Amphipols: polymeric surfactants for membrane biology research

Membrane proteins classically are handled in aqueous solutions as complexes with detergents. The dissociating character of detergents, combined with the need to maintain an excess of them, frequently results in more or less rapid inactivation of the protein under study. Over the past few years, we have endeavored to develop a novel family of surfactants, dubbed amphipols (APs). APs are amphiphilic polymers that bind to the transmembrane surface of the protein in a noncovalent but, in the absence of a competing surfactant, quasi-irreversible manner. Membrane proteins complexed by APs are in their native state, stable, and they remain water-soluble in the absence of detergent or free APs. An update is presented of the current knowledge about these compounds and their demonstrated or putative uses in membrane biology.     

Evolution of the Archaean crust by delamination and shallow subduction

The Archaean oceanic crust was probably thicker than present-day oceanic crust owing to higher heat flow and thus higher degrees of melting at mid-ocean ridges. These conditions would also have led to a different bulk composition of oceanic crust in the early Archaean, that would probably have consisted of magnesium-rich picrite (with variably differentiated portions made up of basalt, gabbro, ultramafic cumulates and picrite). It is unclear whether these differences would have influenced crustal subduction and recycling processes, as experiments that have investigated the metamorphic reactions that take place during subduction have to date considered only modern mid-ocean-ridge basalts. Here we present data from high-pressure experiments that show that metamorphism of ultramafic cumulates and picrites produces pyroxenites, which we infer would have delaminated and melted to produce basaltic rocks, rather than continental crust as has previously been thought. Instead, the formation of continental crust requires subduction and melting of garnet-amphibolite--formed only in the upper regions of oceanic crust--which is thought to have first occurred on a large scale during subduction in the late Archaean. We deduce from this that shallow subduction and recycling of oceanic crust took place in the early Archaean, and that this would have resulted in strong depletion of only a thin layer of the uppermost mantle.The misfit between geochemical depletion models and geophysical models for mantle convection (which include deep subduction) might therefore be explained by continuous deepening of this depleted layer through geological time.     

TRP channels as cellular sensors

TRP channels are the vanguard of our sensory systems, responding to temperature, touch, pain, osmolarity, pheromones, taste and other stimuli. But their role is much broader than classical sensory transduction. They are an ancient sensory apparatus for the cell, not just the multicellular organism, and they have been adapted to respond to all manner of stimuli, from both within and outside the cell.     

A bivalent Huntingtin binding peptide suppresses polyglutamine aggregation and pathogenesis in Drosophila

Huntington disease is caused by the expansion of a polyglutamine repeat in the Huntingtin protein (Htt) that leads to degeneration of neurons in the central nervous system and the appearance of visible aggregates within neurons. We have developed and tested suppressor polypeptides that bind mutant Htt and interfere with the process of aggregation in cell culture. In a Drosophila model, the most potent suppressor inhibits both adult lethality and photoreceptor neuron degeneration. The appearance of aggregates in photoreceptor neurons correlates strongly with the occurrence of pathology, and expression of suppressor polypeptides delays and limits the appearance of aggregates and protects photoreceptor neurons. These results suggest that targeting the protein interactions leading to aggregate formation may be beneficial for the design and development of therapeutic agents for Huntington disease.