Integrated Calendar

Proteins, which are at the heart of many biological processes, are involved in a variety of self-assembly processes that are controlled by various chemical and physical interactions. Quantifying the driving forces that govern these processes and particularly the trade-offs between them is essential to obtaining a more complete understanding of protein dynamics and function. In my lecture, I will discuss the molecular determinants that govern linear diffusion of proteins along DNA or along microtubules. These and other cellular processes, such as protein folding, are subject to conflicting forces some of which are regulated by post-translational modifications. Understanding the trade-offs between the stability, affinity and mobility is not only essential to decipher transport processes in the cell but also for formulating concepts for their engineering. I will discuss the power of computational models in formulating fundamental biomolecular concepts and in predicting novel principles of cellular function or for its optimization.

Alzheimer’s disease (AD) is one of the most pressing global medical issues to date with no effective therapeutic strategies. Despite extensive research much remains unknown regarding the crosstalk between brain cells and the role of non-neuronal cells in the progression of Alzheimer’s disease (AD). We use single nucleus RNA-sequencing and machine learning algorithms to build detailed cellular maps of mice and human brain and to follow molecular changes in each cell type along disease progression. Our maps revealed new disease associated states in glia cells as well as unique multi-cellular communities linked to AD. Specifically, we found a link between populations of disease-associated astrocytes (DAAs), microglia, oligodendrocytes and GABAergic neurons to AD related traits in mouse models and in post-mortem human brains. Expanding the data analysis across multiple cell types, we found co-occurrences of cellular populations across individuals, which we define as multi-cellular communities. Among these communities we discovered a unique cellular community linked to cognitive decline and Alzheimer’s disease pathology. These new insights are shaping our understanding of the unique cellular environment of the Alzheimer’s disease brains.


Zoom link to join:
https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laUUdGbWR1VFJTdz09

Meeting ID: 966 0803 3618
Password: 564068

Host: Dr. Rita Schmidt rita.schmidt@weizmann.ac.il tel: 9070

Zoom LInk: https://weizmann.zoom.us/j/97917323609?pwd=OGpCVzNKWGlCSS9lbTIyS0FtN1lHUT09

Recent experiments have demonstrated that rapid rupture fronts, akin to earthquakes, mediate the transition to frictional motion. Moreover, once these dynamic rupture fronts ("laboratory earthquakes" ) are created, their singular form, dynamics and arrest are well-described by fracture mechanics. Ruptures, however, need to be created within initially rough frictional interfaces, before they are able to propagate. This is the reason that ``static friction coefficients” are not well-defined; frictional ruptures can nucleate for a wide range of applied forces. A critical open question is, therefore, how the nucleation of rupture fronts actually takes place. We experimentally demonstrate that rupture front nucleation is prefaced by slow nucleation fronts. These nucleation fronts, which are self-similar, are not described by fracture mechanics. They emerge from initially rough frictional interfaces at a well-defined stress threshold, evolve at characteristic velocity and time scales governed by stress levels, and propagate within a frictional interface to form the initial rupture from which fracture mechanics take over. These results are of fundamental importance to questions ranging from earthquake nucleation and prediction to processes governing material failure.

The hippocampus and related medial temporal lobe structures (entorhinal cortex, perirhinal cortex, etc.) play a vital role in transforming experience into long-term memories that are then stored in the cortex, however the cellular mechanisms which designate single neurons to be part of a memory trace remain unknown. Part of the difficulty in addressing the mechanisms of transformation of short-term to long-term memories is the distributed nature of the resulting “engram” at synapses throughout the cortex. We therefore used a behavioral paradigm dependent on both the hippocampus and neocortex that enabled us to generate memory traces rapidly and reliably in a specific cortical location, by training rodents to associate the direct electrical microstimulation of the primary sensory neocortex with a reward. We found that medial-temporal input to neocortical Layer 1 (L1) gated the emergence of specific firing responses in subpopulations of Layer 5 pyramidal neurons marked by increased burstiness related to apical dendritic activity. Following learning and during memory retrieval, these neocortical responses became independent of the medial-temporal influence but continued to evoke behaviour with single bursts sufficient to elicit a correct response. These findings suggest that L1 is the locus for hippocampal-dependent associative learning in the neocortex, where memory engrams are established in subsets of pyramidal neurons by enhancing the sensitivity of tuft dendrites to contextual inputs and driving burst firing.

Zoom link to join- https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laUUdGbWR1VFJTdz09

Meeting ID: 966 0803 3618
Password: 564068
Host: Dr. Rita Schmidt rita.schmidt@weizmann.ac.il tel: 9070

I will describe how the orbit method can be developed in a quantitative form, along the lines of microlocal analysis, and applied to local problems in representation theory and global problems concerning automorphic forms. The local applications include asymptotic expansions of relative characters. The global applications include moment estimates and subconvex bounds for L-functions. These results are the subject of two papers, the first joint with Akshay Venkatesh:


https://arxiv.org/abs/1805.07750

https://arxiv.org/abs/2012.0218