1st year MSc (Interdisciplinary Biomedical Research). The student will be assigned to a PhD project prior to the 2nd year of study.
1st year MSc (Interdisciplinary Biomedical Research). The student will be assigned to a PhD project prior to the 2nd year of study.
批准号:
2714864
负责人:
金额:
$0.0万
依托单位:
依托单位国家:
英国
项目类别:
Studentship
财政年份:
2022
资助国家:
英国
项目状态:
未结题
起止时间:
2022 至 --
中文摘要
细菌对抗生素的耐药性是对人类健康的威胁。缺乏有效的抗生素是一种直接威胁,其形式是无法治愈限制生命或危及生命的感染,同时也是一种对健康的间接威胁,因为没有抗生素,我们就无法进行使患者感染风险增加的医疗治疗(例如手术、移植、化疗)。如果我们能够更好地了解细菌种群如何进化出对抗生素的耐药性——涉及哪些基因突变,耐药性产生的速度有多快,耐药性是否对细菌对其他药物的敏感性有任何连锁反应——我们将更好地有效使用抗生素——即选择正确的药物和正确的治疗模式(开多少药,多久一次),这样细菌就更难产生耐药性。为了了解耐药性的进化,科学家们在抗生素存在的情况下进行了几代细菌培养实验,以观察细菌数量的变化。这些实验大多是在标准的实验室培养基中进行的,这些培养基是为了让细菌快速生长而设计的,而不是为了模仿致病菌生长的体内环境。这是一个问题。不同感染部位的不同环境,如营养物质的可用性、氧气的可用性和宿主免疫系统施加的压力,都可能影响耐药性进化的容易程度、自然选择的突变以及耐药性如何改变细菌的生理机能。在这个项目中,我将研究可以感染多个身体部位的细菌(铜绿假单胞菌和大肠杆菌)如何在模拟呼吸道、泌尿道或伤口感染的条件下进化出抗生素耐药性。我的工作将有助于改进现有抗生素的使用策略,并提供测试细菌对新型抗生素产生耐药性的容易程度的方法。
英文摘要
Bacterial resistance to antibiotics is a threat to human health. A lack of effective antibiotics poses a direct threat in the form of an inability to cure life-limiting or life-threatening infections, and also an indirect threat to health because without antibiotics, we could not carry out medical treatments that leave patients with an increased risk of infection (e.g. surgery, transplants, chemotherapy). If we can better understand how bacterial populations evolve resistance to antibiotics - what genetic mutations are involved, how fast resistance arises, whether resistance has any knock-on effects on bacterial susceptibility to other drugs - we will be better positioned to use antibiotics effectively - i.e. to choose the right drugs and the right treatment patterns (how much to prescribe, how often) so it is harder for the bacteria to become resistant. To understand resistance evolution, scientists carry out experiments culturing bacteria over many generations in the presence of antibiotics to see how the population changes. Most of these experiments are carried out in standard laboratory growth media, which are designed to allow bacteria to grow very rapidly rather than being designed to mimic the environments within the body where pathogenic bacteria grow. This is a problem. The different environments at distinct infection sites, such as nutrient availability, oxygen availability, and stress imposed by the host immune system, could all affect how easily resistance evolves, what mutations are naturally selected for, and how resistance changes bacterial physiology. In this project, I will study how bacteria that can infect multiple body sites (P. aeruginosa and E. coli) evolve antibiotic resistance in conditions that mimic infections of the respiratory, urinary tract or wounds. My work will help improve strategies the use of existing antibiotics, and provide ways to test how easily bacteria can evolve resistance to novel antibiotics.
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