לוח שנה משולב

A wide variety of chemical transformations can be induced by the application of force or stress to reactive systems. In some cases, these reactions are undesired, including some tribochemical (friction-induced) reactions and bond-breaking in polymers under stress. A large and growing set of examples shows that mechanochemistry can be harnessed for useful chemical transformations, making the case for mechanochemistry as a general-purpose tool to advance chemical innovation. In order to realize this vision, we require greater understanding of how force and stress can be focused on particular bonds and reaction coordinates, and how this enhances chemical reactivity and selectivity. In this talk, I will outline strategies for applying stress to quantum-mechanical models of reactive chemical systems and for understanding the resulting mechanochemical reaction pathways. I will also describe the development of interatomic potential models that can enable larger-scale models of mechanochemical and piezoelectric effects in molecules, 2D materials, and polar solids.

Spontaneous neuronal activity in sensory brain regions is spatiotemporally structured, suggesting that this ongoing activity may have a functional role. Nevertheless, the neuronal interactions underlying these spontaneous activity patterns, and their biological relevance, remain elusive. We addressed these questions using two-photon and light-sheet Ca2+ imaging of intact zebrafish larvae to monitor the fine structure of the spontaneous activity in the zebrafish optic tectum (the fish's main visual center. We observed that the spontaneous activity was organized in topographically compact assemblies, grouping functionally similar neurons rather than merely neighboring ones, reflecting the tectal retinotopic map. Assemblies represent all-or-none-like sub-networks shaped by competitive dynamics, mechanisms advantageous for visual detection in noisy natural environments. Furthermore, the spontaneous activity structure also emerged in “naive” tecta (tecta of enucleated larvae before the retina connected to the tectum). We thus suggest that the formation of the tectal network circuitry is genetically prone for its functional role. This capability is an advantageous developmental strategy for the prompt execution of vital behaviors, such as escaping predators or catching prey, without requiring prior visual experience.
Mutant zebrafish larvae for the mecp2 gene display an abnormal spontaneous tectal activity, thus representing an ideal control to shed light on the biological relevance of the tectal functional connectivity. We found that the tectal assemblies limit the span of the visual responses, probably improving visual spatial resolution.

Despite favorable initial response to therapy, a third of cancer patients will develop recurrent disease and succumb to it within five years of diagnosis. While there has been much progress in characterizing the pathways that contribute to stable genetic drug resistance, the mechanisms underlying early reversible resistance, also known as persisters-driven resistance, remain largely unknown. It has long been believed that persisters represent a subset of cells that happen to be non-proliferating at the time of treatment, and therefore can survive drugs that preferentially kill rapidly proliferating cells. However, in my talk I will describe a rare persister population which, despite not harboring any resistance-conferring mutation, can maintain proliferative capacity in the presence of drug. To study this rare, transiently-resistant, cycling persister population, we developed Watermelon, a high-complexity expressed barcode lentiviral library for simultaneous tracing of each cell’s clonal origin and proliferative and transcriptional states. We combine single cell transcriptomics with imaging and metabolomics to show that cycling and non-cycling persisters arise from different cell lineages with distinct transcriptional and metabolic programs. Finally, I will describe how by studying persister cells we can gain critical insights on cellular memory, fate, and evolution, which can guide the development of better anti-cancer treatments.