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Influence of Alzheimer's Disease Related Neuropathology on Local Microenvironment Gene Expression in the Human Inferior Temporal Cortex 阿尔茨海默病相关神经病理对人类下颞叶皮层局部微环境基因表达的影响
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-10-01 DOI: 10.1089/genbio.2023.0019
Sang Ho Kwon, Sowmya Parthiban, Madhavi Tippani, Heena R. Divecha, Nicholas J. Eagles, Jashandeep S. Lobana, Stephen R. Williams, Michelle Mak, Rahul A. Bharadwaj, Joel E. Kleinman, Thomas M. Hyde, Stephanie C. Page, Stephanie C. Hicks, Keri Martinowich, Kristen R. Maynard, Leonardo Collado-Torres
Neuropathological lesions in the brains of individuals affected with neurodegenerative disorders are hypothesized to trigger molecular and cellular processes that disturb the homeostasis of local microenvironments. Here, we applied the 10x Genomics Visium Spatial Proteogenomics (Visium-SPG) platform, which couples spatial gene expression with immunofluorescence (IF) protein co-detection, to evaluate its ability to quantify changes in spatial gene expression with respect to amyloid-beta (Aβ) and hyperphosphorylated tau (pTau) pathology in post-mortem human brain tissue from individuals with Alzheimer's disease (AD). We identified transcriptomic signatures associated with proximity to Aβ in the human inferior temporal cortex during late-stage AD, which we further investigated at cellular resolution with combined IF and single-molecule fluorescent in situ hybridization (smFISH). The study provides a data analysis workflow for Visium-SPG, and the data represent a proof-of-principle for the power of multi-omic profiling in identifying changes in molecular dynamics that are spatially associated with pathology in the human brain. We provide the scientific community with web-based, interactive resources to access the datasets of the spatially resolved AD-related transcriptomes.
神经退行性疾病患者大脑中的神经病理病变被认为会触发扰乱局部微环境稳态的分子和细胞过程。在这里,我们应用10x Genomics Visium Spatial Proteogenomics (Visium- spg)平台,该平台将空间基因表达与免疫荧光(IF)蛋白联合检测相结合,以评估其量化阿尔茨海默病(AD)患者死后脑组织中淀粉样蛋白- β (Aβ)和过度磷酸化tau (pTau)病理的空间基因表达变化的能力。我们在晚期阿尔茨海默病的人类下颞叶皮层中发现了与Aβ接近相关的转录组特征,并利用IF和单分子荧光原位杂交(smFISH)在细胞分辨率上进一步研究了这些特征。该研究为Visium-SPG提供了一个数据分析工作流程,这些数据代表了多组学分析在识别与人类大脑病理在空间上相关的分子动力学变化方面的能力的原理证明。我们为科学界提供基于网络的交互式资源,以访问空间解析ad相关转录组的数据集。
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引用次数: 0
Tissue Spatial Omics Dissects Organoid Biomimicry 组织空间组学解剖类器官仿生学
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-10-01 DOI: 10.1089/genbio.2023.0039
Nicholas Zhang, Denis Ohlstrom, Sicheng Pang, Nivik Sanjay Bharadwaj, Aaron Qu, Hans Grossniklaus, Ahmet F. Coskun
Recently, organoids, or three-dimensional (3D) cellular assemblies, have demonstrated promise as viable models for organ development and disease study. In contrast to challenging preclinical models, organoids are advantageous due to rapid fabrication times and greater patient specificity. The advent of spatial transcriptomics and single cell technologies has also enhanced the characterization of intraorganoid heterogeneity, thus highlighting 3D cell signaling and organ development at micro scales. In this study, we describe ongoing and future directions in spatial omics integrated with various imaging technologies for two-dimensional/3D organoid characterization. Utilizing both retinal organoids and native retinal tissues, we undertook an analysis to deconstruct the cellular compositions and structural attributes of their respective cell layers. Our findings indicate that the spatial organization of cell phenotypes is similar between organoids and native retinal tissue. However, it is noteworthy that native retinal tissue possesses thinner yet distinctly separated cell layers compared with the organoids.
