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    mRNA-based regulation: the impact of synonymous mutations on protein folding

    Date:
    24
    Monday
    February
    2025
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Harald Schwalbe
    Abstract: In this contribution, NMR and other integrated structural biology studies will b ... Read more In this contribution, NMR and other integrated structural biology studies will be presented that investigate the role of coding and non-coding mRNAs in guiding protein translation.First, we will discuss how the choice of mRNA-codons can impact protein folding. In all genomes, most amino acids are encoded by more than one codon. Synonymous codons can modulate protein production and folding, but the mechanism connecting codon usage to protein homeostasis is not known. 2D NMR spectroscopic data suggest that structural differences are associated with different cysteine oxidation states of the purified proteins, providing a link between translation, folding, and the structures of isolated proteins. Second, we investigate the coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains. Thiol groups of cysteine residues undergo S-glutathionylation and S-nitrosylation and form non-native disulfide bonds. Thus, covalent modification chemistry occurs already prior to nascent chain release as the ribosome exit tunnel provides sufficient space even for disulfide bond formation which can guide protein folding.Third, we present our work on non-coding translational riboswitches are cis-acting RNA regulators that modulate the of genes during translation initiation. Our investigation thus unravels the intricate dynamic network involving RNA regulator, ligand inducer and ribosome protein modulator during translation initiation.
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    mRNA-based regulation: the impact of synonymous mutations on protein folding Colloquium website

    Physics Colloquium

    Date:
    27
    Monday
    January
    2025
    Colloquium
    Time: 11:15-12:30
    Title: Programmable quantum many-body physics with Rydberg atom arrays
    Location: Nella and Leon Benoziyo Physics Library
    Lecturer: Dr. Tom Manovitz
    Organizer: Department of Physics of Complex Systems
    Contact: eti.shalem@weizmann.ac.il
    Abstract: Programmable quantum platforms have emerged as powerful tools for studying quant ... Read more Programmable quantum platforms have emerged as powerful tools for studying quantum many-body phenomena, with applications ranging from condensed matter and high energy physics to quantum algorithms. In this talk, I will discuss recent developments involving programmable Rydberg atom arrays, which allow for precise and coherent control of hundreds of atoms in two dimensions, along with individual addressability and reconfigurable geometry. First, I will describe explorations of ordering dynamics in a quantum magnet following a quantum phase transition. Using individual atom control, we uncover the interplay of quantum criticality and non-equilibrium phenomena, and observe long-lived oscillations of the order parameter akin to an amplitude (“Higgs”) mode, with interesting implications near the quantum critical point. I will then describe the digital realization of the Kitaev honeycomb model, including observation of an exotic non-Abelian spin-liquid, as well as the use of topological order to design a programmable fermionic simulator. These measurements introduce new avenues for the study of quantum criticality and fermionic models, respectively. Finally, I will briefly discuss future opportunities in explorations of quantum many-body physics with atom arrays, with emphasis on new frontiers in the study of quantum criticality.
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    The Evolution and Plasticity of the CONNECTOME

    Date:
    21
    Tuesday
    January
    2025
    Lecture / Seminar
    Time: 12:30-13:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Yaniv Assaf
    Organizer: Department of Brain Sciences
    Contact: naomi.moses@weizmann.ac.il
    Abstract: At every aspect of our lives, function determines structure. Just as new roads a ... Read more At every aspect of our lives, function determines structure. Just as new roads are built between developing cities, network wires are laid to accommodate faster communication demands, and social networks form around shared goals, the brain also remodels its connectome to adapt to the continuous and dynamic changes in functional demands.The connectome refers to the functional and structural characteristics of brain connectivity, spanning from the micron level (neural circuits) to the macroscopic level (long-scale pathways). This intricate network, encompassing the white matter and beyond, facilitates the transmission of information across different brain regions. When the integrity of the connectome is compromised, brain function deteriorates. Thus, the connectome is fundamental to everything the brain does.Traditionally, without the tools to explore the connectome in vivo, it was assumed to be stable and fixed. Much of white matter research focused on mapping the geographical structure of the network and its connected areas. However, advances in magnetic resonance imaging (MRI), particularly diffusion MRI, have opened a new window into the in vivo physiology of the white matter and the connectome.By measuring the microstructural properties of white matter, researchers now have the opportunity to investigate its physiology and dynamics. This presentation will demonstrate how the connectome can be measured, outline its macro- and microstructural features, and describe its evolutionary characteristics by comparing the connectomes of 100 different mammalian species. Additionally, we will explore the role of the connectome in brain plasticity and its remarkable dynamics.Light refreshments before the seminar
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    Anatomical organization of the human hippocampal system

