Liming Wang

Bowes Research Fellow

Lab Homepage: http://mcb.berkeley.edu/faculty/bmb/wangl.html

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Research Interests

Neural Regulation of Energy Homeostasis

The survival and well-being of animals rely on precisely maintained balance between energy intake and expenditure – in other words, the energy they get from food and the energy they consume to grow, to breath, and to move. The central nervous system (CNS) plays a crucial role in maintaining energy homeostasis. It determines the internal energy state and initiates or terminates energy intake accordingly. Moreover, the CNS is also able to detect various physiological and environmental conditions such as arousal and emotional states of animals and environmental risk, to adjust the energy intake behaviors. Despite its striking accuracy, however, the ability of the CNS to maintain energy homeostasis can be disrupted by sustained environmental challenges, including high fat diet, insomnia and stress, which may contribute to the pathogenesis of prevailing metabolic disorders in post-industrialized societies, such as obesity and type II diabetes. It is therefore of both scientific and clinical interest to elucidate the mechanism underlying the regulation of energy homeostasis by the CNS.

The organization of the CNS is overwhelmingly complex: the human brain is composed of ~10¹⁰ neurons, which can be classified to hundreds if not thousands of morphologically and functionally distinct subgroups. These neuronal subgroups may play very different or even opposite roles in regulating energy homeostasis. Therefore, a comprehensive understanding of the role of the CNS in regulating energy homeostasis requires: 1> a system with relatively "simplified" organization of the CNS; 2> a platform to reliably distinguish and manipulate individual neuronal subgroups; and 3> an assay(s) ensuring quantitative and straightforward assessment of energy/metabolic states.

The fruit fly Drosophila melanogaster offers several attractive advantages in this regard. Compared to human, it has a much smaller and simpler CNS with only ~200,000 neurons. Nevertheless, the key genetic and neural players in energy homeostasis are well conserved in flies. The powerful Gal4/UAS system and the available RNAi libraries and Gal4 collections together allow precise labeling and manipulation of genes and neuronal subgroups in a time- and cell type- specific manner. Moreover, fruit flies are comparably easier and cheaper to raise, and exhibit simpler behaviors, both of which make it more accessible for large-scale screens.

Our research interests focus on using the fruit fly as a model system to identify novel genetic and neural players in the regulation of energy homeostasis, and how they are involved in the pathogenesis of metabolic disorders. To this end, we are employing a combination of genetic, physiological, behavioral and biochemical approaches. We hope our work will shed important light on this fundamental yet less understood problem – how our brain helps to maintain a precise balance of the energy we absorb and consume, under which circumstances it fail, and why.

Coordination of Metabolic Changes at Organismal Level

Besides the CNS, various tissues/organs, including liver, pancreas, skeletal muscle, adipose tissue and autonomous nervous system, are responsive and adaptable to intrinsic and extrinsic metabolic changes. Importantly, the adaptations employed by different tissues/organs have to coordinate to achieve an appropriate and well-balanced response at the organismal level. In this regard, various tissues/organs have evolved elegant signaling systems for crosstalk (a famous example is leptin, which is released by adipose tissue and conveys the adiposity information to the brain).

We are interested in a more comprehensive understanding of the crosstalk scheme among different tissues/organs upon metabolic changes. How many signaling molecules like leptin are there? How are they released and sensed? How do they interact?

Our model system for this particular problem is zebrafish Danio rerio. We are currently developing quantitative metabolic assays that are suitable for large-scale genetic and small molecule screens. By doing these screens, we aim for the identification and characterization of novel signaling molecules that are important for the coordination of metabolic changes at the organismal level.

Selected Publications

Wang, L.*, Han, X., Mehren, J., Hiroi, M., Billeter, J-C., Miyamoto, T., Amrein, H., Levine, J. D. and Anderson, D. J.* (2011). Hierarchical chemosensory regulation of male-male social interactions in Drosophila. Nature Neurosci. 14, 757-762 (*co-corresponding authors)

Wang, L.* and Anderson, D. J.* (2010). Identification of an aggression-promoting pheromone and its receptor neurons in Drosophila. Nature 463, 227-231 (*co-corresponding authors)

Dankert, H., Wang, L., Hoopfer, E. D., Anderson, D. J. and Perona, P. (2009). Automated monitoring and analysis of social behavior in Drosophila. Nature Methods 6, 297-303

Wang, L., Dankert, H., Perona, P. and Anderson, D. J. (2008). A common genetic target for environmental and heritable influences on aggressiveness in Drosophila. Proc. Natl. Acad. Sci. USA 105, 5657-5663

Last Updated 2011-12-02