Molecular tuning of sensory systems in octopus

章鱼感觉系统的分子调节

• 批准号: 10678648
• 负责人: Rebecka Jane Sepela
• 金额: $ 6.91万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678648
• 关键词: Acute; Adaptive Behaviors; Adenosine; Advisory Committees; Affect; Amino Acid Sequence; Animal Behavior; Animals; Architecture; Behavior; Behavioral; Behavioral Assay; Binding; Biochemical; Biology; Biophysics; Cell physiology; Cells; Cephalopoda; Chemicals; Code; Cryoelectron Microscopy; Data; Dependence; Detection; Electrophysiology (science); Environment; Enzymes; Epigenetic Process; Esthesia; Evolution; Exhibits; Family; Floor; Genes; Genomics; Guanosine; Hour; Hunger; Individual; Inosine; Ion Channel; Ions; Learning; Ligands; Measures; Mediating; Messenger RNA; Molecular; Mutagenesis; Nervous System; Neurotransmitter Receptor; Octopus; Open Reading Frames; Organism; Physiological; Polyribosomes; Process; Property; Proteins; Proteome; Proteomics; RNA; RNA Editing; RNA Sequences; Research; Ribosomes; Sea; Sensory; Sensory Receptors; Signal Transduction; Site; Specialist; Starvation; Stimulus; Structure; Taste Perception; Techniques; Testing; Touch sensation; Training; Transcript; Translating; Translations; Variant; arm; arm movement; biophysical properties; dsRNA adenosine deaminase; epigenetic regulation; experimental study; flexibility; insight; mRNA Translation; neurotransmission; novel; patch clamp; pharmacologic; polypeptide; post-doctoral training; protein function; protein structure; receptor; receptor function; receptor sensitivity; response; sensory system; trait; transcriptomics; voltage

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.

所有生物都感知并适应其环境的变化。有机状态的改变可能导致 表观遗传变化极大地影响动物与环境相互作用。生物如何 基于其行为状态的急性改变感觉尚不清楚。章鱼是令人难以置信的感觉 使用“触摸品味”趋化感的专家与环境相互作用。这个感官 系统是由专门的趋化受体（CRS）介导的，该受体检测到固体分子差，例如 那些被猎物分泌的人。如果长时间不可用的猎物，请章鱼适应更多 敏感的掠食者？一种机制章鱼可能会部署以适应肌苷表观遗传腺苷（A-TO-I） 编辑。章鱼通过交换腺苷很容易通过编辑mRNA转录本来多样化其蛋白质组织 对于肌苷，在翻译过程中被解释为鸟苷。这个过程允许单个基因产生 具有潜在新功能的多个不同翻译的蛋白质。我将测试操纵的假设 有机状态偏见优先a-i编辑，以瞬时改变蛋白质序列和功能和调节 对特定有机状态最突出的环境信号的检测。这样的机制可以 调整独特的章鱼趋化感官感觉系统对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概念，技术并建立一个独立的轨迹 博士后培训。我的潜水员咨询团队将提供细胞生理学专家指导（Nicholas Bellono）， RNA生物学（Amy Lee），通道结构功能（Ryan Hibbs）和动物行为（Venkatesh Murthy）。 这些研究，我将使用分子和生化方法来识别哪些CR是RNA编辑的靶标 或优选地响应不同的有机状态（例如饥饿与饲料）进行翻译（AIM 1）。我们的 初步数据表明，在饥饿期间，章鱼编辑CRS的蛋白质编码区域。 在识别CR变体的光谱之后，我将表征重新编码CR的生物物理特性 未经编辑的CR确定国家依赖性编辑的功能后果（AIM 2）。我会集中精力 配体敏感性和离子渗透的分析，这可以解释对猎物分子的敏感性 或改变神经信号传导。最后，我将利用这些发现来了解如何急性编辑 单个蛋白质会影响自适应有机感觉（AIM 3）。我将进行行为分析进行测试 蛋白质功能的特定变化是否与饥饿和喂养的章鱼之间的行为改变相关。 例如，如果饥饿诱导的RNA编辑CRS会改变对猎物分子的敏感性，以增强猎物 检测，我将测试行为章鱼中化学诱导的手臂运动的阈值。调查 生物如何急性调节蛋白质结构和功能以改变行为是新颖的，并且将提供 对翻译，信号翻译和进化机制的基本洞察力。