    Date:
    05
    Sunday
    January
    2025
    Lecture / Seminar
    Time: 11:00-12:30
    Location: Belfer Building
    Lecturer: Dr. Daniel Reznik
    Organizer: Department of Brain Sciences
    Contact: ayelet.koloditsky@weizmann.ac.il
    Abstract: Animal tract-tracing studies provided critical insights into the organizational ... Read more Animal tract-tracing studies provided critical insights into the organizational principles of the hippocampal system, thus defining the anatomical constraints within which animal mnemonic functions operate. However, no clear framework defining the anatomical organization of the human hippocampal system exists. This gap in knowledge originates in notoriously low MRI data quality in the human medial temporal lobe (MTL) and in group-level blurring of idiosyncratic anatomy between adjacent brain regions comprising the MTL. In this talk, I will present our recent data, which overcame these longstanding challenges and allowed us to explore in detail the cortical networks associated with the human MTL, and to examine the intrinsic organization of the hippocampal-entorhinal system with unprecedented anatomical precision. Our results point to biologically meaningful and previously unknown organizational principles of the human hippocampal system. These findings facilitate the study of the evolutionary trajectory of the hippocampal connectivity and function across species, and prompt a reformulation of the neuroanatomical basis of episodic memory.
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    The Evolution of 7T (and Beyond) MRI in Basic Research and Clinical Practice

    Date:
    03
    Tuesday
    December
    2024
    Lecture / Seminar
    Time: 12:30-13:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Noam Harel
    Organizer: Department of Brain Sciences
    Contact: naomi.moses@weizmann.ac.il
    Details: Host: Rita Schmidt rita.schmidt@weizmann.ac.il tel:9070 For accessibility iss ... Read more Host: Rita Schmidt rita.schmidt@weizmann.ac.il tel:9070 For accessibility issues:naomi.moses@weizmann.ac.il
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    Abstract: The Center for Magnetic Resonance Research (CMRR) has been at the forefront of m ... Read more The Center for Magnetic Resonance Research (CMRR) has been at the forefront of magnetic resonance imaging (MRI) innovation, pioneering ultra-high field (7 Tesla and above) technologies that are revolutionizing brain research and clinical care. This presentation will explore CMRR's groundbreaking journey, from the first functional MRI study to development of high-resolution fMRI capabilities revealing cortical columns within the human cortex. The presentation will also explore the translation of these technologies into clinical practice, with a focus on the unique visualization capabilities of 7T MRI, particularly for enhancing the precision of Deep Brain Stimulation (DBS) procedures. By exploring the progression from the 7T system to the world’s first 10.5T human MRI, this presentation will illustrate how these transformative technologies have pushed the limits of imaging science, uncovering new insights into brain function and advancing personalized clinical care at the intersection of technology, research, and medicine.
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    Studying Ageing and Neurodegenerative Brain with Quantitative MRI

    Date:
    02
    Tuesday
    April
    2024
    Lecture / Seminar
    Time: 12:30-13:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Aviv Mezer
    Organizer: Department of Brain Sciences
    Contact: naomi.moses@weizmann.ac.il
    Details: Host: Yoav Livneh yoav.livneh@weizmann.ac.il tel:6230 For accessibility issue ... Read more Host: Yoav Livneh yoav.livneh@weizmann.ac.il tel:6230 For accessibility issues:naomi.moses@weizmann.ac.il
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    Abstract: Aging and neurodegeneration are associated with changes in brain tissue at the m ... Read more Aging and neurodegeneration are associated with changes in brain tissue at the molecular level, affecting its organization, density, and composition. These changes can be detected using quantitative MRI (qMRI), which provides physical measures that are sensitive to structural alterations. However, a major challenge in brain research is to relate physical estimates to their underlying biological sources. In this talk, I will discuss the community's efforts to use qMRI to identify biological processes that underlie changes in brain tissue. Specifically, I will highlight approaches for differentiating between changes in the concentration and composition of myelin and iron during aging. By exploring the molecular landscape of the aging and neurodegenerative brain using qMRI, we aim to gain a better understanding of these processes and potentially provide new metrics for evaluating them.
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    Chemical and Biological Physics Guest seminar