最近,类器官或三维(3D)细胞组件已被证明有望作为器官发育和疾病研究的可行模型。与具有挑战性的临床前模型相比,类器官由于制造时间短和更大的患者特异性而具有优势。空间转录组学和单细胞技术的出现也增强了类器官内异质性的表征,从而在微观尺度上突出了三维细胞信号传导和器官发育。在这项研究中,我们描述了空间组学与各种二维/三维类器官表征成像技术相结合的当前和未来方向。利用视网膜类器官和天然视网膜组织,我们进行了分析,解构了它们各自细胞层的细胞组成和结构属性。我们的研究结果表明,细胞表型的空间组织在类器官和天然视网膜组织之间是相似的。然而,值得注意的是,与类器官相比,天然视网膜组织具有更薄但明显分离的细胞层。
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引用次数: 0
Spatial Delivery 空间交付
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-10-01 DOI: 10.1089/genbio.2023.29117.editorial
Rong Fan, Fay Lin
GEN BiotechnologyVol. 2, No. 5 Guest Editorial: Spatial OmicsFree AccessSpatial DeliveryRong Fan and Fay LinRong Fan*Address correspondence to: Rong Fan E-mail Address: [email protected]Department of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.Guest Editor, GEN Biotechnology.Search for more papers by this author and Fay Lin*Address correspondence to: Fay Lin E-mail Address: [email protected]Senior Editor, GEN Biotechnology.Search for more papers by this authorPublished Online:16 Oct 2023https://doi.org/10.1089/genbio.2023.29117.editorialAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Spatial omics enables the profiling of a variety of biomolecules with high spatial resolution across the central dogma of molecular biology directly in the natural tissue context. It has emerged as a powerful tool to analyze clinical samples for human biology research, therapeutic discovery, and translational medicine. As one of the fastest growing areas in the biotech industry, spatial omics is poised to drive the next biology revolution with broad impact across life science and medicine.In this debut special issue of GEN Biotechnology, we are delighted to feature a collection of spatial omics perspectives, reviews, and original research articles capturing the breadth of the field from cancer research to the newest advances in imaging methods.Lift OffThe historical roots of visualizing biological function date back 300 years with the invention of the compound microscope by Robert Hooke. Individual cells were seen for the first time in a plant leaf, and researchers could already visualize highly heterogeneous cell morphology implicated in distinct functions in various tissue regions. While the modern era of molecular and cell biology associates morphological