1. Research Background:
The Central Nervous System (CNS) is constantly instructed about the energy state of the organism via hormonal 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. Moreover, we aim to identify molecular and physiological mechanisms for alterations in these pathways during the development of obesity and type-2 diabetes mellitus.
2. Research questions addresses by the group:
Our work aims at elucidating the role of hypothalamic neurocircuits in control of behavioural response and peripheral tissue function in control of metabolic homeostasis and aging. We are also working on defining the role of non-cell autonomous regulation in control of aging.
3. Possible projects:
- Hypothalamic control of non-cell autonomous UPR-regulation
- Functional neurocircuits in the regulation of systemic stress responses
4. Applied Methods and model organisms:
- State-of the art transgenic mouse models
- molecular systems neuroscience, i.e. optogenetics, chemogenetics, neurocircuit mapping
- systemic screens, transcriptomics, phosphoproteomics, lipidomics
- Functional tests in vitro
5. Desirable skills and qualifications:
- Strong interest in CNS dependent control of aging and disease
- High motivation and ability of critical thinking
- Ideally background in neuroscience
- Brandt C, Nolte H, Henschke S, Engström Ruud L, Awazawa M, Morgan DA, Gabel P, Sprenger HG, Hess ME, Günther S, Langer T, Rahmouni K, Fenselau H, Krüger M, Brüning JC. Food Perception Primes Hepatic ER-Homeostasis via Melanocortin-Dependent Control of mTOR-Activation. (2018) Cell (in press).
- Awazawa M, Gabel P, Tsaousidou E, Nolte H, Krüger M, Schmitz J, Ackermann PJ, Brandt C, Altmüller J, Motameny S, Wunderlich FT, Kornfeld JW, Blüher M, Brüning JC. A microRNA screen reveals that elevated hepatic ectodysplasin A expression contributes to obesity-induced insulin resistance in skeletal muscle. (2017) Nat Med. Dec; 23(12):1466-1473.
- Riera CE, Tsaousidou E, Halloran J, Follet P, Hahn O, Pereira MMA, Engström Ruud L, Alber J, Tharp K, Anderson CM, Brönneke HS, Hampel B, de Magalhaes Filho CD, Stahl A, Brüning JC*, Dillin A*. The sense of smell impacts metabolic health and obesity. (2017) Cell Metab. Jul 5; 26(1):198-211. *communicating authors
- Theurich S, Tsaousidou E, Hanssen R, Lempradl A, Mauer J, Timper K, Schilbach K, Folz-Donahue K, Heilinger C, Sexl V, Pospisilik JA, Wunderlich FT, Brüning JC. IL-6/Stat3-Dependent Induction of a Distinct, Obesity-Associated Natural Killer Cell Subpopulation Deteriorates Energy and Glucose Homeostasis. (2017) Cell Metab. Jul 5;26(1):171-184.
- Burnett CJ, Li C, Webber E, Tsaousidou E, Xue SY, Brüning JC, Krashes MJ. Hunger-Driven Motivational State Competition. (2016) Neuron Oct 5;92(1):187-201.
- Jais A, Solas M, Backes H, Chaurasia B, Kleinridders A, Theurich S, Mauer J, Steculorum SM, Hampel B, Goldau J, Alber J, Förster CY, Eming SA, Schwaninger M, Ferrara N, Karsenty G, Brüning JC. Myeloid-cell-derived VEGF maintains brain glucose uptake and limits cognitive impairment in obesity. (2016) Cell May 5; 165(4):882-895.
- Steculorum SM, Ruud J, Karakasilioti I, Backes H, Engström Ruud L, Timper K, Hess M, Tsaousidou E, Mauer J, Vogt M.C, Paeger L, Bremser S, Klein AC, Morgan DA, Frommolt P, Brinkkötter PT, Benzing T, Rahmouni K, Wunderlich T, Kloppenburg P, Brüning JC. AgRP-neurons control systemic insulin sensitivity via myostatin-expression in brown-adipose tissue. (2016) Cell Mar 24;165(1):125-138.
- Steculorum SM, Paeger L, Bremser S, Evers N, Hinze Y, Idzko M, Kloppenburg P, Brüning JC. Hypothalamic UDP Increases in Obesity and Promotes Feeding via P2Y6-Dependent Activation of AgRP Neurons. (2015) Cell Sep 10;162(6):1404-17.
- Mauer J, Chaurasia B, Goldau J, Vogt MC, Ruud J, Nguyen KD, Theurich S, Hausen AC, Schmitz J, Brönnecke H, Estevez E, Allen TL, Mesaros A, Partridge L, Febbraio MA, Chawla A, Wunderlich FT, Brüning JC. Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin (2014) Nat. Immunol. (15): 423–430
- Vogt MC, Paeger L, Hess S, Steculorum SM, Awazawa M, Hampel B, Neupert S, Nicholls HT, Mauer J, Hausen AC, Predel R, Kloppenburg P, Horvath TL, Brüning JC. Neonatal Insulin Action Impairs Hypothalamic Neurocircuit Formation in Response to Maternal High-Fat Feeding. (2014) Cell Jan 30;156(3):495-509.