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Curr Biol,
2003]
microRNAs form an abundant class of 21-22 nucleotide, non-coding RNA that is common to diverse species of multicellular life. Although they are currently the subject of intense, directed study, the path toward their discovery has been dominated by chance and serendipity. In this review, I examine how these tiny molecules have risen from genetic obscurity to scientific stardom, and discuss the emerging biological functions of these novel
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Annu Rev Microbiol,
2002]
The metabolic characteristics of a yeast cell determine its life span. Depending on conditions, stress resistance can have either a salutary or a deleterious effect on longevity. Gene dysregulation increases with age, and countering it increases life span. These three determinants of yeast longevity may be interrelated, and they are joined by a potential fourth, genetic stability. These factors can also operate in phylogenetically diverse species. Adult longevity seems to borrow features from the genetic programs of dormancy to provide the metabolic and stress resistance resources necessary for extended survival. Both compensatory and preventive mechanisms determine life span, while epigenetic factors and the element of chance contribute to the role that genes and environment play in aging.
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Nature,
2007]
The acquisition of multidrug resistance is a serious impediment to improved healthcare. Multidrug resistance is most frequently due to active transporters that pump a broad spectrum of chemically distinct, cytotoxic molecules out of cells, including antibiotics, antimalarials, herbicides and cancer chemotherapeutics in humans. The paradigm multidrug transporter, mammalian P-glycoprotein, was identified 30 years ago. Nonetheless, success in overcoming or circumventing multidrug resistance in a clinical setting has been modest. Recent structural and biochemical data for several multidrug transporters now provide mechanistic insights into how they work. Organisms have evolved several elegant solutions to ridding the cell of such cytotoxic compounds. Answers are emerging to questions such as how multispecificity for different drugs is achieved, why multidrug resistance arises so readily, and what chance there is of devising a clinical solution.
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Int J Parasitol,
1995]
The chemotherapeutic control of helminth parasites is compromised by the limited number of classes of anthelmintic drugs. Discovery of novel anthelmintics is impeded by the lack of novel screening technologies that overcome the difficulties inherent in screens based on whole organism toxicity. The development and implementation of mechanism-based screens for new anthelmintics offers great promise for the revitalization of antiparasitic drug discovery. However, mechanism-based screens must be based on a thorough understanding of the proteins or processes that offer the best chance for selective chemotherapeutic intervention. Basic research on the characterization of nematode FMRF amide-related peptides (FaRPs) has revealed that these peptides are ubiquitously distributed in helminths. Chemical identification of a number of nematode FaRPs has been achieved, and these peptides have potent and profound effects on the nematode neuromuscular system. Physiological processes mediated by nematode FaRPs (and other helminth neuropeptides) offer potential targets for the discovery of novel anthelmintics.
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Philos Trans R Soc Lond B Biol Sci,
2016]
Conspicuous asymmetries seen in many animals and plants offer diverse opportunities to test how the development of a similar morphological feature has evolved in wildly different types of organisms. One key question is: do common rules govern how direction of asymmetry is determined (symmetry is broken) during ontogeny to yield an asymmetrical individual? Examples from numerous organisms illustrate how diverse this process is. These examples also provide some surprising answers to related questions. Is direction of asymmetry in an individual determined by genes, environment or chance? Is direction of asymmetry determined locally (structure by structure) or globally (at the level of the whole body)? Does direction of asymmetry persist when an asymmetrical structure regenerates following autotomy? The answers vary greatly for asymmetries as diverse as gastropod coiling direction, flatfish eye side, crossbill finch bill crossing, asymmetrical claws in shrimp, lobsters and crabs, katydid sound-producing structures, earwig penises and various plant asymmetries. Several examples also reveal how stochastic asymmetry in mollusc and crustacean early cleavage, in Drosophila oogenesis, and in Caenorhabditis elegans epidermal blast cell movement, is a normal component of deterministic development. Collectively, these examples shed light on the role of genes as leaders or followers in evolution.This article is part of the themed issue 'Provocative questions in left-right asymmetry'.