    Date:
    07
    Sunday
    January
    2024
    Lecture / Seminar
    Time: 15:00
    Title: Static and dynamic biophysical properties of tissue microstructure: Insights from advanced in vivo MRI
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr Noam Shemesh
    Organizer: Department of Chemical and Biological Physics
    Contact: daniella.goldfarb@weizmann.ac.il
    Abstract: In living systems, the tissue micro-architecture consists of myriad cellular and ... Read more In living systems, the tissue micro-architecture consists of myriad cellular and subcellular elements whose density, size/shape distributions, composition, and permeability, endow the tissue with its biological functionality. Dynamic transport mechanisms are further critical for maintaining homeostasis and supporting diverse physiological functions such as action potentials and biochemical signaling. Still, how these biophysical properties change over time and how they couple to activity, remains largely unknown. This is mainly due to the difficulty in mapping these properties in-vivo, longitudinally, and with sufficient specificity. Magnetic Resonance Imaging (MRI), with its capacity for longitudinal studies and wealth of microscopic information leading to multiple contrast mechanisms, provides an outstanding opportunity to decipher these phenomena. In this talk I will discuss our recent advances in diffusion and functional MRI, including novel pulse sequences and biophysical modeling of diffusion processes in the microscopic tissue milieu, which provide, for the first time, the sought-after specificity for density, size, and permeability of particular (sub)cellular elements in tissues. I will show new experiments in rodents proving unique power-laws predicted from biophysical models, revealing axon density and size, as well as cell body density and size, along with validations against ground-truth histology and applications in animal models of disease. Evidence for exchange between the intracellular and extracellular space will also be given, along with a first approach for quantitatively mapping permeability in tissue. I will also introduce correlation tensor MRI (CTI), a new approach for source-separation in diffusional kurtosis, that offers surrogate markers of neurite beading effects, thereby further enhancing specificity, especially in stroke. Finally, I will touch upon dynamic modulations of neural tissue microstructure upon neural activity, and provide evidence for the existence of a neuro-morphological coupling in diffusion-weighted functional MRI signals. Future vistas and potential applications will be discussed.
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    Advancing MRI: Sequences and Applications

    Date:
    04
    Thursday
    January
    2024
    Lecture / Seminar
    Time: 09:00-10:00
    Location: Max and Lillian Candiotty Building
    Lecturer: Dr. Edna Furman-Haran
    Organizer: Department of Life Sciences Core Facilities
    Contact: Edna.Haran@weizmann.ac.il

    Vision and AI

    Date:
    16
    Sunday
    July
    2023
    Lecture / Seminar
    Time: 12:15-13:15
    Title: Deep Learning Approaches for Inverse Problems in Computational Imaging and Chemistry
    Location: Jacob Ziskind Building
    Lecturer: Tomer Weiss
    Organizer: Department of Computer Science and Applied Mathematics
    Contact: karina.avadia@weizmann.ac.il
    Abstract: In this talk, I will present two chapters from my Ph.D. thesis. The core of my r ... Read more In this talk, I will present two chapters from my Ph.D. thesis. The core of my research focuses on methods that utilize the power of modern neural networks not only for their conventional tasks such as prediction or reconstruction, but rather use the information they “learned” (usually in the forms of their gradients) in order to optimize some end-task, draw insight from the data, or even guide a generative model. The first part of the talk is dedicated to computational imaging and shows how to apply joint optimization of the forward and inverse models to improve the end performance. We demonstrate these methods on three different tasks in the fields of Magnetic Resonance Imaging (MRI) and Multiple Input Multiple Output (MIMO) radar imaging. In the second part, we show a novel method for molecular inverse design that utilizes the power of neural networks in order to propose molecules with desired properties. We developed a guided diffusion model that uses the gradients of a pre-trained prediction model to guide a pre-trained unconditional diffusion model toward the desired properties. This method allows, in general, to transform any unconditional diffusion model into a conditional generative model.
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    “Parahydrogen Enhanced Magnetic Resonance - a tale of spin physics, materials and catalysis”

