Developing Membrane Targeting Antimicrobial Lipo-Peptoids by Modular Peptidomimicry and High Throughput Imaging

通过模块化拟肽和高通量成像开发膜靶向抗菌脂肽

• 批准号: EP/X022889/1
• 负责人: Ruchika Goyal
• 金额: $ 26万
• 依托单位: University of Strathclyde
• 依托单位国家: 英国
• 项目类别: Fellowship
• 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=EP%2FX022889%2F1
• 关键词: Developing; Membrane; Targeting; Antimicrobial; Lipo

According to the World Health Organization, antimicrobial resistance (AMR) is one of the gravest threats to public health, causing already 33,000 lives lost in Europe p.a. and more globally, as well as lost productivity and increased healthcare costs. Developing new antimicrobials is an important tool for combating AMR, but discovering molecules with high selectivity for microbes (i.e. low toxicity for humans) is difficult. Moreover, typical biological assay and microscopy screening tools for identifying novel antimicrobials have a trade-off between screening efficiency and providing sufficient information to inform mechanistic understanding for driving innovation. In this project we aim to take advantage of a novel high speed, high resolution microscopy technique to fundamentally improve the quality and throughput of screening a new class of peptide-mimetic antimicrobials. In particular, preliminary results show that our "membrane targeting antimicrobial (lipo)peptoids" (mTAPs) should enable flexible modulation of antimicrobial activity and cell toxicity. Successful identification of a novel class of targeting antimicrobials and its subsequent development will be of great interest to both the pharmaceutical sector and to public health. The proposed methodology also has great potential to accelerate screening of other therapeutics. Both the methodological and therapeutics aspects will be substantive steps to the fight against AMR. Moreover, novel therapeutics and combating AMR are fully consistent with the UN's Sustainability Development Goal (SDG) 3 in Good Health and Wellbeing. The novel methodological approaches will also strengthening Europe's scientific infrastructure and the economy.

据世界卫生组织称，抗菌素耐药性 (AMR) 是对公众健康最严重的威胁之一，每年已导致欧洲 33,000 人丧生。在全球范围内，以及生产力下降和医疗保健成本增加。开发新的抗菌药物是对抗抗菌素耐药性的重要工具，但发现对微生物具有高选择性（即对人类低毒性）的分子很困难。此外，用于识别新型抗菌药物的典型生物测定和显微镜筛选工具在筛选效率和提供足够信息以促进创新的机制理解之间需要权衡。在这个项目中，我们的目标是利用一种新型的高速、高分辨率显微镜技术从根本上提高筛选新型肽模拟抗菌剂的质量和通量。特别是，初步结果表明，我们的“膜靶向抗菌（脂）类肽”（mTAP）应该能够灵活调节抗菌活性和细胞毒性。成功鉴定一类新型靶向抗菌药物及其后续开发将引起制药行业和公共卫生的极大兴趣。所提出的方法还具有加速其他疗法筛选的巨大潜力。方法论和治疗学方面都将是对抗抗菌药物耐药性的实质性步骤。此外，新型疗法和抗击抗菌素耐药性完全符合联合国可持续发展目标 (SDG) 3 的良好健康和福祉。新颖的方法论还将加强欧洲的科学基础设施和经济。