Integrated Calendar

The DNA in a human cell which is ~3 meters long is packed in a tiny nucleus of ~10 μm radius. The DNA is surrounded by thousands of proteins, and it is highly dynamic while taking part in the process of protein expression and cell division. Nevertheless, it must stay organized to prevent chromosome entanglement. Studying this nanometer – micrometer scale structure is difficult, as it falls short of the optical resolution, while electron microscopy is limited due to the need to fixate the sample.
We therefore adopted various methods for studying the organization of the genome in the nucleus, including live-cell imaging, time-resolved spectroscopy and single molecule methods such as AFM. It allowed us to identify that a protein, lamin A, forms chromatin loops thereby restricting the chromatin dynamics in the whole nucleus volume. Based on the results, we conclude that the organization of the DNA in the nucleus is based on a “DNA matrix”, a structure that we describe here for the first time. The experimental methods we use necessitate the use of biophysical modeling based on Smoluchowski equation, modified diffusion equations and polymer physics.
I will describe the problem, the methods we use, the results and the conclusions as described above.

I discuss fundamental differences between the physical concepts of the globally coordinated and directed migration of cells on resilient tissue surfaces and in soft tissue, such as the brain. Cell locomotion on resilient surfaces is driven by solitary actin gelation pulses and myosin motors while microtubules and associated motors guide the global polarization of the cell
The motion on surfaces is driven by protrusions forces generated by solitary actin gelation pulses that are emitted from adhesion domains, acting as biochemical reaction and force transmission centers. I describe the formation of functional membrane domains as a paradigm of the logistically controlled self-assembly of functional domains in membranes.
In soft tissue of developing brains cell locomotion is driven by spreading of protrusions along long fibers protruding from glial cells followed by retraction of the nucleus which is powered by dynein motors.

Since the discovery of electronic thermal and shot noises a century ago, these two forms of fundamental noise have had an enormous impact on science and technology. They are regarded as valuable probes for quantum and thermodynamic quantities, but also as an undesired noise in electronic devices. While electronic thermal (Johnson–Nyquist) noise is activated by temperature, electronic shot noise is generated by a voltage difference. Recently, we identified a fundamental electronic noise contribution that is generated by temperature difference across nanoscale conductors. This noise, which we term as delta-T noise, is measured in atomic and molecular junctions, and analyzed theoretically using the Landauer–Büttiker–Imry formalism. The delta-T noise can be used to detect temperature differences across nanoscale conductors without the need for fabricating sophisticated local probes. This noise is also relevant for modern electronics! , since temperature differences are often unintentionally generated across electronic components. Taking into account the overlooked contribution of the delta-T noise in these cases, can be important for designing high performance electronics at the nanoscale.

This work was done in collaboration with the research groups of Dvira Segal (Toronto U.) and Abraham Nitzan (Tel Aviv U. & Penn).

The ubiquitin-proteasome system represents the major route by which the cell degrades unwanted proteins. E3 ubiquitin ligases (E3s) play a crucial role in providing specificity to this process, interacting with their substrates by recognizing specific short peptide motifs termed degrons. Despite their central role in proteostasis, to date only a handful of degrons have been identified and a facile technology to characterize them is lacking. Using a strategy combining Global Protein Stability (GPS) profiling with a synthetic human peptidome, we identified thousands of peptides containing degron activity. Interestingly, we found that the stability of many proteins is regulated through degrons located at their C-terminus, and utilizing CRISPR screening and computational approaches, we characterized the pathways regulating C-terminal degradation. Proteome analysis revealed that eukaryotic proteomes are depleted of proteins bearing C-terminal degron motifs, suggesting that the recognition of C-terminal degrons by E3s has sculpted eukaryotic proteomes through evolution.