Background:

Novel weight-loss agents have shown considerable promise in addressing the obesity epidemic and its associated metabolic complications. While their primary mechanism of action is appetite suppression leading to reduced caloric intake, emerging evidence suggests that some compounds may also influence energy expenditure and metabolic health through direct effects on peripheral tissues, including adipose tissue, skeletal muscle, and liver.

Objective:

This thesis project focuses on the role of novel mitochondrial modulators in metabolic organs and their impact on metabolic function in the context of obesity. Based on preliminary experiments we have established significant protection from diet-induced obesity and glucose intolerance in mice with this completely new class of weight loss molecules. We now seek to decipher the specific underlying molecular mechanisms underlying this metabolic phenotype.

Techniques:

The proposed thesis provides hands-on training in state-of-the-art techniques in transcriptional biology, metabolism, and adipocyte biology. The project offers exposure to advanced molecular approaches, including transcriptomic and lipidomic analyses, primary pre-adipocyte isolation, adipocyte cell culture and differentiation, as well as comprehensive gene and protein expression analyses.

The candidate will gain experience with a broad range of in vitro and ex vivo metabolic assays in adipocytes and other metabolically active tissues. These include cellular respiration measurements using Seahorse extracellular flux analysis, assessment of mitochondrial function, and a variety of protein biochemistry techniques such as Western blotting and immunoblot-based analyses.

In addition, the project involves studies in diet-induced obesity mouse models, providing training in whole-body metabolic phenotyping including metabolic cage experiments to assess energy expenditure, substrate utilization, food intake, physical activity, thereby integrating molecular and organismal approaches to investigate mechanisms underlying the metabolic phenotype.

Qualification:

Masters Degree in Life Sciences such as Biomedical Sciences, Food Science and Biotechnology, Molecular Biology or similar field. Applicants should have a basic understanding of transcriptional biology and preferably some initial experience in cell culture, standard molecular biology techniques such as RNA and protein preparation, qPCR, and western blot. Experience in mouse handling would be ideal but is not mandatory.

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