Engineering of broad-spectrum chimeric antibacterial lysins for use in household cleaning products

抗微生物清洁产品的广泛使用导致生物杀灭剂释放到环境中，生物杀灭剂可生物降解性差并且对水生生物有毒。为了满足对更环保，但仍然有效的抗菌清洁剂的需求，该项目的重点是广谱溶菌酶（溶酶）的合理设计，以及它们在家用清洁产品中的功效和稳定性的评估。赖氨酸可以通过降解细菌细胞壁的基本成分来杀死细菌。它们在自然界中无处不在，几乎由所有生物体产生，如动物，植物，真菌，真菌和细菌本身，以对抗细菌的竞争对手或入侵者。溶菌酶和血清酰胺酶是我们自身免疫系统产生的溶素的例子。然而，大多数天然溶素的目标细菌谱很窄，不适合用于清洁产品，因为它们的活性和稳定性可能会受到这些产品中常见成分的影响。本博士项目的目标是设计针对广泛细菌的新型溶素，可用作家用清洁剂中的环保无毒抗菌添加剂。该项目不仅将产生这些新型溶素的分子结构，活性，特异性和抗菌功效的关键基础知识，而且将联合收割机与高影响力的工业应用相结合。这个博士项目提供了一个杰出的，多学科的培训机会，在微生物学，化学（肽科学）和生物物理学的接口。培训将在细菌细胞生物学中心的一流研究设施中进行（纽卡斯尔大学）和生物物理科学研究所及化学系（达勒姆大学），并将涵盖所有的分子生物学技术所需的成功克隆，表达和工程化不同的溶素，以及纯化这些新溶素和评价其酶活性和溶菌效力所需的生物化学技术。此外，使用固相肽合成制备抗微生物肽的机会将是可用的。博士生就读于纽卡斯尔大学医学院的博士培训课程，该课程在刺激的研究环境中提供科学和技术研究技能以及可转移技能的额外本地培训。

The extensive use of antimicrobial cleaning products results on the release into the environment of biocides that can be poorly biodegradable and toxic to aquatic life. To address the need for more environmentally friendly, but still effective, antimicrobial cleaners, this project focuses on the rational design of broad-spectrum bacteriolytic enzymes (lysins), and the evaluation of their efficacy and stability in household cleaning products. Lysins can kill bacteria by degrading essential components of the bacterial cell wall. They are ubiquitous in nature and produced by virtually all organisms such as animals, plants, fungi, phages, and bacteria themselves to fight bacterial competitors or invaders. Lysozyme and serum amidase are examples of lysins produced by our own immune system. However, most natural lysins have a narrow spectrum of target bacteria and are not suitable for use in cleaning products as their activity and stability can be impacted by the ingredients commonly present in these products.The objective of this PhD project is to engineer novel lysins that target a wide range of bacteria and can be used as eco-friendly and non-toxic antimicrobial additives in household cleaners. The project will not only generate key fundamental knowledge on the molecular architecture, activity, specificity, and antibacterial efficacy of these novel lysins but will combine this fundamental understanding with a high impact industrial application.This PhD project offers an outstanding, multidisciplinary training opportunity at the interface of microbiology, chemistry (peptide science) and biophysics. Training will be provided at the excellent research facilities of the Centre for Bacterial Cell Biology (Newcastle University) and the Biophysical Sciences Institute and Chemistry Department (Durham University) and will encompass all the molecular biology techniques required to successfully clone, express, and engineer different lysins, as well as the biochemistry techniques required to purify these new lysins and to evaluate their enzymatic activity and bacteriolytic efficacy. In addition, opportunities to prepare antimicrobial peptides using solid phase peptide synthesis will be available. The PhD student is enrolled at the doctoral training programme of the Faculty of Medical Sciences of Newcastle University which provides additional local training in scientific and technical research skills, and in transferable skills, within a stimulating research environment.