Searching for partners

A combination of the EMARS reaction and the application of mass spectrometry-based proteomics techniques promises to permit cell-surface molecular clustering to be analyzed under physiological conditions [Jiang et al., Proteomics 2012, 12, 54-62]. It is very likely that this approach will provide new insights into a wide range of research areas directed at understanding the cell-surface interactome.     

Searching for synthetic lethality in cancer

The incentive to develop personalised therapy for cancer treatment is driven by the premise that it will increase therapeutic efficacy and reduce toxicity. Understanding the underlying cellular and molecular basis of the disease has been extremely important in the design of these novel therapies; however, identifying new drug targets for personalised therapies remains problematic. This review describes how the biological concept of synthetic lethality has been successfully implemented to identify new therapeutic approaches and targets in models from yeast through to human cells. We also discuss how recent technical advances combined with an increased understanding of the complexity of cellular networks may facilitate therapeutic advances in the future.     

大围山里寻蝙蝠

壬午年末,北国正是银装素裹、呵气成霜的时节,我们为了进行蝙蝠系统发育研究,来到了素有“彩云之南”、“野生动植物王国“美称的云南省东南部,探访生活在祖国边陲的小鬼头。 云南省是我国蝙蝠最丰富的地区,位于屏边县的大围山是我们选择的重要目的地之一。早在上个世纪50年代,中国科学院动物所的老前辈们曾经来到这里采集了大量蝙蝠标本,正所谓“前人栽树,后人乘凉”,我们得益于这些丰富的历史资料所提供的重要信息,也使我们下定决心要来此看一看。 屏边县城是一个很小的地方,但却流露出与大城市不同的、几分难得的幽静和安逸。大围山自然保护区管理所副所长何永明先生及其同事热情欢迎我们这些慕名远道而来的探访者。     

寻找洞穴鱼

2004年12月,《人与生物圈》杂志记者、摄影师等一行三人到茂兰保护区考察。听说这里有一种非常珍稀而神秘的洞穴盲鱼——荔波盲条鳅,他们为之一振,希望能一睹荔波盲条鳅的倩影,同时也希望茂兰保护区能把这一珍稀鱼类的物种现状搞清楚,弄清这一物种究竟还存不存在,如还存在,应如何采取相应措施加强保护。管理局随即决定由我和另几位同事及摄影师组成一个精干的考察小分队,     

Searching for nuclear-mitochondrial genes

Recently, a novel strategy has been developed to identify yeast genes that are important for mitochondrial respiratory chain function. This approach found a large number of genes that were not previously thought to be involved, providing new candidate disease genes for mitochondrial disorders. These genes could cast light on the intricate relationship between genotype and phenotype in a wide range of inherited human diseases.     

Searching for schizophrenia genes

Schizophrenia is characterized by profound disturbances of cognition, emotion and social functioning. It carries a lifetime risk within the general population of approximately 1%. Genetic epidemiological studies have shown that the syndrome has a high heritability, indicating a significant genetic component to its aetiology. However, the undoubted complexity and probable heterogeneity of the disorder continue to confound research, and the precise underlying neurobiological mechanisms remain largely unknown. Although molecular-genetic approaches face formidable difficulties, the identification of susceptibility genes is likely to provide valuable insights into the aetiology and pathogenesis that could lead to the development of more effective treatments.     

Searching for Sequence Directed Mutagenesis in Eukaryotes

Sequence directed mutagenesis is a mechanism by which imperfect repeats “repair” each other to become perfect, generating mutations. This process is known to be prevalent in prokaryotes and it has been implicated in several human genetic diseases. Here we test whether sequence directed mutagenesis occurs in the protein coding sequences of eukaryotes using extensive DNA sequence data from humans, mice, Drosophila, nematodes, yeast, and Arabidopsis. Using two tests we find little evidence of sequence directed mutagenesis. We conclude that sequence directed mutagenesis is not prevalent in eukaryotes and that the examples of human diseases, apparently caused by sequence directed mutagenesis, are probably coincidental. [Reviewing Editor: Dr. Richard Kliman]     

Searching for neuroglobin's role in the brain

Neuroglobin is a small globin that plays an important role in the protection of brain neurons from ischemic and hypoxic injuries. The molecular mechanisms by which Ngb performs its physiological function are still under debate. Suggestions include oxygen storage and delivery, scavenging of NO and/or reactive oxygen species, oxygen sensing and signal transduction. In recent years, the molecular structures of Ngb with carbon monoxide bound to the heme iron and without an exogenous ligand have been solved, and interesting structural changes have been noticed upon ligand binding. Moreover, equilibrium and kinetic properties of the reactions with ligands have been examined in great detail. Here we summarize the molecular properties of Ngb and discuss them in relation to the potential physiological functions.     

Searching for new allosteric sites in enzymes

The discovery of new allosteric sites generates opportunities for the identification of novel pharmaceuticals and increases our understanding of basic biological processes. Increasingly, allosteric sites are being discovered in various families of proteins by several methods, paving the way for the development of entirely new classes of drugs with a wide range of chemotypes. New allosteric sites in enzymes have been discovered both incidentally and by directed means, and the mechanisms by which allosteric activation and inhibition occur at these sites have been investigated. By exploring recent structurally well-characterized examples, trends begin to emerge for both the modes of binding and mechanisms of inhibition.     

Searching for phylogenetic pattern in biological invasions

It has been suggested that alien species with close indigenous relatives in the introduced range may have reduced chances of successful establishment and invasion (Darwin's naturalization hypothesis). Studies trying to test this have in fact been addressing four different hypotheses, and the same data can support some while rejecting others. In this paper, we argue that the phylogenetic pattern will change depending on the spatial and phylogenetic scales considered. Expectations and observations from invasion biology and the study of natural communities are that at the spatial scale relevant to competitive interactions, closely related species will be spatially separated, whereas at the regional scale, species in the same genera or families will tend to co-occur more often than by chance. We also argue that patterns in the relatedness of indigenous and naturalized plants are dependent on the continental/island setting, spatial occupancy levels, and on the group of organisms under scrutiny. Understanding how these factors create a phylogenetic pattern in invasions will help us predict which groups are more likely to invade where, and should contribute to general ecological theory.