MATHEMATICAL MODELS OF H PYLORI GASTRIC COLONIZATION

描述(改编自申请人摘要)：幽门螺杆菌，a 定植于人胃的革兰氏阴性细菌与 上胃肠道疾病。选拔考试 幽门螺杆菌的压力为宿主与寄主菌群的相互作用提供了一个模型 由于(I)幽门螺杆菌菌株高度多样化，且持续变异是 发生在单一宿主的定植期间；(Ii)幽门螺杆菌菌株缺乏SOS 修复，天生有能力，并有很强的DNA交换能力 与其他幽门螺杆菌细胞合作，为观察到的 “准物种”发育；(Iii)幽门螺杆菌Lewis表达在 针对特定表型选择的定植和寄主特征； 已经确定了与Lewis变异有关的分子座位，并且 已经开发出了可以预测变异的小鼠模型 观察到；(V)建立了幽门螺杆菌定植的数学模型 总的来说，Lewis表达的动态可以被测量并发展成 模型来预测它的行为。具体目标是(1)构建一个 评估幽门螺杆菌种群遗传变化的实验啮齿动物模型 在单个宿主胃定植期间，并发展出一种确定性 具有代表性和预测性的数学模型。(2)评估 对原寄主表型、接种量、细菌突变的影响 幽门螺杆菌种群动态的宿主免疫应答， 表型，以及基因分型，以更好地识别参数的数学 模特。(3)考察两种不同的基因重组的效果。 幽门螺杆菌在实验感染过程中的菌株，并发展具有代表性的 这一更为复杂的现象的数学模型。

DESCRIPTION (Adapted from the Applicant's Abstract): Helicobacter pylori, a gram negative bacteria that colonize the human stomach, are associated with diseases of the upper gastrointestinal tract. Examination of the selective pressures on H.pylori provide a model for host interactions with resident flora since (I) H.pylori strains are highly diverse, and continued variation is occurring during colonization of a single host; (ii) H.pylori strains lack SOS repair, are naturally competent, and have substantial ability to exchange DNA with other H.pylori cells, providing opportunities for the observed "quasi-species" development; (iii) H.pylori Lewis expression varies during colonization and host characteristics selected for particular phenotypes; (iv) molecular loci have been identified that are involved in Lewis variation, and mouse models have been developed in which variation can be predictably observed; (v) Mathematical models have been developed for H.pylori colonization in general and the dynamics of Lewis expression can be measured and develop a model to predict its behavior. The specific aims are (1) To construct an experimental rodent model for assessing population genetic changes in H.pylori during gastric colonization of a single host, and to develop a deterministic mathematical model that is representative and predictive. (2) To assess the effects on variation of prior host phenotype, inoculum size, bacterial mutation rate, and host immunological response on H.pylori population dynamics, phenotypes, and genotypes to better identify the parameters of the mathematical model. (3) To examine the effect of recombination between two different H.pylori strains during experimental infections, and to develop representative mathematical models for this more complex phenomenon.