LEPROSY BACILLUS,: FROM GENOTYPE TO PHENOTYPE

描述（改编自申请人的摘要）：本申请的目的是 完全修改后的重新提交是确定和执行 用于麻风病诊断和流行病学监测的新抗原， 基于刚刚排序的连续M。麻风病的基因组， 独特的接触芽孢杆菌的途径， 流行病流行率下降和上升同时出现的流行病学难题 发病率。另一个假设驱动的推力是，一个有缺陷的基因型必须 反映在截短的表型中，其定义也将 提供知识和工具，以帮助解释麻风病的特点， 作为专性细胞内活动，特征性细胞向性和反应。S. 科尔（巴斯德研究所）将完成基因组的分析和注释 并生成数据库，为两个实验室的工作提供手段， （L 'Institut Pasteur; CSU）来定义转录组，多态性， 感染因子，和整个简化的蛋白质组通过克隆 靶向基因和体内表达蛋白质的完整阵列的定义。 CSU将应用分枝杆菌的基因组和结构知识， 定义简化的二级基因产物（LepLAM; LM;新的细胞外 脂质;肽聚糖等）。CSU，Fio-Cruz（C. Pessolani）和延世 大学（S.- N. Cho）将联合收割机在豚鼠身上测试新产品的DTH 反应，对麻风病人的PBMC的适当的T细胞 反应性，并针对血清进行抗体应答，以促进 新的皮肤抗原倡议，并提供新的血液分析， a t风险人群的诊断和识别。

DESCRIPTION (Adapted from the Applicant's Abstract): The purpose of this completely revamped resubmission is the identification and implementation of new antigens for the diagnosis and epidemiological monitoring of leprosy and is based on the just-sequenced contiguous M. leprae genome, on the investigators' singular access to the bacillus, and driven by the extraordinary epidemiological conundrum of a convergence of falling prevalence and rising incidence. The other hypothesis-driven thrust is that a defective genotype must be reflected in a truncated phenotype, the definition of which will also provide knowledge and tools to help explain the peculiarities of leprosy, such as obligate intracellularism, characteristic cell tropism and reactions. S. Cole (Institut Pasteur) will complete the analysis and annotation of the genome and generate databases to provide the means for a two-laboratory effort (L'Institut Pasteur; CSU) to define the transcriptome, polymorphism within the infectious agent, and the entire simplified proteome through cloning of targeted genes and definition of the full array of in vivo expressed proteins. CSU will apply the genome and the structural knowledge of mycobacteria to define the simplified secondary gene products (LepLAM; LM; new extracellular lipids; peptidoglycan; etc.). CSU, Fio-Cruz (C. Pessolani), and Yonsei University (S.-N. Cho) will combine to test new products in guinea pigs for DTH responses, against PBMC's of leprosy patients for appropriate T-cell reactivity, and against sera for antibody responses, with a view to advancing the new skin antigen initiative and providing new blood assays for early diagnosis and identification of a t risk populations.