    Date:
    15
    Thursday
    June
    2023
    Lecture / Seminar
    Time: 00:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Stefan Glogger
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Catalysts are essential in increasing reaction rates of chemical reactions. Th ... Read more Catalysts are essential in increasing reaction rates of chemical reactions. They have not only shaped our modern world but are also used by nature in many biochemical reactions. Understanding catalytic mechanisms and developing new catalysts holds promise to e.g. solve energy challenges of our society. Before this background, I am developing new methodologies based on magnetic resonance to unravel processes in catalysis and work towards nano-materials in which nuclear spin states can be controlled during reactions. Thereby, I am making use of the technique of parahydrogen induced polarization, which is an enhancement technology in NMR, boosting signals by four orders of magnitude. This approach uses parahydrogen, a spin isomer of normal hydrogen gas that interacts with a catalyst and undergoes a chemical reaction. During this process, the spin order of parahydrogen is converted into largely enhanced magnetic resonance signals and acts as a spy molecule for the catalytic process. In recent years my group has pioneered the use of parahydrogen to study metalloenzymes and more in specific hydrogenases. Hydrogenases are considered nature's blueprint for efficient hydrogen activation catalysts. Although they represent an important class of enzymes, the catalytic mechanisms leading to hydrogen activation are not fully understood. My developed tools allowed for new insights that no other analytical technology could provide and thereby refined details of the catalytic mechanisms. Additionally, my group has been researching the development of nano-catalysts that can allow for maintaining the para-hydrogen spin order on surfaces. This promises on one side to develop new enhancement strategies in particular to boost the signal of mobile protons that can e.g. exchange with proteins or small molecules leading to their further enhancements in solution. On the other side, a precise control of nuclear spin states during chemical reactions in solution can allow for the future production of large quantities of spin-controlled chemicals such as para-water or formaldehyde in the para-state. These are chemicals found in e.g. interstellar clouds showing different ratios between ortho (triplet) and para (singlet) states as compared to earth and are thought to display different reactivities. Understanding the effect of nuclear spin states on reactions could lead to new application in chemical reactions and catalysis in the future.
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    Beyond the arcuate fasciculus: A multiplicity of language pathways in the human brain

    Date:
    13
    Tuesday
    June
    2023
    Lecture / Seminar
    Time: 12:30-13:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Michal Ben-Shachar
    Organizer: Department of Brain Sciences
    Contact: michal.ramot@weizmann.ac.il
    Abstract: Early models of the neurobiology of language targeted a single white matter path ... Read more Early models of the neurobiology of language targeted a single white matter pathway, the left arcuate fasciculus, as the critical language pathway in the human brain. Current models, supported by structural and functional imaging data, describe a more elaborate scheme of semi-parallel and bilateral white matter pathways that implement a variety of linguistic processes. In this talk, I will describe our current understanding of the language connectome, and highlight some recent additions to this scheme, including the frontal aslant tract and cerebellar pathways. I will expand on the role of ventral language pathways in extracting word structure, and on the role of dorsal and cerebellar pathways in mediating speech fluency and written text production. Our experimental approach combines diffusion MRI and targeted behavioral measurements, relating specific aspects of language processing with structural tract properties assessed in the same individual. Our findings show that cognitive associations with tractometry generalize across independent samples, languages, modalities and tasks. I will discuss the implications of our findings in the context of dual stream models of spoken and written language processing.
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    Magnetic Resonance Seminar: "Quantum sensing of out-of-equilibrium systems with magnetic resonance”

    Date:
    28
    Sunday
    May
    2023
    Lecture / Seminar
    Time: 16:00-17:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Gonzalo A. Alvarez
    Organizer: The Center for Quantum Science and Technology
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Reliable processing of quantum information is crucial for quantum technologies d ... Read more Reliable processing of quantum information is crucial for quantum technologies development. Characterizing the ubiquitous out-of-equilibrium quantum systems [1-3] is essential for designing optimal control and quantum sensing strategies. However, this task is highly challenging due to the complex high-order correlations and non-stationary nature. In this talk, I will present methods to characterize the decoherence of out-of-equilibrium quantum systems [1,4-6]. Using quantum simulations with Solid-State Nuclear Magnetic Resonance, we quantify "out-of-time order correlations" (OTOCs [2-3]) to define a critical threshold in disturbances to achieve reliable control of large quantum systems [1,4-5]. Furthermore, we develop a framework for quantum sensing the dynamics of out-of-equilibrium systems [6]. The sensor manifests spectral and non-Markovian properties, providing a quantum technology to probe time-correlation properties and mitigate the decoherence effects of non-stationary environments. [1] G. A. Alvarez, D. Suter, R. Kaiser. Science 349, 846 (2015). [2] R.J. Lewis-Swan, A. Safavi-Naini, A.M. Kaufman, A.M. Rey. Nat. Rev. Phys. 1, 627 (2019). [3] B. Swingle. Nat. Phys. 14, 988 (2018). [4] F.D. Dominguez, M.C. Rodriguez, R. Kaiser, D. Suter, G.A. Alvarez. Phys. Rev. A 104, 012402 (2021). [5] F.D. Dominguez, G.A. Alvarez. Phys. Rev. A 104, 062406 (2021). [6] M. Kuffer, A. Zwick, G.A. Alvarez. PRX Quantum 3, 020321 (2022).
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    Non-invasive Methods for Extracting Microstructural Information from Human Tissues: Implementation in a Clinical MRI Scanner

