Behavioral adjustment of C. elegans to mechanosensory loss requires intact mechanosensory neurons.

Sensory neurons specialize in detecting and signaling the presence of diverse environmental stimuli. Neuronal injury or disease may undermine such signaling, diminishing the availability of crucial information. Can animals distinguish between a stimulus not being present and the inability to sense that stimulus in the first place? To address this question, we studied Caenorhabditis elegans nematode worms that lack gentle body touch sensation due to genetic mechanoreceptor dysfunction.

High-Reynolds Microfluidic Sorting of Large Yeast Populations.

Microfluidic sorting offers a unique ability to isolate large numbers of cells for bulk proteomic or metabolomics studies but is currently limited by low throughput and persistent clogging at low flow rates. Recently we uncovered the physical principles governing the inertial focusing of particles in high-Reynolds numbers. Here, we superimpose high Reynolds inertial focusing on Dean vortices, to rapidly isolate large quantities of young and adult yeast from mixed populations at a rate of 10 cells/min/channel.

Structural Basis for Modulation of Quality Control Fate in a Marginally Stable Protein.

The human von Hippel-Lindau (VHL) tumor suppressor is a marginally stable protein previously used as a model substrate of eukaryotic refolding and degradation pathways. When expressed in the absence of its cofactors, VHL cannot fold and is quickly degraded by the quality control machinery of the cell. We combined computational methods with in vivo experiments to examine the basis of the misfolding propensity of VHL.

Dynamic JUNQ inclusion bodies are asymmetrically inherited in mammalian cell lines through the asymmetric partitioning of vimentin.

Aging is associated with the accumulation of several types of damage: in particular, damage to the proteome. Recent work points to a conserved replicative rejuvenation mechanism that works by preventing the inheritance of damaged and misfolded proteins by specific cells during division. Asymmetric inheritance of misfolded and aggregated proteins has been shown in bacteria and yeast, but relatively little evidence exists for a similar mechanism in mammalian cells.

Cellular maintenance of nuclear protein homeostasis.

The accumulation and aggregation of misfolded proteins is the primary hallmark for more than 45 human degenerative diseases. These devastating disorders include Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. Over 15 degenerative diseases are associated with the aggregation of misfolded proteins specifically in the nucleus of cells.