Molecular tuning of sensory systems in octopus

章鱼感觉系统的分子调节

• 批准号: 10537518
• 负责人: Rebecka Jane Sepela
• 金额: $ 6.68万
• 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/10537518
• 关键词: Acute; Adaptive Behaviors; Adenosine; Advisory Committees; Affect; Amino Acid Sequence; Animal Behavior; Animals; Architecture; Behavior; Behavioral; Behavioral Assay; Biochemical; Biology; Biophysics; Cell physiology; Cells; Cephalopoda; Chemicals; Cryoelectron Microscopy; Data; Dependence; Detection; Electrophysiology (science); Environment; Enzymes; Epigenetic Process; Esthesia; Evolution; Exhibits; Family; Genes; Genetic Translation; Guanosine; Hour; Hunger; Individual; Inosine; Ion Channel; Ions; Lead; Learning; Ligands; Measures; Mediating; Messenger RNA; Molecular; Mutagenesis; Nervous system structure; Neurotransmitter Receptor; Octopus; Open Reading Frames; Organism; Pharmacology; Physiological; Polyribosomes; Process; Property; Proteins; Proteome; Proteomics; RNA; RNA Editing; RNA Sequences; Research; Ribosomes; Sensory; Sensory Receptors; Signal Transduction; Site; Specialist; Starvation; Stimulus; Structure; Taste Perception; Techniques; Testing; Touch sensation; Training; Transcript; Translating; Translations; Variant; adenosine deaminase; arm; arm movement; base; biophysical properties; epigenetic regulation; experimental study; flexibility; genomic RNA; insight; neurotransmission; novel; patch clamp; polypeptide; post-doctoral training; protein function; protein structure function; 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.

所有生物体都会感知并适应环境的变化。生物状态的改变可能会导致。 表观遗传变化极大地影响了动物与其环境的相互作用。 根据章鱼的行为状态急剧改变感觉的机制尚不清楚。 专家使用“触觉味觉”化学触觉与环境互动。 该系统由专门的趋化受体（CR）介导，可检测难溶性分子，例如 如果长时间没有猎物，章鱼会适应变得更多吗？ 章鱼可能采用的一种适应机制是表观遗传腺苷到肌苷（A 到 I） 章鱼可以通过交换腺苷来编辑 mRNA 转录本，从而轻松实现蛋白质组的多样化。 对于肌苷，它在翻译过程中被解释为鸟苷。这个过程允许单个基因产生。 我将测试具有潜在新功能的多种不同翻译蛋白质。 生物状态偏向优先 A 到 I 编辑，以瞬时改变蛋白质序列和功能并进行调节 这种机制可以检测对特定生物状态最重要的环境信号。 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加敏感。 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 学习新概念、技术并建立独立轨迹的样本机会 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·贝洛诺）， RNA 生物学（Amy Lee）、通道结构功能（Ryan Hibbs）和动物行为（Venkatesh Murthy）。 在这些研究中，我将使用分子编辑和生化方法来识别哪些 CR 是 RNA 的目标 或优先翻译以响应不同的生物状态，例如饥饿与饥饿（目标 1）。 初步数据表明，章鱼在饥饿期间会编辑 CR 的蛋白质编码区域。 在确定 CR 变体的范围后，我将针对重新编码的 CR 的生物物理特性进行表征 未经编辑的 CR 来确定状态相关编辑的功能后果（目标 2）。 配体敏感性和离子渗透分析，这可以解释对猎物分子敏感性增加的原因 最后，我将利用这些发现来了解如何进行急性编辑。 个别蛋白质会影响适应性生物感觉（目标 3）。 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相关。 例如，如果饥饿诱导的 CR RNA 编辑改变了对猎物分子的敏感性以增强猎物的能力 检测后，我将测试化学诱导的章鱼手臂运动的阈值以进行研究。 生物体如何敏锐地调节蛋白质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见解。