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Experience from the environment is represented by neuronal activity patterns in the brain. Inside neurons, complex protein signaling cascades provide molecular instructions for structural and functional plasticity. However, we still lack a clear understanding of spatial and temporal activity patterns of protein signaling within intact neuronal circuits.I will describe an approach to visualize protein signaling dynamics using a combination of biosensor engineering and two-photon fluorescence lifetime imaging. I will describe how we use this approach to develop optical tools to monitor vital protein targets (PTEN, MeCP2, autophagy) for regulation of E/I balance, genomic integrity, or synaptic structure. Our overall goal is to understand how key protein signaling networks orchestrate the development and function of neuronal circuits in the healthy brain. We believe this is an essential first step towards identifying the seed process initiating neuronal dysfunction in a variety of brain pathologies.    

Single-molecule force spectroscopy (SMFS) enables high-resolution insights into the kinetics and mechanisms of biomolecular interactions. In this talk, I will present how SMFS, helps uncover key principles in nucleic acid and protein folding. Examples discussed will include the microsecond invasion kinetics of toehold-mediated strand displacement (TMSD) of DNA and RNA as well as mRNA-Roquin interactions, which regulate mRNA degradation via specific 3’UTR hairpin structures. Finally, we study chaperone-mediated unfolding of the glucocorticoid receptor (GR), demonstrating how Hsp70/Hsp40 unfolds GR in discrete ATP-driven steps, stabilizing novel intermediates and acting as an unfoldase. These studies showcase SMFS as a powerful tool to resolve biomolecular dynamics providing new insights into RNA structure-function relationships and chaperone-mediated protein regulation.

In this seminar, two new models will be presented. The first new model is a first-principles description of the propagation of light in a cloud, based on a classical solution to Maxwell's equations rather than radiative transfer theory. The second new model is a fully three-dimensional, time-dependent model of the regions of possible sprite inception in the mesosphere, based on the classical method of images from electrostatics rather than finite differencing in space. The reason why each model is unique, the problems each model can solve, and the kinds of results each model can produce will be discussed

Cell-cell communication is essential for growth, development and function. Cells can communicate mechanically by responding to mechanical deformations generated by their neighbors in the extracellular matrix (ECM).We use a 2D cardiac tissue model to study the role of mechanical communication between cardiac cells in the normal conduction wave. We quantify the mechanical coupling between cells in a monolayer and use this to identify a critical threshold of mechanical coupling, below which spiral waves are induced in the tissue. We demonstrate that normal conduction wave can be recovered only using mechanical stimulation. We further show that mechanical coupling reduces the sensitivity to geometrical defects in the tissue.We show that due to the dynamic viscoelastic properties of collagen hydrogels (a major component of the cardiac ECM), the shape of the mechanical signal changes in a frequency dependent manner as it propagates through the gel, leading to a frequency dependent mechanical communication. Moreover, we show that the sensitivity of cardiac cell response to the shape of the mechanical signal results from its sensitivity to the loading rate. We also show that an optimal loading rate exists for mechanical communication, implying that there are ideal viscoelastic properties for effective mechanical communication.FOR THE LATEST UPDATES AND CONTENT ON SOFT MATTER AND BIOLOGICAL PHYSICS AT THE WEIZMANN, VISIT OUR WEBSITE: https://www.biosoftweizmann.com/

There are two major classes of theories about the basal ganglia. The first class hypothesizesthat the basal ganglia are the site where cortical sensorimotor and dopaminergic rewardinformation interact to potentiate and select actions. These theories predict that contentspecificity of information emerges from within the basal ganglia. The second class oftheories posits that information is manipulated within the basal ganglia through processessuch as dimensionality reduction. These theories are primarily based on the fact that thereis a large reduction in the number of neurons from the input to the output stages of the basalganglia. These theories posit that there are changes in the coding properties of neuronsrather than the emergence of content specificity.In this talk, I will present a set of studies where we analyzed the eye movement system ofmonkeys to compare single-neuron activity in the basal ganglia with activity in thecerebellum and the frontal cortex. We used tasks that manipulated both eye movementsand expected rewards. We found that rather than coding specific sensorimotor or rewardparameters, the basal ganglia were unique in how they coded these parameters, both interms of the signal-to-noise ratio of responses and in the variety of their temporal patterns.These results strongly suggest that the basal ganglia play a role in manipulating rather thangenerating reward and sensorimotor signals.

The pre-industrial Holocene is unique among pastinterglacials due to a modest, but notable increase inatmospheric CO2 and methane (CH4) during the latter halfof the period despite an expected decrease given orbitalparameters. Although the causes for this increase,anthropogenic or natural are debated, all climate modelssimulate an increase in global mean temperature inresponse to the increase in the greenhouse gases. Yet,many proxy reconstructions, interpreted to reflect themean annual temperatures, indicate peak temperatures inthe first half of the Holocene, arguably exceeding modernmean annual temperatures followed by cooling through thepreindustrial period. This significant model-datadiscrepancy, known as the Holocene temperatureconundrum, and the debate on the cause of the CO2increase has undermined confidence in future climatemodel predications. In this talk I’ll offer new perspectiveson both issues.