Clauda Abboud, awarded a Marie Skłodowska-Curie IF research grant for her project FEEDING
The FEEDING project: "Finding new target to modulate food intake", led by Clauda Abboud, post-doctoral fellow in the Molecular Pharmacology laboratory of the GIGA-Molecular Biology of Diseases (MBD) research centre and the Interdisciplinary Drug Research Centre (CIRM) of the ULiège University, aims to study the pharmacology of G Protein Coupled Receptors (GPCRs).
O
besity is a major public health burden as it increases the risk of several chronic diseases, such as diabetes, cardiovascular disease, musculoskeletal disorders or certain cancers. Energy homeostasis is centrally regulated by the hypothalamus, where the arcuate nucleus (ARC) orchestrates eating behaviour and energy balance. Two populations of neurons in the ARC are considered to be the first-order neurons mediating the effects of various signals such as leptin and insulin, the orexigenic neuropeptide (NP)Y/agouti-related peptide (AgRP) neurons and the anorexigenic pro-opiomelanocortin (POMC)/amphetamine-regulated transcript (CART) neurons. Leptin is a peptide hormone secreted by adipocytes that inhibits food intake and regulates body weight. In almost all forms of obesity, circulating leptin levels increase but fail to suppress food intake and body weight. This condition has been identified as "leptin resistance". G protein-coupled receptors (GPCRs) are the largest family of membrane proteins and a well-known source of drug targets. However, many GPCRs are understudied or even orphaned, i.e. they have no known ligands.
Despite our knowledge of the key pathways regulating feeding, satiety, hunger and energy expenditure, we have not been able to provide effective drugs targeting these systems. The failure to target the melanocortin pathways stems in part from an incomplete understanding of leptin action, particularly leptin resistance, at the central level. Here we propose to study the interaction between orphan GPCR signalling and the leptin receptor in leptin-sensitive cells of the arcuate nucleus. To do so, we will use conditional knockout animals and pharmacological modulators. We will measure various metabolic parameters, including weight and food intake, using the Comprehensive Laboratory Animal Monitoring System (CLAMS). We will also establish hypothalamic cell cultures in which we will study the impact of G protein signalling on leptin.
In her project, Clauda is studying orphan GPCRs (i.e. those with no known ligands) in the hypothalamus and, in particular, their role in the regulation of food intake and obesity. She hopes to validate these receptors as therapeutic targets in metabolic diseases.
Supervisor: Julien Hanson, Senior Research Fellow FRS-FNRS of the Faculty of Medicine, Molecular Pharmacology Laboratory, GIGA-Molecular Biology of Diseases (MBD)/Interdisciplinary Drug Research Centre (CIRM)
Marie Sklodowska-Curie Individual Fellowships
Marie Sklodowska-Curie Individual Fellowships are European postdoctoral fellowships of excellence awarded to outstanding researchers wishing to develop their scientific career through a mobility experience in Europe rich in scientific exchange and learning.
The University of Liège has already been awarded several dozen projects of excellence funded by this programme.
