抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

Rapid improvements in sequencing and array-based platforms are resulting in a flood of diverse genome-wide data, including data from exome and whole-genome sequencing, epigenetic surveys, expression profiling of coding and noncoding RNAs, single nucleotide polymorphism (SNP) and copy number profiling, and functional assays. Analysis of these large, diverse data sets holds the promise of a more comprehensive understanding of the genome and its relation to human disease. Experienced and knowledgeable human review is an essential component of this process, complementing computational approaches. This calls for efficient and intuitive visualization tools able to scale to very large data sets and to flexibly integrate multiple data types, including clinical data. However, the sheer volume and scope of data pose a significant challenge to the development of such tools.

Integrative Genomics Viewer

A complementary DNA for the Aequorea victoria green fluorescent protein (GFP) produces a fluorescent product when expressed in prokaryotic (Escherichia coli) or eukaryotic (Caenorhabditis elegans) cells. Because exogenous substrates and cofactors are not required for this fluorescence, GFP expression can be used to monitor gene expression and protein localization in living organisms.

http://science.sciencemag.org/content/sci/263/5148/802.full.pdf

Green fluorescent protein as a marker for gene expression

We have constructed a series of plasmid vectors (pBAD vectors) containing the PBAD promoter of the araBAD (arabinose) operon and the gene encoding the positive and negative regulator of this promoter, araC. Using the phoA gene and phoA fusions to monitor expression in these vectors, we show that the ratio of induction/repression can be 1,200-fold, compared with 50-fold for PTAC-based vectors. phoA expression can be modulated over a wide range of inducer (arabinose) concentrations and reduced to extremely low levels by the presence of glucose, which represses expression. Also, the kinetics of induction and repression are very rapid and significantly affected by the ara allele in the host strain. Thus, the use of this system which can be efficiently and rapidly turned on and off allows the study of important aspects of bacterial physiology in a very simple manner and without changes of temperature. We have exploited the tight regulation of the PBAD promoter to study the phenotypes of null mutations of essential genes and explored the use of pBAD vectors as an expression system.

Tight regulation, modulation, and high-level expression by vectors containing the arabinose PBAD promoter.

The bacteria cell envelope is a complex multilayered structure that serves to protect these organisms from their unpredictable and often hostile environment. The cell envelopes of most bacteria fall into one of two major groups. Gram-negative bacteria are surrounded by a thin peptidoglycan cell wall, which itself is surrounded byan outer membrane containing lipopolysaccharide. Gram-positive bacteria lack an outer membrane but are surrounded by layers of peptidoglycan many times thicker than is found in the Gram-negatives. Threading through these layers of peptidoglycan are long anionic polymers, called teichoic acids. The composition and organization of these envelope layers and recent insights into the mechanisms of cell envelope assembly are discussed.

/pdf/the-bacterial-cell-envelope-o3k9u4ycci.pdf

The Bacterial Cell Envelope

Experiments With Gene Fusions

Global perspective Cross regulation and the phosphate regulon Complex phosphate regulation by sequential switches in B subtilis Antibiotic biosynthesis in Streptomyces Genetic switches controlling sporulation in B subtilis The mechanism of the EnvZ-OmpR response to osmotic stress Two-component switches in the caulobacter cell cycle Nitrogen regulation in E coli Hexosephosphate uptake in E coli The mechanism of NtrC stimulation of transcription Mechanism of transcription activation and repression by Spo0A Control of Salmonella typhimurium virulence Regulation of Agrobacterium tumifaciens virulence Control of nitrogen fixation The nitrate reductase system of E coli Degradative enzyme synthesis in B subtilis The vancomycin resistance story Alginate production in Pseudomonas Regulation of anaerobiosis in E coli Regulation of gene transfer in E coli Communication modules in signal transducing genetic switches The structure of response regulator modules The mechanism of the phosphotransfer reaction Control of chemotaxis Myxococcus frizzy genes Conjugal DNA transfer in Bacteriodes

Two-component signal transduction

Identification of a Multicomponent Complex Required for Outer Membrane Biogenesis in Escherichia coli

The outer membrane of gram-negative bacteria such as Escherichia coli serves as a protective barrier that controls the influx and efflux of solutes. This allows the bacteria to inhabit several different, and often hostile, environments. The assembly of the E. coli outer membrane has been difficult to study using traditional genetic and biochemical methods, and how all its components reach the outer membrane after being synthesized in the cytoplasm and cytoplasmic membrane, how they are assembled in an environment that is devoid of an obvious energy source, and how assembly proceeds without disrupting the integrity of this essential cellular structure are all fundamental questions that remain unanswered. Here, we review the new approaches that have led to the recent discovery of components of the machinery involved in the biogenesis of this distinctive cellular organelle.

Advances in understanding bacterial outer-membrane biogenesis

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