heterogeneity with differential gene expression, it was the rise of single-cell genomewide gene expression measured by next-generation sequencing (NGS) platforms that allowed for detailed quantification of cellular heterogeneity in gene expression. Further breakthroughs in massively parallel single-cell sequencing via cellular barcoding enabled the gene expression profiling of thousands of single cells, thereby dissecting cell types and states in large cell populations. But despite these major breakthroughs in single-cell omics, analyzing cellular heterogeneity in the tissue context remained a challenge.Over the past decade, we have witnessed the exponential growth of an emerging field—spatial omics. The goal is to map genomewide biomolecular information pixel-by-pixel in undissociated tissue to yield a holistic view of cell type, state, and function in the native tissue context. Broadly speaking, there are two avenues to achieve this goal—one based on imaging, and the other based on NGS.Imaging-based spatial omicsAlthough single-molecule imaging and fluorescence
创BiotechnologyVol。2、第5期客座编辑:Spatial OmicsFree AccessSpatial delivery范荣、林菲范荣*通讯地址:范荣E-mail Address: [email protected]美国康涅狄格州纽黑文耶鲁大学生物医学工程系。GEN生物技术客座编辑。*通讯地址:Fay Lin E-mail Address: [email protected] GEN Biotechnology高级编辑。搜索本文作者的更多论文发表在线:2023年10月16日https://doi.org/10.1089/genbio.2023.29117.editorialAboutSectionsPDF/EPUB权限和引文spermissionsdownload引文strack引文添加到收藏返回出版物共享分享在facebook上推特链接InRedditEmail空间组学使各种生物分子的分析具有高空间分辨率跨越分子生物学的中心法则直接在自然组织的背景下。它已成为分析人类生物学研究、治疗发现和转化医学的临床样本的强大工具。空间组学是生物技术产业中发展最快的领域之一,它将在生命科学和医学领域产生广泛的影响,推动下一次生物学革命。在《GEN生物技术》的首期特刊中,我们很高兴为您呈现一系列空间组学的观点、评论和原创研究文章,这些文章涵盖了从癌症研究到成像方法的最新进展的广泛领域。可视化生物功能的历史根源可以追溯到300年前罗伯特·胡克发明的复合显微镜。单个细胞首次在植物叶片中被观察到,研究人员已经可以看到在不同组织区域中涉及不同功能的高度异质的细胞形态。虽然分子和细胞生物学的现代时代将形态异质性与差异基因表达联系起来,但通过下一代测序(NGS)平台测量单细胞全基因组基因表达的兴起,允许详细量化基因表达的细胞异质性。通过细胞条形码技术在大规模平行单细胞测序方面的进一步突破,使数千个单细胞的基因表达谱得以实现,从而在大细胞群体中剖析细胞类型和状态。但是,尽管单细胞组学取得了这些重大突破,但在组织背景下分析细胞异质性仍然是一个挑战。在过去的十年中,我们见证了空间组学这一新兴领域的指数级增长。目标是在未解离组织中逐像素绘制全基因组生物分子信息,以产生细胞类型,状态和功能在天然组织背景下的整体视图。一般来说,实现这一目标有两种途径,一种是基于成像,另一种是基于NGS。基于成像的空间组学虽然单分子成像和荧光原位杂交(FISH)是成熟的技术,但如何将它们扩展到全基因组表达成像还不是很直观。结合FISH探针是概念上的突破,正如多重误差-鲁棒性荧光原位杂交(MERFISH)和序列FISH所证明的那样,重复杂交和成像最终导致单分子FISH全基因组空间基因表达谱。单细胞分辨率的空间表型分析已成为分析肿瘤和肿瘤微环境(TME)的重要手段。