    Date:
    18
    Thursday
    May
    2023
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr Analía Zwick
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Extracting quantitative information about tissue microstructure using non-invasi ... Read more Extracting quantitative information about tissue microstructure using non-invasive methods is an exceptional challenge in understanding disease mechanisms and enabling early diagnosis of pathologies. Magnetic Resonance Imaging (MRI) is a promising and widely used technique to achieve this goal, but it still provides low resolution to reveal details of the microstructure. Recently, we have developed methods to produce images with quantitative information about the microstructure based on selective probing of spin dephasing induced by molecular diffusion restriction in cavities of the tissue microstructure [1-3]. The feasibility of the theoretical method has been demonstrated so far by first-principles experiments and simulations on typical size distributions of white matter in the mouse brain [3]. As a next step towards practical implementation, we have implemented this method in clinical scanners [4]. In this work, I present the challenges and preliminary results of this implementation in both phantoms and human volunteers. These results open up a new avenue for MRI to advance in extracting quantitative, and fast microstructural information from images. [1] A. Zwick, D. Sueter, G. Kurizki, G. A. Álvarez, Phys. Rev. Applied 14, 024088, (2020). [2] M. Capiglioni, A. Zwick, P. Jiménez, G. A. Álvarez. Proc. Intl. Soc. Mag. Reson. Med. 29, 2036 (2021) [3] M. Capiglioni, A. Zwick, P. Jiménez and G. A. Álvarez, Phys. Rev. Applied 15, 014045 (2021). [4] E. Saidman, A. Zwick, S. Tambalo, T. Feiweier, J. Jovicich, G. A. Álvarez. Proc. Intl. Soc. Mag. Reson. Med. (2023)
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    3D quantitative-amplified Magnetic Resonance Imaging (3D q-aMRI)

    Date:
    02
    Sunday
    April
    2023
    Lecture / Seminar
    Time: 16:30-17:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Itamar Terem
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Changes in blood vessel pulsation and cerebrospinal fluid dynamics cause cyclic ... Read more Changes in blood vessel pulsation and cerebrospinal fluid dynamics cause cyclic deformation of the brain, which can be altered by neurological pathologies. Various MRI techniques are available to visualize and quantify pulsatile brain motion, but they have limitations. Amplified MRI (aMRI) is a promising new technique that can visualize pulsatile brain tissue motion by amplifying sub-voxel motion in cine MRI data, but it lacks the ability to quantify the sub-voxel motion field in physical units. Here a novel 3D quantitative aMRI (3D q-aMRI) post-processing algorithm is introduced that can visualize and quantify pulsatile brain motion. To validate the algorithm, we tested it on a 3D digital phantom and on healthy volunteers. We also acquired preliminary data on participants with Alzheimer's disease and healthy aging controls. The results show that 3D q-aMRI can accurately quantify sub-voxel motion (of 0.005 pixel size) and has potential diagnostic value in identifying disease-induced biomechanical differences.
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    Biological Magnetic Resonance - From molecules to patients

    Date:
    26
    Sunday
    March
    2023
    -
    27
    Monday
    March
    2023
    Conference
    Time: 08:00
    Location: The David Lopatie Conference Centre
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: lucio.frydman@weizmann.ac.il
    Biological Magnetic Resonance - From molecules to patients Conference website

    Spatiotemporal Resolution of Conformational Changes in Biomolecules by Pulsed Electron-Electron Double Resonance Spectroscopy

