MRC Centre for Genomics and Global Health

控制传染病的一个主要障碍是病原体和病媒在不断演变。流行病暴发是这一过程的一种表现。另一个后果是地方病逐渐向更难以控制的形式转变。对药物、疫苗和杀虫剂的抗药性日益增强，有可能破坏稳定，在某些情况下还可能破坏为减轻疟疾、结核病、艾滋病毒、肺炎球菌和其他地方病造成的发病率和死亡率负担而作出的国际努力。控制地方病的一个基本困境是，整个目的是通过一切可能的手段，包括大规模公共卫生干预，攻击已确定的病原体或病媒种群，但这一策略可能适得其反，因为它创造了一种新的进化格局，导致更强毒或更耐药的形式出现。有许多例子表明，控制工作在短时间内减轻了疾病负担，但最终导致耐药病原体菌株的出现和疾病以较不可控的形式卷土重来。病原体无法识别地理边界，因此世界各地的协作小组必须能够有效地建立、共享和分析大型复杂的数据集。这带来了几个挑战。通常缺乏整合研究同一疾病的实验室和实地研究地点数据的系统。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具备应对这一挑战所需技能的科学家。基因组监测的出发点是让世界各地的研究人员共同努力，确定全球人口中常见的变异形式。寄生虫和昆虫媒介具有庞大复杂的基因组，需要先进的测序技术和分析方法。该中心将发展统计和人口遗传方法来解决这些分析问题。需要进行能力建设，使资源贫乏国家的研究人员能够参与这一努力，并在这方面发挥领导作用。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。我们的翻译目标是提供基于网络的工具来帮助疾病控制项目。计划和监测其干预措施的进展。这需要以高空间分辨率和接近实时的方式捕捉病原体和媒介种群的变化。该中心将开发工具，使实地小组能够研究遗传微观流行病学。为了最大限度地发挥基因组变异和种群遗传数据的价值，它需要以一种可获取的格式与其他信息来源，如流行病学和生态数据相结合。该中心将制定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蔓延的不同因素的综合地图。该中心旨在成为传染病基因组监测和确定利用这些新技术改善全球健康的有效方法领域的国际卓越中心。

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.