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

抗菌清洁产品的广泛使用导致杀菌剂释放到环境中，这些杀菌剂生物降解性差，对水生生物有毒。为了满足对更环保、更有效的抗菌清洁剂的需求，本项目重点研究了广谱溶菌酶（lysins）的合理设计，并对其在家用清洁产品中的功效和稳定性进行了评价。溶酶素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，几乎所有生物都产生它们，如动物、植物、真菌、噬菌体和细菌本身，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菌素的例子。然而，大多数天然溶酶的目标细菌范围很窄，不适合用于清洁产品，因为它们的活性和稳定性会受到这些产品中常见成分的影响。这个博士项目的目标是设计一种针对多种细菌的新型溶酶，并可作为环保无毒的抗菌添加剂用于家用清洁剂。该项目不仅将产生关于这些新型溶酶素的分子结构、活性、特异性和抗菌功效的关键基础知识，而且将把这些基础知识与高影响力的工业应用相结合。这个博士项目提供了一个优秀的，多学科的培训机会，在微生物学，化学（肽科学）和生物物理学的界面。培训将在细菌细胞生物学中心（纽卡斯尔大学）和生物物理科学研究所和化学系（达勒姆大学）的优秀研究设施中提供，并将包括成功克隆，表达和设计不同溶酶所需的所有分子生物学技术，以及纯化这些新溶酶所需的生物化学技术，并评估其酶活性和溶菌效果。此外，将有机会利用固相肽合成技术制备抗菌肽。博士研究生就读于纽卡斯尔大学医学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方面的额外当地培训。

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.