Cell and Neurobiology
2100 København Ø
Research in my group is focused on steroid hormone and neuropeptide signaling that have important functions in development, reproduction, metabolism, behavior and diseases.
During development steroid signaling induces a switch from juvenile growth to sexual maturation. This is a tightly controlled process, requiring the assessment of checkpoints depending on nutrient levels and growth status to decide whether to release steroids that trigger maturation or continue juvenile development. Progression to the adult stage only occurs once the developmental timing program is aligned with checkpoints that activate neuroendocrine circuits promoting maturation-inducing steroid pulses. This flexibility allows animals to reach a genetically predetermined body size under different nutritional conditions by adjusting the duration of the juvenile growth period. The two important parameters are growth rate, controlled by insulin/IGF, and the duration of growth, determined by the release of steroids. To coordinate growth and maturation, insulin/IGF therefore converges on the neuroendocrine system to control timing of steroid release.
The basic strategy for regulating steroid signaling and the timing maturation is remarkably conserved in metazoans, from flies to humans. Together with the unparalleled genetic and molecular tools of the fruit fly Drosophila and the conservation of approximately 75% of human disease-related genes, this makes flies an attractive model. Drosophila is also a simple model because it has a limited number of signaling components and only one major steroid hormone produced in one specific tissue.
By using the genetic model system Drosophila, we aim to uncover cellular mechanisms and neuroendocrine circuits required for the regulation of steroid signaling. We are currently using molecular genetic approaches in combination with genome-wide RNAi, transcriptomic and proteomic strategies. Given the high degree of conservation, we believe that genetic studies on Drosophila will provide fundamental insight that may provide a paradigm for understanding how diseases, including metabolic disorders like obesity and diabetes, affect steroid signaling and timing of puberty in humans.
Animals also have to decide when and what to eat, depending on the quality of the food and the internal metabolic state to balance their calorie uptake and support growth. Drosophila do not eat more than needed to meet their metabolic requirements. Such complex behaviors are controlled by neural circuits that are involved in the evaluation of sensory inputs such as smell and taste in concert with internal nutrient status. How feeding behaviors are coordinated with metabolic programs is poorly understood. Another goal is to identify neuropeptides and neuronal circuits that underlie feeding behavior and metabolism. In a recent effort, we have identified a conserved neuropeptide that coordinate feeding and metabolic changes. This presumably allows external cues to be integrated with the internal physiological programs to balance their nutrient uptake. Identification of mechanisms controlling food intake and metabolism is important to provide basic insight about how these fundamental biological processes are controlled and help understand metabolic disorders in humans.