Information processing in neuroendocrine circuits

In C. elegans and mammals, physiological processes such as ageing and metabolism are influenced by communication between signalling centres in the nervous system and other tissues. Presently, the precise neuroendocrine networks are not fully detailed. To detail these networks, we use computational and genomic approaches to identify molecular signals that modify ageing, development, and other aspects of physiology. We then pinpoint the cells from which they act and the target cells that they act on, to define the connectivity and topology of the signalling networks that control physiology. Our work focuses on conserved pathways that regulate ageing, metabolism, and other physiological processes. Thus, we anticipate that insights from our studies will reveal biological mechanisms relevant to human ageing, age-related diseases such as Alzheimer's and sarcopenia, as well as metabolic disorders such as obesity and type 2 diabetes.

Environmental and nutritional cues affect diverse aspects of physiology, but how these cues are interpreted by neuroendocrine networks is poorly understood. We use high-throughput quantitative fluorescence microscopy to investigate how environmental and nutritional information are relayed and integrated through these networks. Our computational analyses allows us to quantify the relationship between environmental inputs and neuron-specific gene expression in single animals over large populations. These approaches have identified intricate regulatory features that provide higher-order mechanisms for regulating the accuracy and redundancy of combinatorial gene expression codes in these neuroendocrine networks. Through this research, we expect to understand (1) how gene expression is used to process and integrate information from environmental and nutritional cues; (2) how these information processing steps are implemented and regulated; and (3) how the information encoded by changes in gene expression go on to influence lifespan and other physiological outputs. Because the principles of information processing are intrinsic to all physical systems, our discoveries will likely highlight fundamental mechanisms in diseases caused by defects in information processing, such as mental disorders.

Cold-blooded animals possess brains with a super-human ability – they function normally over a much larger temperature range.  A new study from the Ch’ng Lab, in collaboration with the Lu Lab at the Georgia Institute of Technology (USA), reveals how this ability is implemented in  C. elegans. Previously, these labs have unearthed a neural network that encodes food availability using gene activity, which in turn adjusts the animal’s lifespan according to the amount of food it encounters. Their latest discovery shows that this neural network can maintain the same performance at different temperatures. The roundworm’s ability to adapt to different food conditions at different temperatures has general implications for how flexible physiological processes can function normally in different environments, which is essential for survival.