BBSRC-NSF/BIO - Deciphering the rules of nucleus architecture with synthetic cells and organelles

BBSRC-NSF/BIO - 用合成细胞和细胞器破译细胞核结构的规则

基本信息

批准号：
BB/W00125X/1
负责人：
Yuval Elani
金额：
$ 76.63万
依托单位：
Imperial College London
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2022
资助国家：
英国
起止时间：
2022 至无数据
项目状态：
未结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FW00125X%2F1
关键词：
BBSRC NSF BIO Deciphering rules

项目摘要

One of the hallmarks of cellular systems is the non-uniform spatial distribution of biomolecular content. Although compartmentalisation of content can be found across all life classes, it is a particularly marked feature in eukaryotes which contain a diverse array of subcellular organelles. Organelles are discrete structures within cells that exist in distinct chemical space, and are specialised to perform defined biochemical tasks. The dominant eukaryotic organelle is the nucleus which houses the genome and ensures spatial segregation of transcription and translation. It is thought that the ability of eukaryotes to compartmentalise functions in the nucleus and other organelles is behind their behavioural sophistication. Technological limitations, however, have meant that our fundamental understanding of the underpinning design principles that govern compartmentalisation in cells is lacking.Why do cells compartmentalise content? What defines the size and number of sub-compartments? How does nuclear architecture affect DNA transcription and protein synthesis? What governs the relationship between the size of the nucleus and the size of a cell? There is a need for new experimental and modelling technologies to shed light on these questions.Recent years have seen the emergence of bottom-up synthetic biology as a powerful new research discipline in the fundamental biosciences: re-engineering biology to decipher the rules of life by building synthetic cells. Synthetic cells are structures that mimic biological cells in form, function and behaviour. They are made by bringing together biomolecular blocks in defined combination to replicate aspects of cellular life: understanding biology by building a new biology. This research area has seen remarkable growth in recent times, partly driven by pioneering new technologies in our labs at Imperial and Caltech to model, manipulate and make new biomolecular systems.In this collaborative and international project, our UK and US teams will work in parallel to develop new microfluidic and synthetic biology technologies to assemble synthetic cells that contain nucleus-like organelles. Together with integration with new mathematical models, we will use our synthetic cells to investigate the above unresolved fundamental questions relating to cell biology. By deconstructing and reconstructing the key cellular architectural motif of the nucleus, we aim to unravel the fundamental principles of eukaryotic architecture, and of cellular compartmentalisation more generally. The modelling and experimental platforms we will be developing will be versatile, generalisable, open access, and deskilled, allowing our enabling technologies and toolkits to be utilised by the wider academic community to tackle diverse biological challenges using synthetic cells.Although this project will focus on questions relating to fundamental biology, the engineering rule-book we will be developing as a result of our insights, combined with the novel technologies we will be developing can be deployed for the construction of a new generation of synthetic cell devices with uses in the clinic and industry as smart therapeutic agents, as bioreactors, and in bioremediation. Moreover, the unique trans-Atlantic collaboration facilitated by this scheme will also serve as a bridge between large-scale consortia in the USA and UK dedicated to the grand challenge of building a synthetic cell from scratch.

细胞系统的标志之一是生物分子含量的非均匀空间分布。尽管可以在所有生命类别中找到内容的分区化，但在真核生物中，它是包含各种亚细胞细胞器的真核生物中特别明显的特征。细胞器是在不同化学空间中存在的细胞内的离散结构，并且专门执行定义的生化任务。主要的真核生物细胞器是容纳基因组并确保转录和翻译的空间分离的细胞核。人们认为，真核生物在细胞核和其他细胞器中隔离功能的能力是其行为成熟的背后。然而，技术局限性意味着我们对控制细胞中隔室化的基础设计原理的基本理解是缺乏的。为什么细胞会分隔含量含量？是什么定义了子街区的大小和数量？核结构如何影响DNA转录和蛋白质合成？是什么控制了细胞核大小与细胞大小之间的关系？需要新的实验和建模技术来阐明这些问题。订婚的年份已经将自下而上的合成生物学的出现视为基本生物科学中有力的新研究学科：重新工程生物学，通过构建合成细胞来破译生命规则。合成细胞是模仿形式，功能和行为的生物细胞的结构。它们是通过将生物分子块组合在一起的定义组合来复制细胞生活的各个方面来制作的：通过建立新的生物学理解生物学。该研究领域近来已经显着增长，部分是由我们在帝国和加州理工学院实验室开创的新技术驱动的，以模型，操纵和制造新的生物分子系统。在这个协作和国际项目中，我们的英国和美国团队将同时起作用，同时起开发新的微流体和合成生物学细胞，以组装成整体的构成细胞群。连同与新数学模型的集成在一起，我们将使用我们的合成细胞研究与细胞生物学有关的上述未解决的基本问题。通过解构和重建核的关键细胞结构基序，我们旨在揭示真核结构的基本原理和细胞分隔的基本原理。 The modelling and experimental platforms we will be developing will be versatile, generalisable, open access, and deskilled, allowing our enabling technologies and toolkits to be utilised by the wider academic community to tackle diverse biological challenges using synthetic cells.Although this project will focus on questions relating to fundamental biology, the engineering rule-book we will be developing as a result of our insights, combined with the novel technologies we will be developing can被部署用于构建新一代的合成细胞设备，并在诊所和工业中用作智能治疗剂，作为生物反应器和生物修复。此外，该计划促进的独特跨大西洋合作还将成为美国和英国大规模财团之间的桥梁，致力于从头开始建立合成细胞的巨大挑战。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Biomimetic behaviors in hydrogel artificial cells through embedded organelles.

DOI：
10.1073/pnas.2307772120
发表时间：
2023-08-29
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Allen, Matthew E.;Hindley, James W.;O'Toole, Nina;Cooke, Hannah S.;Contini, Claudia;Law, Robert, V;Ces, Oscar;Elani, Yuval
通讯作者：
Elani, Yuval

What it means to be alive: a synthetic cell perspective