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

Date:
11
Monday
November
2024
Colloquium
Time: 11:00-12:15
Location: Gerhard M.J. Schmidt Lecture Hall
Lecturer: Prof. Harald Schwalbe
Organizer: Department of Chemical and Biological Physics
Contact: sarah.amzallag@weizmann.ac.il
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

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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 & Dr. Amir Seginer
    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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    Time Domain and High Frequency DNP Experiments

    Date:
    08
    Thursday
    December
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Robert G. Griffin
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Dynamic nuclear polarization (DNP) has become an invaluable tool to enhance sens ... Read more Dynamic nuclear polarization (DNP) has become an invaluable tool to enhance sensitivity of magic angle spinning (MAS) NMR, enabling the study of biomolecules and materials which are otherwise intractable. In this presentation we explore some new aspects of time domain DNP experiments and their applications. One of the main thrusts of DNP was to provide increased sensitivity for MAS spectroscopy of membrane and amyloid protein experiments. A problem frequently encountered in these experiments is the broadened resonances that occur at low temperatures when motion is quenched. In some cases it is clear that the proteins are homogeneously broadened, and therefore that higher Zeeman fields and faster spinning is required to recall the resolution. We show this is the case for MAS DNP spectra of Ab1-42 amyloid fibrils where the resolution at 100 K is identical to that at room temperature. Furthermore, we compare the sensitivity of DNP and 1H detected experiments and find that DNP, even with a modest ℇ=22, is ~x6.5 times more sensitive. We have also investigated the frequency swept-integrated solid effect (FS-ISE) and two recently discovered variants – the stretched solid effect (SSE) and the adiabatic solid effect (ASE). We find that the latter two experiments can give up to a factor of ~2 larger enhancement than the FS-ISE. The SSE and ASE experiments should function well at high fields. Finally, we discuss two new instrumental advances. First, a frequency swept microwave source that permits facile investigation of field profiles. It circumvents the need for a B0 sweep coil and the compromise of field homogeneity and loss of helium associated with such studies. This instrumentation has permitted us to elucidate the polarization transfer mechanism of the Overhauser effect, and also revealed interesting additional couplings (ripples) in field profiles of cross effect polarizing agents. Second, to improve the spinning frequency in DNP experiments, we have developed MAS rotors laser machined from single crystal diamonds. Diamond rotors should permit higher spinning frequencies, improved microwave penetration, and sample cooling.
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    Atomic Resolution Structures of Amyloid Fibrils - Ab1-42 , Ab1-40 and b2-microglobulin

    Date:
    05
    Monday
    December
    2022
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Robert Guy Griffin
    Organizer: Faculty of Chemistry
    Contact: sarah.amzallag@weizmann.ac.il
    Abstract: Many peptides and proteins form amyloid fibrils whose detailed molecular structu ... Read more Many peptides and proteins form amyloid fibrils whose detailed molecular structure is of considerable functional and pathological importance. For example, amyloid is closely associated with the neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. We review the macroscopic properties of fibrils and outline approaches to determining their microscopic structure using magic angle spinning (MAS) NMR with 2D and 3D dipole recoupling experiments involving spectral assignments and distance measurements. Key to obtaining high resolution is measurement of a sufficient number of NMR structural restraints (13C-13C and 13C-15N distances per residue). In addition, we demonstrate the applicability of 1H detection and dynamic nuclear polarization (DNP) to amyloid structural studies. We discuss the structures of three different amyloids: (1) fibrils formed by Ab1-42, the toxic species in Alzheimer’s, using >500 distance constraints; (2) fibrils of Ab1-40, a second form of Ab with a different structure, and (3) a structure of fibrils forned by b2-microglobulin, the 99 amino acid protein associated with dialysis related amylosis, using ~1200 constraints. Contrary to conventional wisdom, the spectral data indicate that the molecules in the fibril are microscopically well ordered. In addition, the structures provide insight into the mechanism of interaction of the monoclonal antibody, Aducanumab, directed against Ab amyloid.
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    Atomic Resolution Structures of Amyloid Fibrils - Ab1-42 , Ab1-40 and b2-microglobulin Colloquium website

    “Investigating the Surface Dynamics of Ions at the Anode-Electrolyte Interface using NMR Spectroscopy”

    Date:
    01
    Thursday
    December
    2022
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Shakked Schwartz
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: High-Performance, Rechargeable Li-ion Batteries (LIBs) are key to the global tra ... Read more High-Performance, Rechargeable Li-ion Batteries (LIBs) are key to the global transition from fossil fuels to renewable energy sources. LIBs utilizing lithium metal as the anode are particularly exciting due to their exceptional energy density and redox potential, yet their advancement is hindered by growth of metallic filaments and unstable surface layers. Efficient cationic transport, which is crucial for battery performance, largely depends on the heterogeneous and disordered interphase formed between the anode and the electrolyte during cycling. Directly observing this interphase as well as the dynamic processes involving it is a great challenge. Here we present an approach to elucidate these dynamic processes and correlate them with the corresponding interfacial chemistry, focusing on the first step of cationic transport: surface adsorption. Employing Dark State Exchange Saturation Transfer (DEST) by 7Li NMR, we were able to detect the exchange of Li-ions between the homogenous electrolyte and the heterogeneous surface layer, highlighting the hidden interface between the liquid and solid environments. This enabled determination of the kinetic and energetic binding properties of different surface chemistries, advancing our understanding of cationic transport mechanisms in Li-ion batteries. 
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    Mechanistic impact of microsecond oligomerization on minutes/hours aggregation of huntingtin studied by NMR – relevance to potential treatment avenues for Huntington’s disease

