לוח שנה משולב

Between 60 to 90% of the drugs that successfully pass animal trials fail in human clinical trials. This poor statistic demonstrates the urgent need for a human-relevant model. Micro-engineered cell culture models, termed Organs-on-Chips, have emerged as a new tool to recapitulate human physiology and drug responses. Multiple studies and research programs have shown that Organs-on-Chips can capture the multicellular architectures, vascular-parenchymal tissue interfaces, chemical gradients, mechanical cues, and vascular perfusion of the body. Accordingly, these models can reproduce tissue and organ functionality and mimic human disease states to an extent thus far unattainable with conventional 2D or 3D culture systems. In this talk, we will present two approaches of using this technology. The first, will demonstrate how drug can be tested by linking of 8 human-Organ-on-a-Chip and showing results that are comparable to clinical data. Furthermore, we demonstrate how to exploit the micro-engineering technology in a novel system-level approach to decompose the integrated functions of the neurovascular unit into individual cellular compartments, while retaining their paracellular metabolic coupling. In addition, we will present how these advanced models can be integrated as bio-hybrid-robots.

Ice melts at 0 [˚C], however, water can be super-cooled homogeneously down to ~-40 [˚C] without freezing. The ability to control the temperature of freezing of super-cooled water is highly important in many scientific sub-fields. Freezing can be induced at higher temperatures by the application of electric fields (known as electro-freezing). Despite the importance of the process of electro-freezing, its mechanism at the molecular level is still not fully understood. Recently, icing experiments performed by our group have demonstrated that electro-freezing comprises of the interactions of an electric field with specific ions of trigonal planar configuration, creating arm-chair hexagons that mimic the hexagons of the crystal ice. In my research, I investigated the effect of electro-freezing of super-cooled water on silver and copper electrodes. I found that the mechanism of electro-freezing of super-cooled water as induced by the silver electrodes is very complex and irreproducible. In contrast, the high icing temperature (~-4 [˚C]) on the copper (111) face is induced primarily by a mechanism of epitaxy.

Tba..

The Mediterranean region stands out among other subtropical regions in its projected drying response to
the global rise in atmospheric greenhouse gas concentrations. This drying trend has already emerged out
of the normal, random climate variability in the sensitive Eastern Mediterranean (EM) region. To better
understand the dynamical mechanisms responsible for this regional sensitivity, we turn to past protracted
EM drying states during warm geological epochs. A unique view of the historical and pre-historical
hydroclimate of the EM-Levant has been gleaned from the continued study of the sedimentary and
geochemical record left by the lakes that filled the tectonic basin of the Dead Sea. We revisit the Late
Quaternary sediment record retrieved during the 2010-2011 Dead Sea Deep Drilling Project (DSDDP). The
sediments clearly indicate that the Levant was drier during past warm interglacials than during the adjacent
glacials but nonetheless experienced large variations in the intensity of the regional aridity. During each
interglacial, extended thick deposits of salts accumulated at the Lake bottom, during millennia of
significant regional aridity and severely reduced Mediterranean rains. These dry states were interrupted
by extended wet intervals, fed by rains that were supplied by a blend of tropical and Mediterranean
moisture. To understand the underlying causes of the EM-Levant interglacial hydroclimate variations, we
put the Dead Sea record in the context of the Northern Hemisphere orbital insolation variations and their
impact on the global climate system. We show that the changes in EM hydroclimate portrayed by the
DSDDP record during the interglacials, are entirely consistent with the response of the North Atlantic
Ocean and the overlying atmosphere and surrounding land areas to the changes in the latitudinal insolation
gradient, as determined by climate models and evident by surface temperature proxies. This perspective
provides new information regarding the dynamical processes responsible for the ongoing, greenhouse
gas forced, EM drying.

Single-molecule spectroscopy, combined with fluorescence resonance energy transfer, has been intensively utilized for studying the structural dynamics of protein, DNA, and RNA. However, observation of the dynamics on the microsecond timescale is challenging due to the low efficiency of collecting photons from a single molecule. To realize quantitative investigations of structural dynamics with a sub-microsecond time resolution, we developed new single-molecule spectroscopy, i.e., two-dimensional fluorescence lifetime correlation spectroscopy (2D FLCS). In this 2D FLCS, we use a high-repetition short pulse laser for photoexcitation and analyze the correlation of the fluorescence lifetime from the donor of a FRET pair. The obtained information is represented in the form of a 2D fluorescence lifetime correlation map using the inverse Laplace transform. 2D FLCS can visualize the structural dynamics of complex molecules in the equilibrium condition with a sub-microsecond resolution at the single-molecule level.
In this presentation, I will talk about the principle of 2D FLCS and its application to the study of the structural dynamics of protein, DNA, and RNA, in particular, the most recent study on the folding/unfolding dynamics of an RNA riboswitch. Based on the observed microsecond folding dynamics, we proposed the molecular-level mechanism for transcription control by the riboswitch.