Newton001 Understanding Antimicrobial Resistance Mutations in Tuberculosis: Towards Personalised Treatment to Combat Multi-drug Resistance

Newton001 了解结核病中的抗菌素耐药性突变：迈向对抗多重耐药性的个性化治疗

• 批准号: MR/M026302/1
• 负责人: Sharon Peacock
• 金额: $ 6.29万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FM026302%2F1
• 关键词: Newton001; Understanding; Antimicrobial; Resistance; Mutations

Tuberculosis is recognised as one of Brazil's leading infectious diseases, with over 70,000 cases notified each year. There has been a significant increase in the number of diagnosed Multidrug resistant TB cases, with 10% of those also resistant to the two most important second---line class drugs (XDR-TB). This project aims to build upon existing collaborative programs on understanding effects of mutations, and on combating multidrug resistant and extensively drug resistant (MDR and XDR respectively) tuberculosis (TB). The two nodes, Brazil and UK, have complementary skills that encompass epidemiology, human and pathogen genetics, bioinformatics, structural biology and drug discovery. This multidisciplinary combination will facilitate the development of a novel platform to rapidly identify resistant TB from genomic sequencing. Novel mechanisms of drug resistance in TB will be explored using cutting edge techniques and correlated with clinical outcomes. This will help guide more suitable patient treatment, public health policies and future drug discovery efforts, with potential to bring benefit to individuals and public health in Brazil and UK, providing solutions to a problem that affects a third of the world's population.

结核病被认为是巴西的主要传染病之一，每年通报的病例超过70，000例。经诊断的耐多药结核病例数量显著增加，其中10%的病例对两种最重要的二线药物（广泛耐药结核）也有耐药性。该项目旨在建立在现有的合作计划上，了解突变的影响，并对抗多药耐药和广泛耐药（分别为MDR和XDR）结核病（TB）。巴西和英国这两个节点具有互补的技能，包括流行病学、人类和病原体遗传学、生物信息学、结构生物学和药物发现。这种多学科的结合将有助于开发一种新的平台，从基因组测序中快速识别耐药结核病。结核病耐药性的新机制将使用尖端技术进行探索，并与临床结果相关联。这将有助于指导更合适的患者治疗，公共卫生政策和未来的药物发现工作，有可能为巴西和英国的个人和公共卫生带来好处，为影响世界三分之一人口的问题提供解决方案。

项目成果

Nedd8 hydrolysis by UCH proteases in Plasmodium parasites

疟原虫寄生虫中 UCH 蛋白酶对 Nedd8 的水解

• DOI: 10.17863/cam.46680
• 发表时间: 2019
• 作者: Artavanis-Tsakonas K

Understanding and predicting the functional consequences of missense mutations in BRCA1 and BRCA2.

了解和预测 BRCA1 和 BRCA2 错义突变的功能后果。

• DOI: 10.17863/cam.85892
• 发表时间: 2022
• 作者: Aljarf R

pdCSM-cancer: Using Graph-Based Signatures to Identify Small Molecules with Anticancer Properties.

• DOI: 10.1021/acs.jcim.1c00168
• 发表时间: 2021-07-26
• 期刊: Journal of chemical information and modeling
• 影响因子: 5.6
• 作者: Al-Jarf R;de Sá AGC;Pires DEV;Ascher DB
• 通讯作者: Ascher DB

Combating mutations in genetic disease and drug resistance: understanding molecular mechanisms to guide drug design

对抗遗传疾病和耐药性的突变：了解指导药物设计的分子机制

• DOI: 10.17863/cam.12949
• 发表时间: 2017
• 作者: Albanaz A

mCSM-AB2: Guiding Rational Antibody Design Using Graph-Based Signatures

mCSM-AB2：使用基于图形的签名指导合理的抗体设计

• DOI: 10.17863/cam.44980
• 发表时间: 2020
• 作者: Ascher D