    Date:
    09
    Thursday
    March
    2023
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Tobias Hett
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Proteins are highly dynamic biomolecules that can undergo ligand-induced confor ... Read more Proteins are highly dynamic biomolecules that can undergo ligand-induced conformational changes, thus often playing a crucial role in biomolecular processes. For an in-depth understanding of protein function, the conversion of one conformational state into another has to be resolved over space and time. Pulsed electron-electron double resonance spectroscopy (PELDOR/DEER) in combination with site-directed spin labelling (SDSL) is a powerful tool for obtaining distributions of interspin distances in proteins [1, 2]. It allows for measurements with Angstrom precision, but it cannot directly determine the time scale and the mechanism of the conformational change. However, coupling PELDOR with rapid freeze-quench techniques adds the time axis to the distance distribution and thus permits studying conformational changes with temporal resolution. Here, we show that the combination of Microsecond Freeze-Hyperquenching (MHQ) [3] and PELDOR resolves ligand-triggered conformational changes in proteins on the Angstrom length and microsecond time scale. It allows taking snapshots along the trajectory of the conformational change by rapid quenching within aging times of 82-668 μs, and it is applicable at protein amounts down to 7.5 nmol (75 μM, 100 μL) per time point. We applied MHQ/PELDOR to the cyclic nucleotide-binding domain (CNBD) of the MloK1 channel from Mesorhizobium loti, which undergoes a conformational change upon binding of cyclic adenosine monophosphate (cAMP). We observed a gradual population shift from the apo to the holo state on the microsecond time scale, but no distinct conformational intermediates (Fig. 1a, b). [4] Figure 1: a) Interspin distance distributions obtained at different aging times and b) the corresponding fractions of apo and holo state. c) Free-energy profile of the ligand-induced conformational change. Corroborated by measurements of ligand-binding kinetics and molecular dynamics (MD) simulations, we interpret the data in terms of a dwell time distribution. The transitions across the free-energy barriers (Fig. 1c) i.e., ligand binding and the conformational change, are on the nanosecond time scale and thus below the time resolution of the MHQ device. However, the dwell time of the apo state in complex with the cAMP ligand is in the microsecond range and can be monitored by MHQ/PELDOR. [4] Literature: [1] A.D. Milov et al., Fiz. Tverd. Tela 1981, 23, 975-982. [2] G. Jeschke, Annu. Rev. Phys. Chem. 2012, 63, 419-446. [3] A.V. Cherepanov et al., Biochim. Biophys. Acta 2004, 1656, 1-31. [4] T. Hett et al., J. Am. Chem. Soc. 2021, 143, 6981-6989.
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    High resolution in vivo NMR spectroscopy: A tale about cells, a fish and a worm

    Date:
    23
    Thursday
    February
    2023
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Andrés Binolfi
    Organizer: The Helen and Martin Kimmel Institute for Magnetic Resonance Research
    Contact: ana.naamat@weizmann.ac.il
    Abstract: To understand the functional properties of biomolecules, such a small metabolite ... Read more To understand the functional properties of biomolecules, such a small metabolites, protein or nucleic acids, we ought to study them with high resolution in their native context. NMR spectroscopy allows the direct observation of NMR-active nuclei in complex, undefined environments and can thus be employed to investigate isotopically enriched molecules inside live cells. This methodology is known as In-cell NMR and has been used to evaluate the structural properties of proteins, nucleic acids and other biomolecules in physiological environments and to resolve their functional characteristics in a cellular context. These methods have been applied to bacteria, yeasts or cultured mammalian cells. However these cells are clonally grown at high densities in artificial media, lacking the complex tissue context present in higher organisms and its associated biological activities. We funnel our efforts to extend In-cell NMR applications to in vivo conditions using zebrafish embryos and the nematode C. elegans as model organisms. We deliver 15N-isotopically enriched biomolecules, such as small compounds and proteins into fish embryos to delineate their conformational properties and enzymatic conversions. We also enrich live C. elegans with 13C atoms to directly interrogate about their metabolic compositions and enzymatic activities. Combined, these studies provide methodological advancements with regard to high resolution in vivo NMR applications.
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    Molecular MRI of brain function

    Date:
    16
    Thursday
    February
    2023
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Alan Jasanoff
    Organizer: The Helen and Martin Kimmel Institute for Magnetic Resonance Research
    Contact: ananaamat@gmail.com
    Abstract: Understanding the neural bases of behavior and cognition requires determining ho ... Read more Understanding the neural bases of behavior and cognition requires determining how mechanistically distinct processing elements combine to carry out brain function at an integrated level. In this talk, I will introduce some of our laboratory’s efforts to address this goal using a combination of molecular sensors with noninvasive wide-field imaging. In the first part of the talk, I will discuss how workhorse optical neuroimaging approaches have inspired the design of molecular MRI probes for sensing physiological variables. Some of these probes detect light, providing a means for deep-tissue MRI-assisted optical imaging. I will next introduce an alternative molecular imaging concept inspired by widely used hemodynamic functional MRI techniques. By reengineering some of the proteins and peptides involved in neurovascular coupling, it is possible to create sensitive probes for a variety of neurobiological targets. I will illustrate how this strategy can be used to elucidate patterns of information flow and neurochemically specific functional connectivity in brain circuitry, with anticipated utility for deciphering mechanisms of learning and sensory processing in rodents and primates.
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    “EPR and low-field DNP with arbitrary waveform excitation”

