1. Research Background:
The escalating burden of obesity and Type 2 Diabetes Mellitus triggers an urge to further delineate the exact mechanisms that govern fundamental behavioral and physiological processes such as feeding or maintenance of steady body weight and glycemia. To build upon this challenge, our group is keen to deepen our understanding of the fundamental principles of the central control of metabolism from embryo to adult.
Our general interest is to decipher the exact neuronal networks controlling energy and glucose homeostasis by uncovering their precise functions and their developmental wiring.
Projects conducted in our group ultimately intent on furthering our understanding of the pathophysiology of obesity and Type 2 Diabetes Mellitus and to provide new insights regarding interventional approaches to tackle these metabolic diseases.
2. Research questions addresses by the group:
- We seek at further defining the architecture and the functional principles of neuronal-based circuits controlling energy and glucose homeostasis in adults. By doing so, we hope to better delineate how the brain controls metabolic processes and to identify the exact neurocircuits involved in these events. Our projects notably intend to understand how the organism senses and integrates its environment and adapt its behavior according to its physiological and nutritional needs.
- Metabolic disorders are increasingly diagnosed in childhood and have recognized roots in very early life. Indeed, compelling evidence from animals and epidemiological studies reveal that abnormal changes in the maternal, fetal, and neonatal environment substantially contribute to the onset of these metabolic diseases. Notably, changes in the nutritional and/or hormonal environment during gestation and/or lactation (e.g. maternal obesity/malnutrition or diabetes) can permanently alter the development of “brain-metabolic” pathways. Those alterations will in turn lead to life-long changes in homeostatic functions and predisposes individuals to develop metabolic diseases later in life.
3. Possible projects:
Possible Ph.D projects will therefore focus on:
- Studying the developmental programming of obesity and metabolic diseases by uncovering new mechanisms underlying the developmental programming of metabolic neuronal networks. The overarching goal will be to pinpoint novel brain-metabolic pathways sensitive to abnormal perinatal milieus that could ultimately contribute to the onset of metabolic dysfunctions, or
- defining further the exact neurocircuits controlling energy and glucose homeostasis in adults. The overall goal of this project will be to define the architecture and the functional principles of neuronal-based circuits controlling appetite in adults and investigate their role in the onset and the progression of obesity and its associated metabolic diseases
4. Applied Methods and model organisms:
The proposed Ph.D projects will be performed in mouse and will require the utilization of a broad range of techniques/approaches including:
- utilization of various transgenic mouse models
- utilization of mouse models of maternal programming
- assessment of the functionality of neurocircuit controlling metabolism (optogenetics, chemogenetics, in vivo calcium imaging...)
- behavioral assay
- in vivo physiology for the characterization of energy and glucose homeostasis
- RNA sequencing
- basic molecular biology
5. Desirable skills and qualifications:
Experience with mouse handling is preferred though not required.
- Steculorum SM, Ruud J, Karakasilioti I, Backes H, Engström Ruud L, Timper K, Hess M, Tsaousidou E, Mauer J, Vogt MC, Paeger L, Bremser S, Klein AC, Morgan DA, Frommolt P, Brinkkötter PT, Hammerschmidt P, Benzing T, Rahmouni K, Wunderlich FT, Kloppenburg P & Brüning JC. AgRP-neurons control systemic insulin sensitivity via myostatin-expression in brown-adipose tissue. Cell, 24;165(1):125-38. (2016)
- Ruud J, Steculorum SM, Brüning JC. Neuronal control of peripheral insulin sensitivity and glucose metabolism. Nat Commun. 4;8:15259. doi: 10.1038/ncomms15259. (2017)