虽然大多数高复杂性空间研究都集中在转录组学分析上(见第384页的评论文章),但Akoya Biosciences的研究人员提出了一个单细胞蛋白质空间分析框架,用于分析头颈部鳞状细胞癌,这是第七大常见癌症(见第419页)。作者指出,这种蛋白质组在体内平衡和疾病中的空间定位为识别新的生物标志物、疾病分层和理解可变临床反应的基础提供了应用。(有关空间组学和TME最新进展的更多新闻报道,请参阅Sachin Rawat在第342页的新闻特写。)Joakim Lundeberg及其同事于2016年发表在《科学》杂志上的一篇具有里程碑意义的论文展示了使用DNA微阵列(斑点大小为100 μm)来捕获从组织切片中释放的mRNA分子,该组织切片被放置在载片上并经渗透使mRNA分子逃逸。然后,载玻片上的逆转录生成空间条形码cDNA,可以使用配对端NGS进行汇总、扩增和分析,以逐点读取组织切片中空间分辨的无偏倚全基因组基因表达。该技术于2019年被10 ×基因组公司商业化,成为Visium空间平台,在各种生物和生物医学领域得到了迅速而广泛的应用。 这期的封面由才华横溢的艺术家monoo Yee精心设计,以研究最多的人体器官之一-大脑为特色,并说明空间组学如何为了解阿尔茨海默病(AD)等神经退行性疾病提供了强大的工具。在第399页,来自约翰霍普金斯大学的研究人员提出了一个路线图,用于识别AD患者死后脑组织中与淀粉样蛋白病理相关的空间分解转录特征。作者指出,他们的数据分析工作流程,使用10 × Visium空间蛋白质基因组学平台,代表了多组学分析在与脑病理相关的分子动力学空间表征中的力量的原理证明。在过去的三年中,用于空间转录组学分析的条形码固相RNA捕获的一般基础方法已经进一步改进,以展示亚细胞空间基因表达定位(例如,SeqScope, Stereo-seq和Pixel-seq)。尽管如此,它们都遵循伦德伯格提出的“用于mRNA捕获和空间转录组学的条形码固体表面”的基本原则。自2019年以来,出现了一种技术上截然不同的空间组学方法,一种基于空间定义的DNA条形码递送到固定和渗透组织中,在组织中执行确定性条形码以进行空间组学测序(DBiT-seq)。该方法具有高度的通用性,不仅首次展示了空间多组学测序(转录组和蛋白质),而且还进一步发展为空间分辨表观基因组测序(即空间- atac -seq和空间- cut&tag)以及空间表观基因组-转录组共测序。这在空间生物学领域开辟了一个全新的领域。鉴于基因表达谱在确定细胞类型或状态方面的重要作用,空间转录组学在很大程度上与空间基因表达图谱同义。但在空间基因表达之外出现的东西代表了这一领域最令人兴奋的前沿。如上所述,DBiT具有独特的多功能性,为空间表观基因组学开辟了一个全新的方向。最近,MERFISH等基于图像的方法也证明了与特定组蛋白标记相关的表观遗传位点的靶向检测。空间代谢组学是另一个分支,它准备提供与饮食、衰老和疾病有关的细胞功能的不可或缺的信息。质谱成像允许以无偏倚的方式对代谢物(如脂质组)进行近单细胞分辨率分析,以区分不同的脂质种类。包括红外和受激拉曼散射(SRS)成像在内的光学化学成像的独特之处在于,它可以以前所未有的亚细胞甚至纳米尺度的分辨率检测选定的代谢物,而且它是无损的和无标签的。在435页上,杜克大学的研究人员提出了一种无标签反射模式高光谱光声显微镜(RHS-PAM)系统,以克服传统高光谱成像方法的局限性,传统高光谱成像方法主要依赖于荧光特征,限制了它们在非荧光样品中的应用。该报告说明了RHS-PAM在一系列模式生物(包括秀丽隐杆线虫、斑马鱼和小鼠)中利用核酸、蛋白质、血红蛋白、黑色素和脂质的光学吸收对比的能力。RHS-PAM可以为临床医生提供一种更无创的方法来获得细胞水平的空间组学,从而为诊断和治疗打开新的大门。回到RNA分子的空间作图,一个RNA分子的生命是丰富而动态的,远远超出了空间基因表达所能揭示的能力。因此,研究人员仍在努力研究如何绘制RNA分子在其生命周期的不同阶段,它们的剪接变异,它们与蛋白质的相互作用,以及非编码RNA的调节机制——这些都是细胞和组织生物学中的重要问题。最后,我们想知道如何绘制生物分子和细胞的时间动态,以及如何在基因组尺度上绘制大型3D组织结构。这些是空间组学的下一个前沿领域,可能在未来几年出现。关
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引用次数: 0
Kallyope Is Digesting Gut–Brain Biology into Medicines Kallyope正在将肠道-大脑生物学转化为药物
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-10-01 DOI: 10.1089/genbio.2023.29116.jgr
Jonathan D. Grinstein
