Genetic studies in enteric bacteria

我实验室的工作目标是利用遗传学和基因组学的方法来揭示细菌种群中惊人程度的遗传变异的基础。沙门氏菌的2000多种血清型差别很大，包括在许多动物和人类中引起肠胃病的肠炎沙门氏菌血清型伤寒沙门氏菌，以及仅在人类中引起严重得多的伤寒沙门氏菌，以及数千种其他形式的沙门氏菌。我在20世纪60年代开始研究鼠伤寒沙门氏菌，当时我绘制了鼠伤寒沙门氏菌染色体的连锁图谱，图谱上不到200个基因；2001年，一个与其他实验室的合作项目对同一种细菌基因组中的4800个基因进行了测序。序列显示，在不同的血清型中存在称为岛的DNA片段，这些片段在一些血清型中存在，但在另一些血清型中缺失，这些片段产生不同的特性和毒性。伤寒有一个控制毒力抗原的岛；我们研究了那个岛的损失。在即将到来的奖助金期间，我们有两个主要目标。(1)肠道细菌的比较基因组分析。我们将完成与华盛顿大学基因组测序中心合作的7个基因组测序。我们参与了这七个基因组的基因注释，并对所有序列的基因组进行了总体比较，以揭示系统发育，并解释不同表型的基础。(2)研究噬菌体在细菌基因组中的存在及其作用。噬菌体存在于大多数基因组中，例如，鼠伤寒沙门氏菌菌株LT2有四个。基于生物信息学研究的全基因组测序揭示了假定的噬菌体，但我们建议进行生物学研究，以揭示这些是否是能够形成自由噬菌体颗粒并将基因传递给其他宿主的活性噬菌体。

The objective of work in my laboratory is to use the methods of genetics and genomics to reveal the basis for the astonishing degree of genetic variability which is found in bacterial populations. The over 2000 serovars of Salmonella vary dramatically, including S. enterica serovar Typhimurium which causes gastroenterites in many animals and humans, and S. enterica serovar Typhi which causes a much more serious enteric fever (Typhoid) only in humans, and thousands of other forms. I began studies in the 1960s by constructing a linkage map of the chromosome of S. Typhimurium with less than 200 genes mapped; in 2001 a collaborative effort with other labs sequenced about 4800 genes in the genome of the same bacterium. Sequence reveals that there are blocks of DNA, called Islands, in different serovars, which are present in some, but missing from others, and these produce different properties and virulence. Typhi has an Island which controls a virulence antigen; we have studied the loss of that island. In the coming grant period we have two major goals. (1) Comparative genomic analysis in enteric bacteria. We will be completing seven genomes which are being sequenced in our collaboration with Washington Univ. Genome Sequencing Center. We take part in gene annotation in these seven genomes, and overall comparisons of the genomes of all sequences to reveal phylogenetics, and to explain the basis for different phenotypes. (2) Study of the presence and role of prophages in bacterial genomes. Prophages are present in most genomes, e.g., S. Typhimurium strain LT2 has four. Whole genome sequencing reveals putative prophages based on bioinformatic studies, but we propose biological studies which will reveal if these are active prophages which can form free phage particles and transmit genes to other hosts.