לוח שנה משולב

I will describe approaches used to follow and quantify transcription kinetics from single genes in fixed and living cells, using single-molecule RNA FISH and live-cell imaging. These studies have allowed us to examine transcription at high resolution during the cell cycle and to reveal new levels of regulation. We have also generated a method to tag endogenous genes on the mRNA and protein levels, and this has allowed us to use RNA FISH to differentiate between the transcriptional activity of various alleles of the same gene in single cells, to characterize a cellular response to stress, and to screen for compounds that interfere with the stress response.

The activity of different descending systems can be de-correlated from kinematic and kinetic variables describing the motor outcome to reveal that these systems are responsible for parametric shifts in balance in the interaction between the organism and environment. Such shifts also pre-determine the origin (referent) points of spatial frames reference in which actions are produced. Parametric (referent) control can be identified at any level of action production, from the level of a single motorneuron to the level involving motoneurons of multiple muscles of the body.

Following a stroke or damage to the central nervous system, deficits in motor planning and execution may ensue, leading to a reduced capacity to use the affected upper limb to meaningfully interact with objects in the environment. A framework of disordered motor control based on reduced threshold control will be presented and considered together with cognitive and perceptual deficits underlying movement deficits.

The concept of “colloidal molecules” builds on the analogy between colloidal particles and molecules. For about a hundred years, colloidal particles have been used as model systems for studying atoms or molecules. Recently, this approach has been changed: interactions between molecules have been used to model nanoparticle self-assembly. In particular, polymer science offers unique strategies to address the challenges in nanoparticle assembly.

By using lessons of polymer physics and chemistry, we developed new paradigms for nanoparticle patterning and self-organization. A pinned micelle approach has been utilized to create colloidal molecules. A striking resemblance between block copolymers and amphiphilic nanoparticles enabled nanoparticle organization in nanostructures with varying morphologies, all mapped by state diagrams. A marked similarity between step-growth polymerization and nanoparticle self-assembly enabled growth of nanopolymers, with a quantitative prediction of the architecture of linear, branched, and cyclic nanostructures, their aggregation number and size distribution, as well as the formation of structural isomers. Building on this similarity, we proposed the concept of colloidal chain stoppers and copolymers. For linear chains of plasmonic nanoparticles, we discovered new optical properties.
This work has far-reaching implications for the molecular world (by offering simple, easy to visualize nanoscale models for polymerization reactions), and for the nano-world (by providing a polymer approach to nanostructures with structure-dependent electronic, optical, and magnetic properties).

Sleep may be universal in the animal kingdom. Yet, the roles of sleep and the underlying reason for this universality remain controversial. The roundworm Caenorhabditis elegans is the simplest model system in which these questions can be addressed. This talk will describe consequences of disruptions to worm sleep, which can range from compensation for mild disruptions to long lasting ill effects of severe but nonlethal deprivation. A key feature of sleep is its intricate compensatory mechanisms: following disruptions, ‘restoring forces’ extend or modify sleep to compensate for the loss. Weak and intermediate perturbations reveal mechanistically distinct manners by which small losses of worm sleep are compensated for. Stronger perturbations, causing substantial but nonlethal sleep loss, can result in long-term deficits to neural circuits and other cell types. We found that unfolded protein responses (UPRs) were triggered by worm sleep deprivation. These protective responses are indicative of the type of damage inflicted: compromising them exacerbates the manifestations of worm fatigue. The simplicity of C. elegans enabled comparing their potential importance in different circuits and tissues. Interestingly, distinct UPRs affected different neural circuits. Therefore, worm fatigue and the mechanisms that mitigate it point to core functions of sleep in this phylogenetically ancient model organism.