Prof. Dr. Jens C. Brüning

Research Area: Neuronal Control of Metabolism and Ageing

Branches: GeneticsMolecular BiologyNeurobiology

Website: Brüning Lab

1. Research Background:

The Central Nervous System (CNS) is constantly instructed about the energy state of the organism viahormonal and nutritional signals. It then coordinately regulates a wide array of behavioral and autonomic responses to adapt energy intake, energy expenditure, and nutrient flux across different organs, according to energy availability of the organism. Dysregulation of these homeostatic circuits causes prevalent diseases,such as obesity and type-2 diabetes mellitus, which are on an epidemic rise in industrialized societies. The overall aim of our research group is to unravel the fundamental regulatory principles of how neurons sense nutritional cues and then to determine the neurocircuitry responsible for the coordinated adaptation of behavioral and autonomic outputs. The ultimate aim of our research is to discover novel therapeutic targets for the development of treatment of metabolic disorders.

2. Research questions addresses by the group:

How are neurons in the hypothalamus instructed about the energy state of the organism and how do they integrate anticipatory signals of upcoming changes in energy state? How do neurons coordinate an integrative physiological response in accordance to changes in energy availability?

Our laboratory has taken a multifaceted approach to address these key questions. First, we have employed state-of-the-art technologies in molecular systems neuroscience to identify molecularly defined neuronal populations in control of food intake, systemic glucose homeostasis and related physiological processes. Second, we define the neurocircuitry architecture, how these cells integrate homeostatic and anticipatory signals. Third, we define the output circuitries, which ultimately execute communication with peripheral organs. Fourth, we define the molecular basis of disease-associated alterations in the activity of these neurocircuits as well as in peripheral target tissues.

3. Possible projects:

Some of the questions/projects we are pursuing include:

  • How does the CNS regulate feeding responses?
  • How does the CNS regulate peripheral glucose metabolism?
  • How do fuel sensing neurons control proteostasis in peripheral tissues?
  • How are anticipatory signals integrated in fuel sensing neurocircuits to prime organism adaptation?
  • What are the mechanisms of obesity- and ageing-associated de-regulation in these pathways?

4. Applied Methods and model organisms:

  • Model Organisms: Transgenic mouse models
  • Methods: Genetics, microscopy, mass spectrometry, molecular biology, systems biology (transcriptomics, proteomics, metabolomics), biochemistry, molecular systems neuroscience, optogenetics, Ca-imaging in vivo.

5. Desirable skills and qualifications:

Neuroscience, molecular biology and genetics

6. References:

  • Chen W, Mehlkop O, Scharn A, Nolte H, Klemm P, Henschke S, Steuernagel L, Sotelo- Hitschfeld T, Kaya E,Wunderlich CM, Langer T, Kononenko NL, Giavalisco P, Brüning JC. Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation. Cell Metab. 2023 May 2;35(5):786-806.e13. doi: 10.1016/j.cmet.2023.03.019. Epub 2023 Apr 18. PMID: 37075752
  • Gaziano I, Corneliussen S, Biglari N, Neuhaus R, Shen L, Sotelo-Hitschfeld T, Klemm P, Steuernagel L, De Solis AJ, Chen W, Wunderlich FT, Kloppenburg P, Brüning JC. Dopamine-inhibited POMCDrd2+ neurons in the ARC acutely regulate feeding and body temperature. JCI Insight. 2022 Nov 8;7(21):e162753. doi: 10.1172/jci.insight.162753. PMID: 36345942
  • Steuernagel L, Lam BYH, Klemm P, Dowsett GKC, Bauder CA, Tadross JA, Hitschfeld TS, Del Rio Martin A,Chen W, de Solis AJ, Fenselau H, Davidsen P, Cimino I, Kohnke SN, Rimmington D, Coll AP, Beyer A, YeoGSH, Brüning JC. HypoMap- a unified single-cell gene expression atlas of the murine hypothalamus. Nat Metab. 2022 Oct;4(10):1402-1419. doi:10.1038/s42255-022-00657-y. Epub 2022 Oct 20. PMID: 36266547
  • Porniece Kumar M, Cremer AL, Klemm P, Steuernagel L, Sundaram S, Jais A, Hausen AC, Tao J, Secher A, Pedersen TÅ, Schwaninger M, Wunderlich FT, Lowell BB, Backes H, Brüning JC. Insulin signalling in tanycytes gates hypothalamic insulin uptake and regulation of AgRP neuron activity. Nat Metab. 2021Dec;3(12):1662-1679. doi: 10.1038/s42255-021-00499-0. Epub 2021 Dec 20. PMID: 34931084
  • Biglari N, Gaziano I, Schumacher J, Radermacher J, Paeger L, Klemm P, Chen W, Corneliussen S,Wunderlich CM, Sue M, Vollmar S, Klöckener T, Sotelo-Hitschfeld T, Abbasloo A, Edenhofer F, Reimann F, Gribble FM, Fenselau H, Kloppenburg P, Wunderlich FT, Brüning JC. Functionally distinct POMC-expressing neuron subpopulations in hypothalamus revealed by intersectional targeting. Nat Neurosci. 2021Jul;24(7):913-929. doi: 10.1038/s41593-021-00854-0. Epub 2021 May 17. PMID: 34002087