Molecular tuning of sensory systems in octopus

所有的有机体都能感知并适应环境的变化。生物体状态的改变可能会导致 表观遗传变化，极大地影响动物与环境的相互作用。生物体是如何 根据他们的行为状态来剧烈地改变感觉还没有被很好地理解。章鱼的感官能力令人难以置信 专家们利用“触觉味觉”的化学触觉与周围环境进行互动。这种感官 系统是由特殊的化学活性受体(CRS)介导的，它检测难溶的分子，如 那些由猎物分泌的东西。如果长时间无法获得猎物，章鱼是否会适应变得更多 敏感的捕食者？章鱼可能采用的一种适应机制是表观遗传的腺苷到肌苷(A到I) 正在编辑。章鱼很容易通过交换腺苷来编辑mRNA转录本，从而使其蛋白质组多样化 对于肌苷，在翻译过程中被解释为鸟苷。这一过程允许单个基因产生 多个不同的翻译蛋白具有潜在的新功能。我将检验这样一种假设，即操控 生物体状态偏向A-to-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。这样的机制可以 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 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，并按照我的 博士后培训。我的多元化咨询团队将提供细胞生理学方面的专家指导(尼古拉斯·贝洛诺) RNA生物学(艾米·李)、通道结构-功能(Ryan Hibbs)和动物行为(Venkatesh Murthy)。在……里面 在这些研究中，我将使用分子和生化方法来确定哪些CRS是RNA编辑的目标 或优先翻译成不同的生物体状态，如饥饿与进食(目标1)。我们的 初步数据表明，章鱼在饥饿期间编辑CRS的蛋白质编码区。 在鉴定了CR变异体的光谱后，我将针对 未编辑的CRS，以确定依赖状态的编辑的功能后果(目标2)。我会集中我的精力 配体敏感性和离子渗透性的分析，这可能是对猎物分子敏感性增加的原因 或者改变了神经信号。最后，我将利用这些发现来理解如何敏锐地编辑 个体蛋白质影响适应性的生物体感觉(目标3)。我会进行行为分析来测试 蛋白质功能的特定变化是否与饥饿和喂食章鱼的行为变化相关。 例如，如果饥饿诱导的CRS的RNA编辑改变了对猎物分子的敏感性，以增强猎物 检测，我将测试化学诱导章鱼手臂运动的阈值。调查 生物体如何敏锐地调节蛋白质的结构和功能以改变行为是新颖的，并将提供 对翻译、信号转导和进化机制的基本洞察。

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.