    Date:
    09
    Thursday
    February
    2023
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr Nino Wili
    Organizer: The Helen and Martin Kimmel Institute for Magnetic Resonance Research
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Until recently, pulse EPR was based solely on rectangular pulses. This changed w ... Read more Until recently, pulse EPR was based solely on rectangular pulses. This changed with the introduction of fast arbitrary waveform generators (AWG) that allow for pulse shaping and phase/frequency modulation at microwave frequencies. Early applications of this technology focused mainly on chirp pulses for broadband excitation and inversion within existing pulse sequences. In this talk, I will focus on Dynamic Nuclear Polarization with modulated pulse sequences in static solids. The theoretical description shows remarkable similarities with dipolar recoupling sequences in magic angle spinning (MAS) NMR. In dipolar recoupling, the pulse sequence interferes with the time-dependence of interactions due to the sample spinning. A similar phenomenon takes place in pulsed DNP, where the pulses interfere with the rotation in spin space due to the nuclear Zeeman interaction. After introducing the theoretical background, I will show results at 0.35 T/15 MHz/9.5 GHz. I will then discuss the implications for pulsed DNP at higher magnetic fields. Finally, I show and propose experiments to make use of DNP within the context of pulse EPR, i.e. for detecting hyperfine coupled nuclei in the vicinity of unpaired electrons
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    Mapping brainstem nuclei structure and connectivity in health and disease 

    Date:
    07
    Tuesday
    February
    2023
    Lecture / Seminar
    Time: 12:30-13:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Marta Bianciardi
    Organizer: Department of Brain Sciences
    Contact: naomi.moses@weizmann.ac.il
    Details: Host: Dr. Michal Ramot michal.ramot@weizmann.ac.il For accessibility issues c ... Read more Host: Dr. Michal Ramot michal.ramot@weizmann.ac.il For accessibility issues contact:naomi.moses@weizmann.ac.il
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    Abstract: Brainstem nuclei in humans play a crucial role in vital functions, such as arous ... Read more Brainstem nuclei in humans play a crucial role in vital functions, such as arousal, autonomic homeostasis, sensory and motor relay, nociception, and sleep and have been implicated in a vast array of brain pathologies, including disorders of consciousness, sleep disorders, autonomic disorders, pain, Parkinson’s disease and other motor disorders. Yet, an in vivo delineation of most human brainstem nuclei location and connectivity using conventional imaging has been elusive because of limited sensitivity and contrast for detecting these small regions using standard neuroimaging methods. In this talk, Dr. Bianciardi will present the probabilistic atlas and connectome of 31 brainstem nuclei of the arousal, motor, autonomic and sensory systems developed by her team in healthy living humans using structural, functional and diffusion-based MRI at 7 Tesla. She will also show the translatability of 7 Tesla connectivity results to conventional 3 Tesla imaging. Dr Bianciardi will conclude her seminar by presenting the first translational application of the brainstem nuclei atlas to investigate arousal and motor mechanisms in traumatic coma and premanifest synucleinopathy.
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    Reverse-engineering deep neural networks

    Date:
    19
    Thursday
    January
    2023
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Ilya Kuprov
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ananaamat@gmail.com
    Abstract: The lack of interpretability is a much-criticised feature of deep neural network ... Read more The lack of interpretability is a much-criticised feature of deep neural networks. Often, a neural network is effectively a black box. However, we have recently found a group-theoretical procedure that brings inner layer signalling into a human-readable form. We applied it to a signal processing network used in magnetic resonance spectroscopy, and found that the network spontaneously invents a bandpass filter, a notch filter, a frequency axis rescaling transformation, frequency division multiplexing, group embedding, spectral filtering regularisation, and a map from harmonic functions into Chebyshev polynomials – in ten minutes of unattended training.
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    “Functional MRI Advances at the Nexus of Acquisition, Processing, and Neuroscience”

