Noisy Strep

摘要肺炎链球菌是在儿童和老年人和/或免疫受损的成人中引起侵袭性（肺炎、脑膜炎、菌血症）和非侵袭性（急性中耳炎、鼻窦炎）疾病的主要病原体。在过去的几十年里，具有多重抗生素耐药性的肺炎球菌菌株的出现和传播对人类健康构成了严重威胁。病原体发展的策略由所谓的双稳态调节，并且可能导致细菌的耐药形式（例如生物膜）的形成。转录噪声是转录调控系统转换的主要决定因素。因此，对S.肺炎是高度医学相关的。通过使用生物化学和微生物学的尖端技术以及数学建模，我们将解决S.肺炎这将导致高分辨率的系统水平的理解的作用，转录噪音在人类病原体的基因调控。这些结果将为智能药物设计提供新的目标，以操纵病原菌的分化和生命策略决策。

Summary. Streptococcus pneumoniae is a major pathogen causing invasive (pneumonia, meningitis, bacteraemia) and non-invasive (acute otitis media, sinusitis) disease in children and in elderly and/or immuno-compromised adults. The last decades have seen the emergence and spread of pneumococcal strains with multiple antibiotic resistance posing a serious threat to human health. The strategy of the pathogen development is regulated by so called bistability, and may lead to formation of drug resistant forms of bacteria, such as biofilms. Transcriptional noise is the main determinant of switching of bistable systems. Therefore, understanding of molecular mechanisms giving birth to the noise in transcription in S. pneumoniae is highly medically relevant. By using cutting-edge techniques in biochemistry and microbiology as well as mathematical modelling we will address the problem of origins of transcriptional noise in S. pneumonia. This will result in a high resolution systems-level understanding of the role of transcriptional noise in gene regulation of a human pathogen. The results will potentially provide a new target for intelligent drug design to manipulate differentiation and life-strategy decisions of pathogenic bacteria.