Integrated Calendar

Zoom: https://weizmann.zoom.us/j/93321256211?pwd=TXNaWGw0ZjBJVGpnZUFMMFdpbElaQT09
Passcode: 379614


Crystallization plays an important role in many areas of biology, chemistry and materials science, but the underlying mechanisms that govern crystallization are still poorly understood because of experimental limitations in the analysis of such complex, evolving systems. To derive a fundamental understanding of crystallization processes, it is essential to access the sequence of solid phases produced as a function of time, with atomic-level resolution. Rationalization of crystallization processes is particularly relevant for polymorphic materials, i.e. solids that can exist as distinct crystalline forms. Indeed, polymorphism can have huge economic and practical consequences for industrial applications in pharmacy and energy because different polymorphs display different physicochemical properties. If, on the one hand, it offers great opportunities for tuning the performance of the material, on the other hand, manufacture or storage-induced, unexpected, polymorph transitions can compromise the end-use of the solid product. Interestingly, these transformations often imply the formation of metastable forms, which are receiving growing attention because they can offer new crystal forms with improved properties. Today, detection and accurate structural analysis of these – generally transient – forms remain challenging, essentially because of the present limitations in temporal and spatial resolution of the analysis, which prevents rationalization (and hence control) of crystallization processes.
In our group, we develop dynamic nuclear polarization (DNP) solid-state NMR approaches to overcome these limitations. In this contribution, I will present some of our latest results showing that cryogenic MAS NMR [1] combined with the sensitivity enhancement provided by DNP [2] can be an efficient way of monitoring the structural evolution of crystallizing solutions with atomic-scale resolution on a time scale of a few minutes. I will discuss current approaches and recent developments allowing to detect and characterize transient, metastable phases formed at the early stages of crystallization through the use of tailored DNP polarizing agents [3].
[1] P. Cerreia-Vioglio, G. Mollica, M. Juramy, C.E. Hughes, P.A. Williams, F. Ziarelli, S. Viel, P. Thureau, K.D.M. Harris, Angew. Chem. Int. Ed. 57, 6619 (2018)
[2] P. Cerreia-Vioglio, P. Thureau, M. Juramy, F. Ziarelli, S. Viel, P.A. Williams, C.E. Hughes, K.D.M. Harris, G. Mollica J. Phys. Chem. Lett. 10, 1505 (2019)
[3] M. Juramy, R. Chèvre, P. Cerreia-Vioglio, F. Ziarelli, E. Besson, S. Gastaldi, S. Viel, P. Thureau, K.D.M. Harris, G. Mollica J. Am. Chem. Soc. 143, 16, 6095 (2021)

Social interactions are essential for animals to survive, reproduce, raise their young. Over the years, my lab has attempted to decipher the unique characteristics of social recognition: what are the unique cues that trigger distinct social behaviors, what is the nature and identity of social behavior circuits, how is the function of these circuits different in males and females and how are they modulated by the animal physiological status? In this lecture, I will describe our recent progress in understanding how different parts of the brain participate in the positive and negative control of parental behavior in males and females, providing a new framework to understand the regulation of adult-infant interactions in health and disease. I will also describe how new approaches in in situ single cell transcript
omics have enabled us to uncover specific hypothalamic cell populations involved in distinct social behaviors. Finally, I will describe our most recent work uncovering how specific brain circuits are able to direct adaptive changes in behavior during sickness episodes in mice.

Host: Dr. Takashi Kawashima takashi.kawashima@weizmann.ac.il tel: 2995

Cancer cells recruit and rewire normal cells in their microenvironment to support and protect them by creating a pro-tumorigenic tumor microenvironment (TME). We lack an overarching view of how, despite being genomically stable, stromal cells in the tumor microenvironment are heterogeneously reprogrammed across time and space to promote the evolution of aggressive disease. Recent work by us and others has shown that fibroblasts in the tumor microenvironment are transcriptionally rewired to become protumorigenic cancer associated fibroblasts (CAFs). Here we hypothesize that CAFs are epigenetically modified and that these modifications lead to deregulation of signaling pathways and transcriptional circuitries that support tumorigenic growth in the neoplastic cells. We applied a sensitive method of whole genome bisulfide sequencing on a model of triple-negative breast cancer in mice to evaluate the methylome profile of CAFs compared to normal mammary fibroblasts (NMFs). We detected global changes in DNA methylation as well as distinct changes in promoter methylation between NMFs and breast CAFs in mice. These changes inversely correlated with transcriptional changes between CAFs and NMFs. We characterized potential regulators of this process, and tested their expression in CAFs in human breast cancer patients, to confirm relevance of our findings to human disease. Our findings suggest that epigenetic alterations contribute to the transcriptional rewiring of fibroblasts to CAFs. This work presents a comprehensive map of DNA-methylation in CAFs, and reveals a previously unknown facet of the dynamic plasticity of the stroma.

Protein is matter of dual nature. As a physical object, a protein molecule is a folded chain of amino acids with diverse biochemistry. But it is also a point along an evolutionary trajectory determined by the protein’s function within a hierarchy of interwoven interaction networks of the cell, the organism, and the population. Thus, a theory of proteins needs to unify both aspects, the biophysical and the evolutionary. In this talk, a physical approach to the protein problem will be described, focusing on how cooperative interactions among the amino acids shape the evolution of the protein. This view of protein as evolvable matter will be used to examine basic questions about its fitness landscape and gene-to-function map.

Background: Despite modern therapeutic modalities, ischemic heart disease remains a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of new drug development, repurposing a known drug is often an excellent alternative. Previous studies in the field of cardiac regeneration and repair revealed the importance of the immune system in modulating the disease outcome. Glatiramer-acetate (GA) is a first line drug for multiple sclerosis that has immunomodulatory and reparative effects. We therefore tested its potential application for improving heart function in murine models of cardiac injuries.
Methods: Murine models of left anterior descending coronary artery ligation were used to generate myocardial infarction (MI), followed by GA treatment at various time points post-injury. The treatment effects were evaluated using sequential echocardiography measurements and scar analysis. In vivo and in vitro settings were employed to determine GA mechanism of action in improving cardiac function post-injury, including FACS analysis, RNA sequencing, mass spectrometry, TUNEL assay, immunofluorescence and qPCR analyses.
Results: Transient treatment with GA resulted in improved cardiac function and reduced scar area in a mouse model of acute MI. In addition to its immunomodulatory function in cardiac tissue, GA induced cardiomyocyte protection, restricted cardiac fibroblast activation and enhanced angiogenesis in vivo. These effects occurred also in vitro, suggesting a direct effect of GA on cardiac cells. Importantly, GA treatment resulted also in improved left ventricular systolic function in a rat model of chronic ischemia.
Conclusions: Our findings demonstrate the beneficial effects of transient treatments with GA in models of acute and chronic cardiac ischemia, by mediating multiple reparative pathways. As GA is known as a safe drug, it should be considered for drug repurposing in patients with heart disease.

How do we strengthen memories while we sleep? In this talk, I will first focus on the question of how different sleep signatures (slow oscillations, spindles and ripples) interact and facilitate hippocampal-neocortical information transfer. I will then present recent data on actual memory content being reactivated during sleep – both naturally (endogenously) and experimentally (exogenously).

Zoom link:
https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09

Meeting ID: 954 0689 3197
Password: 750421