Beyond induced mutants: using worms to study natural variation in genetic pathways

Induced mutants in the nematode Caenorhabditis elegans are used to study genetic pathways of processes ranging from aging to behavior. The effects of such mutations are usually analyzed in a single wildtype background: N2. However, studies in other species demonstrate that the phenotype(s) of induced mutations can vary widely depending on the genetic background. Moreover, induced mutations in one genetic background do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation. Because other wildtype Caenorhabditis spp., including C. elegans, are now available, we review how current mapping resources and methodologies within and between species support the use of Caenorhabditis spp. for studying genetic variation, with a focus on pathways associated with human disease.     

Neurobiology tools: flashdancing worms

The functional analysis of neuronal circuitry would be facilitated if researchers were able to control, over extended periods of time, the activity of genetically defined populations of neurons in vivo. New work using light-gated cation channels from green algae offers hope that this might soon be possible.     

Proteins: caught in the trap

Two independent groups have recently devised innovative methods using light to trap and manipulate particles as small as proteins.     

Dam worms

Human and animal infection rates with the Oriental schistosome have steadily declined in China over the last half-century, but the Three Gorges Dam may reverse this decline by creating new, or enlarging existing, ideal environments for the worm and its aquatic snail intermediate host.     

Membrane fusion: caught in a trap

SNAREs are small coiled-coil proteins required for specific membrane fusion events in eukaryotic cells. Recent evidence points to the existence of an inhibitory class of SNAREs, i-SNAREs, which prevent incorrect fusions from occurring, adding a further layer of regulation to the process of membrane docking and fusion.     

DNA manipulators: caught in the act

DNA is a dynamic molecule that undergoes constant changes in the cell through interactions with numerous proteins. Several classes of enzyme are specialized in promoting DNA rearrangements, including site-specific recombinases, DNA helicases, transposases and DNA topoisomerases. Recent structures of protein-DNA reaction intermediates trapped in various states of DNA remodeling, complemented by biochemical and biophysical functional studies, have enhanced our understanding of their respective mechanistic pathways.     

Receptor-ligand binding: 'catch' bonds finally caught

Leukocyte recruitment to sites of inflammation is initiated by the selectin family of adhesion receptors. Recent research reveals that P-selectin binding to its ligand exhibits 'catch' to 'slip' bond transition that may help explain the shear threshold phenomenon.     

Social evolution: war of the worms

The discovery of a non-reproductive soldier caste in a clonally reproducing trematode greatly extends the taxonomic distribution of eusociality and reaffirms the importance of relatedness in the evolution of reproductive altruism.     

Parasite role reversal: worms on trial

Asthma has reached epidemic proportions globally. This has been attributed by many to improved hygiene. The frequent failure of conventional pharmaceuticals to manage the disease has led to the introduction of parasites as a potential alternative therapy for asthma and other immunological diseases. In this article, we briefly review the immunological rationale underpinning therapeutic parasitic infection, describe recently initiated trials, and highlight potential risks and benefits of introducing parasites into patient cohorts.     

Anesthetic mechanisms: worms light the way

In the nematode C. elegans, immobility induced by the anesthetic halothane is coupled to its ability to modulate neuronal resting membrane potential, perhaps through effects on leak channels; a similar anesthetic, isoflurane, appears to work a different way.     

Secretion: kiss and run caught on film

Recent results have provided graphic support for the hypothesis that vesicle secretion involves a 'kiss-and-run' mechanism. Evanescent field microscopy has shown that, during exocytosis, intravesicular markers escape without collapse of the vesicular membrane into the surface membrane and that the empty vesicle is immediately retrieved back into the cell.     

Crawling of worms

The mechanics of a worm crawling along a flat surface is analyzed. The external forces of friction and gravity, and the internal pressure and tension, are taken into account. An equation of motion is formulated, and solutions are sought in which both the tension and the linear density are required to lie between prescribed bounds. Pulse and periodic travelling wave solutions are constructed. The maximum crawling velocity is determined, as well as the wave form which achieves it. Comparison of the results with experimental observations shows that the theory yields a maximum crawling velocity which is much larger than the observed velocity. Therefore, the theory is changed to require that the time rate of change of tension be less than a prescribed bound, rather than that the tension be bounded. With this modification, the theory agrees fairly well with the observations.     

Sleep: dozy worms and sleepy flies

Recent work on quiescent states in Caenorhabditis elegans suggests that worms exhibit behaviours reminiscent of satiety and sleep in mammals. At a molecular level, signalling through the EGF receptor and protein kinase G promotes quiescent states in both worms and flies, suggesting conserved mechanisms for sleep-like behaviours.