    Date:
    12
    Thursday
    January
    2023
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Peter Bandettini
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: MRI is truly unique in that contrast and acquisition can be manipulated to highl ... Read more MRI is truly unique in that contrast and acquisition can be manipulated to highlight a many tissues and physiologic processes at a wide range of speeds and resolutions. In the early 90’s, echo-planar imaging (EPI), a rapid imaging method that required specialized hardware, enabled time series acquisition of images - each collected in tens of milliseconds. Susceptibility contrast weighting sensitized the images to subtle shifts in blood oxygenation, allowing localized brain activation changes in oxygenation to be observed in near real time, thus introducing fMRI to the world. Since this breakthrough, fMRI has continued to advance in sophistication and impact. Higher fields, higher performance gradients, and novel pulse sequences and contrasts have allowed ever more subtle effects to be observed at higher fidelity, speed, and resolution. The signal became more informative as brain activation paradigms and processing methods advanced in conjunction with our deeper understanding of artifact and signal. Importantly, our insight into brain structure and function motivated and informed the experiments and, likewise, was enriched by the results. In this talk, I’ll trace the progress in fMRI, showing how the creative tension between advances in technology, processing, and our understanding of brain activation dynamics and physiology generated many of the innovations. My talk will include retinotopy, event-related fMRI, multi-echo EPI, resting state fMRI, connectivity, representational similarity analysis, decoding, naturalistic stimuli, inter-subject correlation, high field, and layer fMRI. Lastly, I’ll describe some of the technical and practical challenges facing the field today.
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    Quantum metrology for various applications and platforms

    Date:
    09
    Monday
    January
    2023
    Lecture / Seminar
    Time: 14:30-15:30
    Location: Maurice and Gabriela Goldschleger Center For Nanophysics
    Lecturer: Dr. Tuvia Gefen (Caltech)
    Organizer: The Center for Quantum Science and Technology
    Contact: rotem.arn@weizmann.ac.il
    Abstract: The field of quantum metrology seeks to develop quantum protocols to enhance the ... Read more The field of quantum metrology seeks to develop quantum protocols to enhance the precision of measurements with applications ranging from NMR and gravimeters to calibration of quantum devices. The general tools and bounds of quantum metrology assume perfect detection. However, the detection in most quantum experimental platforms is noisy and imperfect. We fill this gap and develop a theory that takes into account general measurements . We generalize the precision bounds to account for arbitrary detection channels. We find the general form of the precision bounds and of the optimal control for pure states. We then consider quantum states in a multi-partite system and study the impact of detection noise on quantum enhancement in sensitivity. Interestingly, the achievable sensitivity depends crucially on the allowed control operations. For local optimal control, the detection noise severely degrades the sensitivity and limits any quantum enhancement to a constant factor. On the other hand, with optimal global control the detection noise can be completely removed, and the noiseless sensitivity bounds can be retrieved for a generic class of quantum states (including all pure states and symmetric states).
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    M.Sc thesis defense: “Probing the Composition and Structure of the Solid Electrolyte Interphase in Na Ion Anodes via DNP- Solid State NMR”

    Date:
    02
    Monday
    January
    2023
    Lecture / Seminar
    Time: 13:00-14:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Yuval Steinberg
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: The need for affordable large scale energy storage has risen dramatically with t ... Read more The need for affordable large scale energy storage has risen dramatically with the increase in usage of renewable energy sources. In recent years, beyond Li batteries such as Na ion batteries (SIB), gained much interest due to limited Lithium resources. However, SIBs are still far from meeting the demands in terms of electrochemical performance, rendering research on SIBs very important. During battery cycling, chemical and electrochemical processes result in the formation of an interphase between the anode and electrolyte called the solid electrolyte interphase (SEI). The effect of the SEI on electrochemical performance cannot be overstated, as its composition and structure dictate interfacial ionic transport in the battery cell. Since the SEI is very thin (10-50 nm) and is composed of disordered, organic, and inorganic phases it is extremely difficult to characterize at the atomic-molecular level. In this seminar I will present methodology developed for probing the native SEI formed in SIBs by using nuclear magnetic resonance (NMR) and signal enhanced NMR by exogenous and endogenous dynamic nuclear polarization (DNP). Employing these techniques enabled us to gain information on the chemical composition of the SEI together with important insights into the SEI’s structural gradient formed with different Na electrolytes. Correlating the compositional and structural information acquired with the SEI’s function can assist in designing SIBs with improved performance and longer lifetime.
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