MRC Centre for Genomics and Global Health

MRC 基因组学和全球健康中心

• 批准号: MR/M006212/1
• 负责人: Dominic Kwiatkowski
• 金额: $ 249.42万
• 依托单位: University of Oxford
• 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%2FM006212%2F1
• 关键词: MRC; Centre; Genomics; Global; Health

A major obstacle to the control of infectious disease is that pathogens and disease vectors are continually evolving. Epidemic disease outbreaks are one manifestation of this process. Another consequence is the progressive shift of endemic diseases towards forms that are more difficult to control. Increasing levels of resistance to drugs, vaccines and insecticides are threatening to destabilise and in some cases to ruin international efforts to reduce the burden of morbidity and mortality caused by malaria, tuberculosis, HIV, pneumococcus and other endemic diseases.A fundamental dilemma in controlling endemic disease is that the whole purpose is to attack an established pathogen or vector population by all means possible, including large-scale public health interventions, but this strategy may backfire by creating a new evolutionary landscape that causes more virulent or resistant forms to emerge. There are many examples of control efforts that have reduced disease burden for a short period of time but have eventually led to the emergence of resistant pathogen strains and the rebound of disease in a less controllable form. Pathogens do not recognise geographical boundaries, so it is essential that collaborating groups around the world can efficiently build, share and analyse large and complex datasets. This presents several challenges. Systems to integrate data across labs and field study sites working on the same disease are often lacking. Moreover, clinical and epidemiological researchers may lack the tools and training needed to make use of large-scale genome variation data, while genetics and genomics experts can lack the tools and data structures needed to make use of large-scale clinical and epidemiological data.There is an urgent need for scientists who appreciate the challenge and have the necessary skill set to tackle this challenge. The starting point for genomic surveillance is for researchers around the world to work together to identify common forms of variation in the global population. Parasites and insect vectors have large complex genomes that require advanced sequencing technologies and analytical methods. The Centre will develop statistical and population genetic methods to solve these analytical problems.Capacity building is needed to enable researchers in resource-poor countries to participate and to develop leadership in this effort. The Centre will help to build data-sharing networks to characterise global patterns of genome variation.Our translational goal is to provide web based tools to help disease control programmes.to plan and monitor the progress of their interventions. This requires changes in pathogen and vector populations to be captured at high spatial resolution and in near real time. The Centre will develop tools to enable groups in the field to do research on genetic micro-epidemiology.To maximise the value of genome variation and population genetic data it needs to be integrated with other sources of information, such as epidemiological and ecological data, in an accessible format. The Centre will develop methods for collecting data from multiple sources to construct integrated maps of the different factors that determine disease transmission and the spread of resistance. The Centre sets out to be an international centre of excellence in the field of genomic surveillance of infectious disease and identification of effective ways to use these new technologies to improve global health.

控制传染病的一个主要障碍是病原体和病媒不断进化。流行病的爆发就是这一过程的表现之一。另一个后果是地方病逐渐转向更难以控制的形式。对药物、疫苗和杀虫剂的耐药性不断增加，有可能破坏稳定，在某些情况下甚至会破坏国际社会为减轻疟疾、结核病、艾滋病毒、肺炎球菌和其他地方性疾病造成的发病率和死亡率负担而做出的努力。控制地方病的一个根本困境是，其全部目的是通过一切可能的手段，包括大规模公共卫生，攻击既定的病原体或病媒种群。 干预措施，但这种策略可能会适得其反，因为它会创造一个新的进化景观，导致更具毒性或抵抗力的形式出现。有许多控制努力在短时间内减轻疾病负担的例子，但最终导致耐药病原体菌株的出现以及疾病以较不可控的形式反弹。病原体无法识别地理边界，因此世界各地的合作团体必须能够有效地构建、共享和分析大型复杂的数据集。这带来了一些挑战。通常缺乏针对同一疾病跨实验室和现场研究地点整合数据的系统。此外，临床和流行病学研究人员可能缺乏利用大规模基因组变异数据所需的工具和培训，而遗传学和基因组学专家可能缺乏利用大规模临床和流行病学数据所需的工具和数据结构。迫切需要认识到这一挑战并拥有应对这一挑战所需技能的科学家。基因组监测的起点是世界各地的研究人员共同努力，以确定全球人口中常见的变异形式。寄生虫和昆虫载体具有庞大而复杂的基因组，需要先进的测序技术和分析方法。该中心将开发统计和人口遗传学方法来解决这些分析问题。需要进行能力建设，使资源匮乏国家的研究人员能够参与并在这项工作中发挥领导作用。该中心将帮助建立数据共享网络，以描述基因组变异的全球模式。我们的转化目标是提供基于网络的工具来帮助疾病控制计划。规划和监测其干预措施的进展。这需要以高空间分辨率且近乎实时地捕获病原体和媒介种群的变化。该中心将开发工具，使该领域的团体能够进行遗传微观流行病学研究。为了最大限度地发挥基因组变异和群体遗传数据的价值，它需要以可访问的格式与流行病学和生态数据等其他信息来源相整合。该中心将开发从多个来源收集数据的方法，以构建决定疾病传播和耐药性传播的不同因素的综合地图。该中心致力于成为传染病基因组监测领域的国际卓越中心，并确定使用这些新技术改善全球健康的有效方法。

项目成果

High-throughput genotyping assays for identification of glycophorin B deletion variants in population studies.

• DOI: 10.1177/1535370220968545
• 发表时间: 2021-04
• 期刊: Experimental biology and medicine (Maywood, N.J.)
• 作者: Amuzu DS;Rockett KA;Leffler EM;Ansah F;Amoako N;Morang'a CM;Hubbart C;Rowlands K;Jeffreys AE;Amenga-Etego LN;Kwiatkowski DP;Awandare GA
• 通讯作者: Awandare GA

Genome variation and population structure among 1142 mosquitoes of the African malaria vector species Anopheles gambiae and Anopheles coluzzii.

• DOI: 10.1101/gr.262790.120
• 发表时间: 2020-10
• 期刊: Genome research
• 影响因子: 7
• 作者: Anopheles gambiae 1000 Genomes Consortium

Interferon-gamma polymorphisms and risk of iron deficiency and anaemia in Gambian children.

冈比亚儿童的干扰素-γ多态性以及缺铁和贫血的风险。

• DOI: 10.12688/wellcomeopenres.15750.2
• 发表时间: 2020
• 期刊: Wellcome open research
• 作者: Abuga KM

Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia.

从冈比亚的颞和空间疟原虫对的基因组分析中选择的一致特征。

• DOI: 10.1038/s41598-018-28017-5
• 发表时间: 2018-06-26
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Amambua-Ngwa A;Jeffries D;Amato R;Worwui A;Karim M;Ceesay S;Nyang H;Nwakanma D;Okebe J;Kwiatkowski D;Conway DJ;D'Alessandro U
• 通讯作者: D'Alessandro U

Genetic markers associated with dihydroartemisinin-piperaquine failure in Plasmodium falciparum malaria in Cambodia: a genotype-phenotype association study.

与柬埔寨恶性疟原虫疟疾双氢青蒿素-哌喹失败相关的遗传标记：基因型-表型关联研究。

• DOI: 10.1016/s1473-3099(16)30409-1
• 发表时间: 2017-03
• 期刊: The Lancet. Infectious diseases
• 作者: Amato R;Lim P;Miotto O;Amaratunga C;Dek D;Pearson RD;Almagro-Garcia J;Neal AT;Sreng S;Suon S;Drury E;Jyothi D;Stalker J;Kwiatkowski DP;Fairhurst RM
• 通讯作者: Fairhurst RM