GEN BiotechnologyVol. 2, No. 5 News FeaturesFree AccessKallyope Is Digesting Gut–Brain Biology into MedicinesJonathan D. GrinsteinJonathan D. GrinsteinE-mail Address: [email protected]Senior Editor, GEN Media Group.Search for more papers by this authorPublished Online:16 Oct 2023https://doi.org/10.1089/genbio.2023.29116.jgrAboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail Founded by Columbia University stalwarts Charles Zuker, Richard Axel, and Tom Maniatis, the New York City company is advancing a portfolio of oral small-molecule therapies across metabolism, gastrointestinal disease, and neurological disorders.Charles Zuker, Professor of Biochemistry & Molecular Biophysics and a Professor of Neuroscience at Columbia UniversityCharles Zuker had been studying taste for decades when his lab performed an experiment knocking out the receptor for sweetness in mice to test whether it would be able to distinguish sugar water from plain old water.At first, the mice lacking sweet receptors drink equal amounts of each type of water, whereas a wild-type mouse soon figures out that one of the two is sugar-laden and consequently favor the sweet one. But return 2 days later, the mice are drinking exclusively from the sugar-rich water, even if they lack the receptor for sweetness.1“We figured that there has to be some post-ingestive effect that's triggering this preference. We discovered that this maniacal desire to consume sugar—not sweet, but sugar in particular—was driven by the activation of the gut-brain circuit,” said Zuker when describing the discovery that was the basis for his a-ha moment.“That led to the idea that, my goodness, if activating the circuit can so dramatically transform an animal's behavior, then maybe accessing the gut-brain circuit could also be used to change physiology, metabolism, and so forth,” said Zuker, who is a Professor of Biochemistry and Molecular Biophysics and a Professor of Neuroscience at Columbia University and a Howard Hughes Medical Institute Investigator (Box 1).Box 1. The gut–brain axis: a critical conduit for neural signals informing the brain of the body's metabolic and physiologic stateSurvival requires the integration of external information from senses such as sight, smell, sound, touch, and taste as well as internal sensory cues from the digestive tract.2 To guarantee proper regulation of body physiological processes and behaviors and to promote overall health, informational elements, such as ingested food, energy