    Date:
    09
    Wednesday
    November
    2022
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. G. Marius Clore
    Organizer: Department of Chemical and Structural Biology
    Contact: nicole.dorfman@weizmann.ac.il

    "In search for speed and resolution in (functional) neuroimaging at 7T and up"

    Date:
    03
    Thursday
    November
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Benedikt A Poser
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: 7T MRI has proven itself as a great tool for neuroscientific investigation and h ... Read more 7T MRI has proven itself as a great tool for neuroscientific investigation and has been embraced by many researchers for both structural and functional neuroimaging. This talk will focus on acquisition for functional MRI at UHF. Gradient-echo BOLD fMRI is a long- and well-established tool for mapping brain activation in general neuroscience applications, owing to its robustness, acquisition speed and high sensitivity. With the signal change being driven by local deoxyhemoglobin content as a composite effect of the blood flow (CBF), blood volume (CBV) and oxygen uptake (CMRO2) response to neuronal activation, there is an overall weighting towards the draining vasculature as we go up in field strength. The super-linear sensitivity gains with B0 thus come at the expense of specificity, and this makes alternative measures such CBV or CBF more attractive, especially when aiming to resolve activation to laminar or columnar details with submillimetre resolutions. Making these techniques routinely useful, however, poses new acquisition-methodological challenges. In this talk I will discuss some of the advances in non-BOLD and non-echo-planar fMRI acquisition, with some focus on lifting the coverage limitations of VASO fMRI and CBF/ASL with parallel imaging, as well as non-Cartesian approaches to CBV and CBF measurement. Finally, I will touch on the topic of parallel RF transmission which undoubtedly play a role in future methodology and once more operator- and researcher-friendly implementations are available
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    "Using DEER and RIDME for studies of proteins and nucleic acids"

    Date:
    27
    Thursday
    October
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr Janet Lovett
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Abstract: Pulsed dipolar spectroscopy methods like DEER and RIDME are proving u ... Read more Abstract: Pulsed dipolar spectroscopy methods like DEER and RIDME are proving useful for solving hitherto unsolvable problems in structural biology. However, these methods are still being developed and improved upon. The work I shall present will be some improvements we are making to the methods and methodology within our lab. These range from investigating limits or new measurement regimes, to exploring new spin labelling methods. Some recent work-in-progress results will be shown on a range of biological samples including calmodulin, RNA and peptides.
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    Pulsed Dipolar EPR Spectroscopy: Following Conformational Changes of Biomacromolecules with Time and In Cells

    Date:
    22
    Thursday
    September
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Olav Schiemann
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Details: The function of biomacromolecules is linked to their structure and dynamics. Pul ... Read more The function of biomacromolecules is linked to their structure and dynamics. Pulsed Dipolar Electron Paramagnetic Resonance Spectroscopy (PDS) in combination with site directed spin labeling is a versatile tool to resolve the involved conformational changes in proteins, nucleic acids and their complexes. In the talk, this will be demonstrated on example of CRISPR/Cas 13a. However, the PDS measurements are usually done in the frozen state, meaning that the time scale of the conformational change is lost. We therefore combined PDS with a Microsecond freeze HyperQuench (MHQ) setup by which we were able to resolve the movement of an -helix with microsecond time and Angstrom length resolution. Finally, it is highly desirable to follow the conformational change under as natural conditions as possible, meaning within cells and at natural concentrations. We address this challenge by using a new type of label, i.e., trityl radicals, which are stable within cells and enable recording PDS data of biomacromolecule within cells down to nanomolar concentrations.
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    Ph.D thesis: Pushing the envelope of high field DNP-NMR methodology towards functional materials

