Molecular tuning of sensory systems in octopus

所有生物都能感知并适应环境的变化。生物体状态的改变会导致 表观遗传学的变化，极大地影响了动物与环境的相互作用。生物体 基于他们的行为状态的剧烈改变感觉还没有被很好地理解。章鱼的感官 这些专家利用“触觉味觉”化学触觉与环境互动。这种感官 系统由专门的化学感受器（CR）介导，其检测难溶性分子，如 猎物分泌的如果长时间得不到猎物，章鱼是否会适应， 敏感的掠食者章鱼可能利用的一种机制是表观遗传腺苷到肌苷（A到I） 编辑.章鱼很容易通过交换腺苷来编辑mRNA转录本， 对于肌苷，其在翻译期间被解释为鸟苷。这个过程允许单个基因产生 具有潜在新功能的多种不同翻译蛋白。我将检验一个假设， 生物体状态偏向于优先的A到I编辑，以瞬时改变蛋白质序列和功能，并调节 对特定生物体状态最显著的环境信号的检测。这种机制可以 调整章鱼独特的化学触觉感觉系统，使其在饥饿时对猎物分子更敏感。这 该项目将利用从RNA生物学到动物行为的多方面方法，为我提供 有足够的机会学习新的概念，技术，并建立一个独立的轨迹遵循我的 博士后培训。我的多元化顾问团队将提供细胞生理学方面的专家指导（尼古拉斯·贝隆诺）， RNA生物学（Amy Lee）、通道结构-功能（Ryan Hibbs）和动物行为（Venkatesh Murthy）。在 在这些研究中，我将使用分子和生物化学方法来确定哪些CR是RNA编辑的目标 或者响应于不同的生物体状态而优先翻译，例如饥饿与进食（目标1）。我们 初步数据表明，章鱼在饥饿期间编辑CRs的蛋白质编码区。 在确定了CR变体的谱之后，我将描述重新编码的CR的生物物理特性， 未经编辑的CR，以确定状态依赖性编辑的功能后果（目标2）。我会集中 分析配体敏感性和离子渗透，这可以解释对猎物分子的敏感性增加 或者改变了神经信号最后，我将利用这些发现来了解急性编辑是如何进行的。 个别蛋白质影响适应性有机体感觉（目的3）。我会进行行为分析 蛋白质功能的特定变化是否与饥饿和进食章鱼的行为改变有关。 例如，如果饥饿诱导的CRs RNA编辑改变了对猎物分子的敏感性， 为了检测，我将测试化学诱导章鱼手臂运动的阈值。调查 有机体如何能够敏锐地调节蛋白质结构和功能以改变行为是新颖的， 对翻译、信号转导和进化机制的基本见解。

All organisms sense and adapt to changes in their environment. Alterations in organismal state can lead to epigenetic changes that dramatically influence how an animal interacts with its environment. How organisms acutely alter sensation based on their behavioral state is not well understood. Octopuses are incredible sensory specialists that use ‘taste by touch’ chemotactile sensation to interact with their environment. This sensory system is mediated by specialized chemotactile receptors (CRs) that detect poorly soluble molecules, such as those secreted by prey. If prey is unavailable for prolonged periods, do octopuses adapt to become more sensitive predators? One mechanism octopus might deploy to adapt is epigenetic adenosine to inosine (A-to-I) editing. Octopuses readily diversify their proteomes through editing mRNA transcripts by swapping adenosine for inosine, which is interpreted as a guanosine during translation. This process allows a single gene to produce multiple different translated proteins with potentially new functions. I will test the hypothesis that manipulation of organismal state biases preferential A-to-I editing to transiently alter protein sequence and function and modulate the detection of environmental signals most salient to the specific organismal state. Such a mechanism could tune the unique octopus chemotactile sensory system to be more sensitive to prey molecules when hungry. This project will utilize a multifaceted approach spanning from RNA biology to animal behavior, providing me with ample opportunity to learn new concepts, techniques, and establish an independent trajectory following my postdoctoral training. My diverse advisory team will provide expert guidance in cell physiology (Nicholas Bellono), RNA biology (Amy Lee), channel structure-function (Ryan Hibbs), and animal behavior (Venkatesh Murthy). In these studies, I will use molecular and biochemical approaches to identify which CRs are targets of RNA editing or are preferentially translated in response to distinct organismal states, such as starved versus fed (Aim 1). Our preliminary data demonstrate that octopuses edit protein-coding regions of CRs during periods of starvation. After identifying the spectrum of CR variants, I will characterize the biophysical properties of recoded CRs against unedited CRs to determine the functional consequences of state-dependent editing (Aim 2). I will focus my analysis on ligand sensitivity and ion permeation, which could account for increased sensitivity to prey molecules or altered neural signaling. Finally, I will leverage these discoveries to understand how the acute editing of individual proteins affects adaptive organismal sensation (Aim 3). I will carry out behavioral assays to test whether specific changes in protein function correlate with altered behavior across starved and fed octopuses. For example, if starvation-induced RNA editing of CRs alters sensitivity to prey molecules to enhance prey detection, I will test the threshold for chemically induced arm movement in behaving octopuses. Investigating how organisms can acutely regulate protein structure and function to alter behavior is novel and will provide fundamental insight into mechanisms of translation, signal transduction, and evolution.