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)

J. Appl. Cryst.の発刊に際して

BIOE 402. Medical Technology Assessment. 2 or 3 hours. Bioentrepreneur course. Assessment of medical technology in the context of commercialization. Objectives, competition, market share, funding, pricing, manufacturing, growth, and intellectual property; many issues unique to biomedical products. Course Information: 2 undergraduate hours. 3 graduate hours. Prerequisite(s): Junior standing or above and consent of the instructor.

“Bioinformatics” 특집을 내면서

Nature relies on large molecules to carry out sophisticated chemical operations, such as catalysis, tight and specific binding, directed flow of electrons, or controlled crystallization of inorganic phases. The polymers entrusted with these crucial tasks, mostly proteins but sometimes RNA, are unique relative to other biological and synthetic polymers in that they adopt specific compact conformations that are thermodynamically and kinetically stable. These folding patterns generate “active sites” via precise three-dimensional arrangement of functional groups. In terms of covalent connectivity, the groups that comprise the active site are often widely spaced along the polymer backbone. The remarkable range of chemical capabilities that evolution has elicited from proteins suggests that it might be possible to design analogous capabilities into unnatural polymers that fold into compact and specific conformations. Since biological evolution has operated under many constraints, the functional properties of proteins and RNA should be viewed as merely exemplifying the potential of compactly folded polymers. The chemist’s domain includes all possible combinations of the elements, and the biological realm, vast and complex though it may be, is only a small part of that domain. Therefore, realization of the potential of folding polymers may be limited more by the human imagination than by physical barriers. I use the term “foldamer” to describe any polymer with a strong tendency to adopt a specific compact conformation. Among proteins, the term “compact” is associated with tertiary structure, and there is as yet no synthetic polymer that displays a specific tertiary structure. Protein tertiary structure arises from the assembly of elements of regular secondary structure (helices, sheets, and turns). The first step in foldamer design must therefore be to identify new backbones with well-defined secondary structural preferences. “Well-defined” in this case means that the conformational preference should be displayed in solution by oligomers of modest length, and I will designate as a foldamer any oligomer that meets this criterion. Within the past decade, a handful of research groups have described unnatural oligomers with interesting conformational propensities. The motivations behind such efforts are varied, but these studies suggest a collective, emerging realization that control over oligomer and polymer folding could lead to new types of molecules with useful properties. The purpose of this “manifesto” is to introduce a large audience to the broad research horizons offered by the concept of synthetic foldamers. The path to creating useful foldamers involves several daunting steps. (i) One must identify new polymeric backbones with suitable folding propensities. This goal includes developing a predictively useful understanding of the relationship between the repetitive features of monomer structure and conformational properties at the polymer level. (ii) One must endow the resulting foldamers with interesting chemical functions, by design, by randomization and screening (“evolution”), or by some combination of these two approaches. (iii) For technological utility, one must be able to produce a foldamer efficiently, which will generally include preparation of the constituent monomers in stereochemically pure form and optimization of heteropolymer synthesis. Each of these steps involves fascinating chemical challenges; the first step is the focus of this Account.

Foldamers: A Manifesto

In the past 2 decades, structural biology has transformed from a single technique used on single proteins to a multimodal integrative approach. Recently, protein structure prediction algorithms have opened new avenues to address challenging biological questions.

/pdf/structural-biology-a-golden-era-26mxnda6.pdf

Structural biology: A golden era

The structures of the new diterpene lactones trichoaurantianolides B (2), C (3) and D (4), isolated from the fruiting bodies of Tricholoma aurantium have been elucidated by manifold spectroscopic studies and, in the case of 2, confirmed by X-ray crystallographic analysis.

The Structures of Trichoaurantianolides B, C and D, Novel Diterpenes from Tricholoma aurantium.

Fluorescent Lanthanoid Complexes. New Complexes of Lanthanoids(III) with Coumarinic-3-carboxylic Acid.

BACKGROUND Protein structural rigidity was analyzed in a non-redundant ensemble of high-resolution protein crystal structures by means of the Hirshfeld test, according to which the components (uX and uY) of the B-factors of two atoms (X and Y) along the interatomic direction is related to their degree of rigidity: the atoms may move as a rigid body if uX = uY and they cannot if uX ≠ uY. RESULTS It was observed that the rigidity degree diminishes if the number of covalent bonds intercalated between the two atoms (d_seq) increases, while it is rather independent on the Euclidean distance between the two atoms (d): for a given value of d_seq, the difference between uX and uY does not depend on d. No additional rigidity decline is observed when d_seq ≥  ~ 30 and this upper limit is very modest, close to 0.015 A. CONCLUSIONS This suggests that protein flexibility is not fully described by B-factors that capture only partially the wide range of distortions that proteins can afford.

/pdf/decline-of-protein-structure-rigidity-with-interatomic-4s1ha168mf.pdf

Oliviero Carugo

Papers

Structural biology: A golden era

The Structures of Trichoaurantianolides B, C and D, Novel Diterpenes from Tricholoma aurantium.

Fluorescent Lanthanoid Complexes. New Complexes of Lanthanoids(III) with Coumarinic-3-carboxylic Acid.

Decline of protein structure rigidity with interatomic distance.

Uses and Abuses of the Atomic Displacement Parameters in Structural Biology.