Biodesign and Engineering of Functionalized Spider Silk Variants

功能化蜘蛛丝变体的生物设计和工程

• 批准号: 2505676
• 金额: --
• 依托单位: University of Manchester
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2505676
• 关键词: Biodesign; Engineering; Functionalized; Spider; Silk

Spider silk is a high-performance biomaterial with exciting applications ranging from personal protective clothing to surface coatings for medical implants and guides for neuronal regeneration. Harvesting silk from spiders is tedious and economically not viable on a large scale. Consequently, the heterologous production of silk in a wide range of host organisms (from bacteria to goats) has been the focus of intense synthetic biology research. In this project, we intend to build on these advances to create libraries of functionalised spider silk derivatives for various applications.The work will include four closely interlinked work packages, which will interact through an iterative design - build - test - learn cycle in several rounds during the lifetime of the project.Design: The first part of the project will exploit recently available spider genome and transcriptome sequences to characterize the full spectrum of natural spider silk sequences. The aim is to identify design patterns of silk sequences that correlate with biophysical properties of the resulting silk.Build: The second part of the project will test the inferred design patterns, using DNA synthesis and automated DNA assembly pipelines to create diverse libraries of silk proteins, for expression and characterization. We will use Escherichia coli, as well as biotechnologically promising alternative bacterial host species, to produce and isolate the engineered silk proteins.Test: To facilitate the high-throughput materials testing of these libraries, a third part of the project will focus on the development of suitable tags for the expressed silks, which will allow rapid determination of expression levels and correlation with key biophysical properties of the resulting spun material. Spinning will be based on a range of dry- and wet-spinning approaches, and the resulting fibres will be tested using a collection of biophysical and materials science assays.Learn: The fourth part of the project uses machine learning methods to predict improved sequence designs, which will be tested in several iterations of the design cycle.This project provides comprehensive interdisciplinary training in methods pioneered by the supervisory team, across a range of key disciplines at the interface of biology and engineering, essential for the next generation of biotechnology scientists.

蜘蛛丝是一种高性能生物材料，其应用范围从个人防护服到医疗植入物的表面涂层和神经元再生指南。从蜘蛛身上收获丝是乏味的，并且在经济上不可行。因此，在广泛的宿主生物体（从细菌到山羊）中异源生产蚕丝一直是合成生物学研究的焦点。在这个项目中，我们打算在这些进展的基础上，创建用于各种应用的功能化蜘蛛丝衍生物库。这项工作将包括四个紧密相连的工作包，它们将在项目的生命周期中通过几轮迭代的设计-构建-测试-学习循环进行交互。设计：该项目的第一部分将利用最近可用的蜘蛛基因组和转录组序列来表征天然蜘蛛丝序列的全谱。构建：该项目的第二部分将测试推断出的设计模式，使用DNA合成和自动DNA组装管道来创建用于表达和表征的多种丝蛋白文库。我们将使用大肠杆菌，以及生物技术上有前途的替代细菌宿主物种，生产和分离工程丝蛋白。测试：为了促进这些文库的高通量材料测试，该项目的第三部分将集中于为表达的丝开发合适的标签，这将允许快速测定表达水平以及与所得纺制材料的关键生物物理性质的相关性。纺纱将基于一系列干纺和湿纺方法，所得纤维将使用一系列生物物理和材料科学分析进行测试。该项目的第四部分使用机器学习方法来预测改进的序列设计，这将在设计周期的几个迭代中进行测试。该项目提供了由监督团队开创的方法的全面跨学科培训，在生物学和工程学的接口，为下一代生物技术科学家必不可少的一系列关键学科。