homeostasis, inflammatory signals, and digestive progress, need to be monitored from the gut.3 The intricate network of neural, sympathetic, endocrine, immune, humoral, and gut microbiota connections—also known as the “brain–gut axis”—controls gastrointestinal homeostasis and connects the brain's emotional and cognitive centers to the gut's functions. This network enables two-wa
创BiotechnologyVol。2、5号新闻特稿免费访问kallyope正在将肠道-大脑生物学转化为医学乔纳森·d·格林斯坦乔纳森·d·格林斯坦电子邮件地址:[email protected] GEN传媒集团高级编辑。搜索本文作者的更多论文出版在线:2023年10月16日https://doi.org/10.1089/genbio.2023.29116.jgrAboutSectionsPDF/EPUB权限和引文目录下载引文目录添加收藏返回出版分享分享在facebook上推特链接在redditemail这家位于纽约的公司由哥伦比亚大学的忠实支持者Charles Zuker, Richard Axel和Tom Maniatis创立,正在推进一种跨代谢的口服小分子疗法组合。胃肠道疾病和神经系统疾病查尔斯·祖克,哥伦比亚大学生物化学和分子生物物理学教授,神经科学教授查尔斯·祖克几十年来一直在研究味觉,他的实验室进行了一项实验,敲除了老鼠的甜味受体,以测试它是否能够区分糖水和普通的老水。起初,缺乏甜味受体的老鼠会喝等量的两种水,而野生型老鼠很快就能分辨出其中一种是含糖的,因此更喜欢甜味的那一种。但两天后,即使小鼠缺乏甜味感受器,它们也只喝富含糖的水。“我们认为一定有一些摄取后的影响触发了这种偏好。我们发现,这种疯狂的吃糖的欲望——不是甜的,尤其是糖——是由肠道-大脑回路的激活驱动的,”祖克在描述这一发现时说,这是他顿悟时刻的基础。祖克是哥伦比亚大学生物化学和分子生物物理学教授、神经科学教授、霍华德休斯医学研究所研究员,他说:“这导致了这样一个想法,我的天哪,如果激活这个回路可以如此戏剧性地改变动物的行为,那么进入肠脑回路也可以用来改变生理、新陈代谢等等。”肠脑轴:神经信号向大脑传递身体代谢和生理状态的关键通道。生存需要整合来自视觉、嗅觉、听觉、触觉和味觉等感官的外部信息,以及来自消化道的内部感官信号为了保证身体生理过程和行为的适当调节,促进整体健康,需要从肠道监测信息元素,如摄入的食物、能量稳态、炎症信号和消化过程神经、交感神经、内分泌、免疫、体液和肠道微生物群连接的复杂网络——也被称为“脑肠轴”——控制胃肠道稳态,并将大脑的情感和认知中心与肠道功能联系起来。这个网络使大脑和胃肠道之间的双向通信成为可能,胃肠道是5亿个神经元、100多万亿个微生物和大多数人体免疫细胞的家园脑肠轴作为胃肠道和精神疾病(如炎症性肠病(IBD),抑郁症,6和创伤后应激障碍)的治疗靶点正变得越来越重要。排列在胃肠道上的被称为肠内分泌细胞的特殊上皮细胞总是监测食物的内容物,胃肠道壁内的感觉神经末梢、肠神经元和肠内分泌细胞检测与摄入和消化有关的机械变化半自主的肠神经系统有时被称为“第二大脑”,具有多种作用,包括胃肠道的运动,改变局部血液流动,修改营养处理,并与肠道的免疫和内分泌系统相互作用。9,10有趣的是,在早期的研究中,人们注意到许多神经系统疾病与人类患者的消化问题之间存在明确的联系,并广泛证明了这一点,11表明肠-脑轴不仅对食欲控制和肠道免疫很重要,而且对大脑认知功能也很重要。迷走神经是连接胃肠系统和中枢神经系统的重要神经中枢,是脑肠轴的重要组成部分,在能量平衡、食物摄入、体液平衡、消化、免疫反应、奖赏、记忆和认知等多种功能中起着重要作用迷走神经还在营养和精神疾病(包括情绪和焦虑症)以及炎症性疾病(如炎症性肠病)之间起着重要的联系作用。 通过肠道进入大脑是革命性的,因为它可以绕过一些最大的挑战,如脱靶效应、大脑可达性和血脑屏障。更重要的是,这种药理操作可以系统地影响人体生物学,改变生理和代谢。但是了解肠脑轴——肠道和大脑之间的双向交流——提供的不仅仅是与大脑的直接联系。它还为大脑、肠道和身体之间的交流提供了接入点,这可以影响各种硬连线的系统电路。这些概念导致Zuker发现了Kallyope,智利神经遗传学家通过瞄准肠-脑轴的自然回路来改变药物范例。“当我们想到药物发现时,我们通常会想到分子、蛋白质或受体,”Zuker说。“这些都是至关重要的参与者,但我们试图改变的是自然回路发出信号的方式,这大大拓宽了我们找到合适目标的方式,因为现在我们必须调整的不是这个有缺陷的蛋白质或这个分子。”我们的目标是:我们能否改变交流的方式,让大脑做出适当的调整?这是一个非凡的机会,通过简单地利用自然生物学来改变身体生理、新陈代谢、免疫和器官功能,而不必真的把一个分子送入大脑。”