision of Prof. Ottria.
Title: The endocannabinoid system as new target in Duchenne's muscular dystrophy: getting inside the mechanistic and the anti-inflammatory aspects.
Duchenne muscular dystrophy (DMD) is a complex disease characterized by skeletal muscle degeneration, strong inflammation and oxidative stress. Glucocorticoids provide a delay in the disease progression, unfortunately, their long-term use produces severe side effects. This highlights the need to develop alternative therapeutic strategies. The emerging literature suggests that the endocannabinoid system (ECS) plays an important role in the cellular differentiation and self-renewal capacity of skeletal muscle however, only few studies have been performed on DMD. Consequently, an in-depth ECS characterization and exploration of the role of its different components in skeletal muscle DMD pathophysiology is needed. The aim of this study is to explore for the first time the potential use of ECS modulators as co-adjuvant and/or treatment in DMD. We will i) characterize the ECS in a DMD mouse model; ii) explore the effects of ECS signaling lipids tone modulation on muscle differentiation and inflammation.
The project plans:
- Characterization of the expression of the ECS components (receptors and enzymes) by RT-qPCR in gastrocnemius, diaphragm, tibialis anterior and quadriceps muscles from male mdx and control mice.
- Synthesis and characterization of small organic molecules as modulators of the endocannabinoids hydrolytic enzymes activity.
- Evaluation of the effects of ECS hydrolytic enzymes modulators on the differentiation and inflammatory state of satellite cells from hind limb skeletal muscles of mdx mice.
- Evaluation of the ability of FAAH, MAGL, NAAA modulation to counteract macrophage activation and control M1-M2 switching will.
Required Skills:
Experience in laboratory techniques commonly used in the biochemical and molecular biology fields such as use of micropipettes, plate readers, ELISA kits.
Experience in handling cell cultures
Experience (comprising educational laboratories) in the synthesis and purification of small organic molecules (additional value)