KIN-29 SIK SIGNALING THE THEREGULATION OF FOOD-RELATED BEHAVIORS & DEVELOPMENT

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 在动物的环境中，食物的可获得性和质量随时间而波动。当食物缺乏时，动物必须在行为、新陈代谢和生理上发生变化，以促进生存。动物还必须根据营养状况调节其进食习惯，以保持生理稳态。盐诱导激酶（SIKs）是哺乳动物能量稳态和进食/禁食反应的重要调节因子。我们以前发现，KIN-29，C。elegans的同源物，调节化学感受器（CR）基因的表达，摄食行为和身体大小。我们相信，CR基因调节的基础，至少部分，动物的能力，以正确地识别食物来源的信号，以调节进食和身体大小。为了进一步剖析KIN-29信号通路，食物信号通过KIN-29信号通路被整合以调节行为和发育，我们正在采取三种并行策略来定义KIN-29的新靶点。首先，我们使用下一代测序结合mRNA标记方法确定特定感觉神经元的基因表达谱。使用微阵列的初步结果表明，预测在转录调控和磷酸化事件中起作用的基因的大子集分别在化学感觉神经元中的野生型和kin-29突变体中上调和下调。其次，我们正在研究KIN-29依赖性CR基因，其在ADL化学感觉神经元中的表达通过成年动物中食物的存在和不存在而急剧改变。我们将利用这些观察结果来确定食物信号改变CR基因表达的组件和神经元，使用遗传筛选。最后，我们将检查单个C的函数。CRTC/TORC的elegans同源物，其被SIK家族成员磷酸化，并且是哺乳动物和苍蝇中代谢的重要调节剂。总之，这些实验将提供食物对动物发育和行为的显着复杂的影响的详细了解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The availability and quality of food fluctuates over time in an animal's environment. When food is scarce, an animal must undergo changes in its behavior, metabolism and physiology to promote survival. An animal must also regulate its feeding habits depending on nutritional status in order to maintain physiological homeostasis. Salt-inducing kinases (SIKs) are important regulators of energy homeostasis, and feeding/fasting responses in mammals. We previously found that KIN-29, the C. elegans homolog of SIK, modulates chemoreceptor (CR) gene expression, feeding behaviors and body size. We believe that CR gene modulation underlies, at least in part, the ability of animals to correctly transduce food-derived signals to modulate feeding and body-size. To further dissect the KIN-29 signaling pathways by which food signals are integrated to modulate behavior and development, we are taking three parallel strategies to define new targets of KIN-29. In the first, we are determining the gene expression profiles of specific sensory neurons using next-generation sequencing coupled to a mRNA-tagging approach. Preliminary results using microarrays indicate that a large subset of genes predicted to function in transcriptional regulation and phosphorylation events are up- and down-regulated, respectively, in wild-type and kin-29 mutants in chemosensory neurons. Secondly, we are examining a KIN-29-dependent CR gene whose expression in the ADL chemosensory neurons is acutely altered by the presence and absence of food in adult animals. We will take advantage of these observations to identify the components and neurons by which food signals alter CR gene expression using genetic screens. Finally, we are examining the function the single C. elegans homolog of CRTC/TORC, which is phosphorylated by SIK family members and is an important regulator of metabolism in mammals and flies. Together these experiments will provide a detailed understanding of the remarkably complex effects of food on animal development and behavior.