2015年,在Lux Capital的支持下,Zuker找到了他在哥伦比亚大学的“两位最亲密的朋友和同事”,诺贝尔奖得主Richard Axel和著名分子生物学家Tom Maniatis,以这个以肠脑轴为平台的前提下,形成了Kallyope。迄今为止,kallyope(在希腊语中意味着美丽的声音,也是希腊史诗和口才女神的名字)已经筹集了近4.8亿美元,包括2020年3月的1.12亿美元C轮融资和2022年2月的2.36亿美元D轮融资,并在诊所有两个牵头项目。大约在祖克推出Kallyope的时候,南希·索恩伯里(Nancy Thornberry)离开了她在默克公司的长期职位,在那里她是糖尿病和内分泌学研究的负责人。她并不一定要找一个手术方面的工作,但祖克利用肠脑轴来治疗未满足需求的疾病区域(包括各种神经系统疾病)的概念吸引了她。索恩伯里是Kallyope的创始首席执行官兼研发主席。反过来,Thornberry从默克公司吸引了一批人才,包括现任首席执行官兼总裁Jay Galeota,他在默克公司工作了28年,以及Ann Weber,她为40多个开发候选药物做出了贡献,包括治疗2型糖尿病(T2D)的JANUVIA(西格列汀)。在他们的监督下,Kallyope正在利用许多在系统神经科学研究中出现的先进技术,对肠-脑轴基础的神经和激素回路进行更全面的分子理解,并确定新的治疗方法。这个平台被称为Klarity。Kallyope平台的核心技术之一是单细胞测序,这是该公司2015年成立时的一项新技术。Thornberry说,在过去的8年里,Kallyope对小鼠和人类肠道-脑轴的每个主要组成部分的每种特化细胞类型都有了全面的了解,包括肠道上皮、肠神经系统和免疫细胞。“这是一次非常英勇的努力,我们可能是唯一拥有这些全面地图集的人,”索恩伯里说。“这让你开始思考这些特殊的细胞类型是做什么的,以及它们是如何在一个回路中工作来调节生理的。”Kallyope还利用电路映射技术,如光遗传学、化学遗传学、解剖追踪和计算映射来描绘神经回路的功能。Kallyope平台的另一个关键部分是肠道类器官,这在公司成立时也是一项新技术,这促使汉斯·克莱弗斯(Hans Clevers)加入了科学顾问委员会。索恩伯里说,他们已经能够创建一个可能是肠道类器官行业领先的平台,来观察激素分泌和肠道屏障功能。他说:“Kallyope取得的成就是取得了基本的、基本的发现,这些发现广泛地定义了身体和大脑之间的整个通信线路,并将它们分解成基本的组成部分,以一种他们现在可以探测或排列的方式,我认为这是非常令人兴奋的。”治疗管道在Klarity平台的背后,Kallyope已经建立了两个临床试验项目的投资组合,还有几个项目即将进行。
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引用次数: 0
Developing Treatments for Rare Diseases on a Shoestring 小成本开发罕见疾病的治疗方法
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-10-01 DOI: 10.1089/genbio.2023.0033
Ana C. Puhl, Sarah Negri, Maggie A.Z. Hupcey, Sean Ekins
There are thousands of rare genetic diseases lacking an approved treatment, many of which are life limiting to children. Those caused by a missing protein may represent a target for protein replacement either by enzyme replacement therapy or by gene therapy. One of the many challenges working on these types of genetic diseases is the availability of funding, as these diseases typically affect very small number of patients. Here we offer a novel case study of our approach to developing a treatment for one such rare disease, which has not required venture capital, angel investment, or funding by foundations to date. We have instead pursued NIH small business grants to fund the early preclinical work performed by our academic collaborators and ourselves. Our approach to developing a treatment for a rare disease on a shoestring budget is unlike any of the alternative approaches to funding.
有数千种罕见的遗传疾病缺乏经批准的治疗方法,其中许多是儿童的生命限制。那些由缺失蛋白质引起的疾病可能是通过酶替代疗法或基因疗法替代蛋白质的目标。研究这类遗传病的诸多挑战之一是资金的可得性,因为这些疾病通常只影响极少数患者。在这里,我们提供了一个新的案例研究,说明我们开发一种治疗这种罕见疾病的方法,迄今为止,这种方法不需要风险资本、天使投资或基金会的资助。我们转而寻求NIH的小企业资助,以资助我们的学术合作者和我们自己进行的早期临床前工作。我们以有限的预算开发一种罕见疾病的治疗方法,与其他任何筹资方法都不同。
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引用次数: 0
From Ultraviolet to Near-Infrared: Label-Free Reflection-Mode Hyperspectral Photoacoustic Microscopy for Single-Cell Biochemical Mapping 从紫外到近红外:用于单细胞生化制图的无标签反射模式高光谱光声显微镜
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-10-01 DOI: 10.1089/genbio.2023.0035
Qiangzhou Rong, Carlos Taboada, Ángela del Águila, Ilaria Merutka, Nishad Jayasundara, Yushun Zeng, Wei Yang, Qifa Zhou, Junjie Yao
Hyperspectral imaging has emerged as a valuable technique for analyzing biological tissue compositions by probing intrinsic or exogenous biomolecules. However, conventional hyperspectral imaging methods predominantly rely on fluorescent signatures, limiting their application to nonfluorescent samples. To overcome this limitation, a label-free reflection-mode hyperspectral photoacoustic microscopy (RHS-PAM) system has been developed. RHS-PAM enables the imaging of thick biological samples with a wide range of intrinsic contrasts using excitation wavelengths ranging from ultraviolet to near infrared. RHS-PAM eliminates the need for tissue staining, and has achieved cellular-level spatial resolution and automatic image coregistrations at all wavelengths. Proof-of-concept applications of RHS-PAM have been demonstrated on various model organisms, including Caenorhabditis elegans, frog tadpole, zebrafish, and mouse. The technique has successfully imaged a wealth of structural and molecular features in these organisms, utilizing the optical absorption contrast of nucleic acids, proteins, hemoglobin, melanin, and lipids. The results highlight the capability of RHS-PAM to provide rich optical contrast, high spatial resolution, and an extended spectral range for label-free imaging. We believe that RHS-PAM represents a highly promising tool for single-cell biochemical mapping of diverse biological tissues.
高光谱成像已成为一种有价值的技术,用于分析生物组织组成的探测内在或外源的生物分子。然而,传统的高光谱成像方法主要依赖于荧光特征,限制了它们在非荧光样品中的应用。为了克服这一限制,开发了一种无标记反射模式高光谱光声显微镜(RHS-PAM)系统。RHS-PAM能够使用从紫外到近红外的激发波长对具有宽范围内禀对比度的厚生物样品进行成像。RHS-PAM消除了对组织染色的需要,并在所有波长下实现了细胞级空间分辨率和自动图像共配准。RHS-PAM的概念验证应用已经在多种模式生物上得到证实,包括秀丽隐杆线虫、青蛙蝌蚪、斑马鱼和小鼠。该技术利用核酸、蛋白质、血红蛋白、黑色素和脂质的光学吸收对比,成功地对这些生物的丰富结构和分子特征进行了成像。结果表明,RHS-PAM能够提供丰富的光学对比度、高空间分辨率和扩展的无标签成像光谱范围。我们相信RHS-PAM是一种非常有前途的工具,可以用于多种生物组织的单细胞生化制图。
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引用次数: 0
23andMe Therapeutics: From Genes to Drugs 23andMe Therapeutics:从基因到药物
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-08-01 DOI: 10.1089/genbio.2023.29109.jle
Julianna LeMieux
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引用次数: 0
Deciphering the Evolutionary Adaptations of Life with a Minimal Genome 用最小基因组解读生命的进化适应
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-08-01 DOI: 10.1089/genbio.2023.29108.fme
Fankang Meng, T. Ellis
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引用次数: 0
Are Microbiome Therapeutics Finally Here? 微生物组疗法终于来了吗?
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-08-01 DOI: 10.1089/genbio.2023.29105.mki
Matthew Kirshner
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引用次数: 0
Taste the Sun: Gene Editing Produces Vitamin D-Enhanced Tomatoes 品尝阳光:基因编辑生产维生素d增强的西红柿
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2023-08-01 DOI: 10.1089/genbio.2023.29107.fli
Fay Lin
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引用次数: 0
期刊
GEN biotechnology
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