    Date:
    20
    Wednesday
    July
    2022
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Asya Svirinovsky
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Functional materials are the main building blocks of advanced technologies based ... Read more Functional materials are the main building blocks of advanced technologies based on energy storage and conversion systems essential for our modern life including batteries, solar cells, and heterogeneous catalysis. Improvements in materials performance and development of new materials rely on our ability to obtain structure-function correlation as well as understand degradation processes when the materials are integrated into a device. To this end, advanced analytical tools that can provide information at the atomic level are essential. Solid-state nuclear magnetic resonance (ssNMR) spectroscopy is well suited for this task, especially when equipped with high sensitivity by Magic Angle Spinning - Dynamic Nuclear Polarization (MAS-DNP). However, to date, the majority of materials studied by MAS-DNP were non-reactive and non-conductive materials with DNP from exogenous sources of polarization such as nitroxide radicals. This approach cannot be simply extended to functional materials as the properties that stem from the material’s functionality in the device, including electrical conductivity, chemical reactivity and defects, often pose challenges in the study of the materials by DNP. In this talk I will frame the challenges associated with the application of MAS-DNP to functional materials and describe approaches to address them. Results will be presented from three ubiquitous material systems spanning a range of applications: carbon allotropes, transition metal dichalcogenides (TMDs) and metallic microstructures. We systematically investigated the deleterious effect of materials’ conductivity and formulated means to reduce the effect. We explored the feasibility of utilizing inherent unpaired electrons for endogenous DNP and applied it to probe buried phases in all-solid-state lithium-metal battery and the surface chemistry in carbons. I will show that wealth of information achieved by DNP on various functional materials, can place DNP-NMR as a preferable tool for materials scientists. Our findings are expected to apply to many other systems where functional materials are dominant, making DNP a more general technique.
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    "Adventures in Colloidal Nanocrystal Surface Chemistry"

    Date:
    20
    Wednesday
    July
    2022
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Richard L. Brutchey
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Colloidal nanocrystals possess high surface area-to-volume ratios; as a result ... Read more Colloidal nanocrystals possess high surface area-to-volume ratios; as a result, many nanocrystal properties are heavily influenced by their surfaces. At these surfaces exist a complex interface between the inorganic solid (governed by the crystal structure and particle morphology) and organic ligands. The organic ligands play a key role in controlling nucleation and growth, passivating under-coordinated surface sites, and providing steric stabilization for solvent dispersibility. Depending on the particular application of the nanocrystal, the native organic ligands may then need to be removed or exchanged. We use a complement of NMR spectroscopic techniques to understand the nature of the nanocrystal surface and ligand binding. Then, using principles of inorganic coordination chemistry, we rationally enact ligand exchange reactions on these surfaces to maximize nanocrystal functionality. This talk will briefly discuss the surface chemistry of three different platforms. (1) I will discuss how we experimentally developed an atomistic picture of perovskite nanocrystal surface termination, and then used that information to better understand how common surface treatments can “heal” halide perovskite nanocrystal surfaces. (2) I will discuss how different -donating, L-type ligands were installed on the surface of metal phosphide nanocrystals, and how they affected the hydrogen evolving ability of these electrocatalysts. (3) I will discuss a new strategy for thermally activating metal carbide nanocrystal CO2 reduction catalysts using labile ligands that decompose at significantly lower temperatures than the native ligands. This circumvents issues commonly encountered with high-temperature thermolysis (coking) or acid treatments (etching, poisoning) that are used to activate nanocrystal catalysts.
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    Using functional MRI to better understand neurodevelopmental disorders and to find biomarkers of treatment response in mental illness

    Date:
    05
    Tuesday
    July
    2022
    Lecture / Seminar
    Time: 12:30-13:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Keith Shafritz
    Organizer: Department of Brain Sciences
    Contact: naomi.moses@weizmann.ac.il
    Details: Host: Dr. Michal Ramot michal.ramot@weizmann.ac.il tel:4417
    Abstract: Our ability to correctly diagnose and treat mental illness is limited by the ove ... Read more Our ability to correctly diagnose and treat mental illness is limited by the overlap in symptoms of many disorders, despite differing etiology. Determining the proper course of treatment is quite difficult because treating individual symptoms does not always lead to successful remission and typically involves a trial-and-error approach. Task-based functional MRI has become a highly useful tool for determining the brain regions involved in cognition and behavior in humans, with the potential to be used to find biomarkers of mental illness and treatment outcomes. Much of the research in this domain has focused on the differences in brain activation between groups of individuals with specific mental disorders and typically developing “control” groups. However, by relating brain activation patterns of clinical groups to symptom severity, developmental processes, and response to treatment at the individual level, we can determine brain-based markers that have the potential to be used as diagnostic tools in the future and to determine whether certain treatments would be helpful based on specific brain activation patterns. In this talk, I will present data from studies using task-based functional MRI in autism spectrum disorder, schizophrenia, and childhood adversity that illustrate the potential of this technology for diagnostic and treatment purposes. I will also discuss the promises and limitations of using fMRI as a clinical tool.
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    Multiplexed imaging of endogenous molecular beacons with MRI

    Date:
    09
    Thursday
    June
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Moriel Vandsburger
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Novel treatments that are under development for heart failure, metabolic disorde ... Read more Novel treatments that are under development for heart failure, metabolic disorders, kidney disease, and other debilitating illnesses generally target specific molecular and cellular mechanisms of action. However, assessment of such treatments is often complicated by the lack of easily measurable blood biomarkers, and a reliance upon repeated tissue biopsy. Subsequently, many exploratory studies utilize non-invasive imaging methods to characterize changes in whole organ structure and function as surrogate markers for underlying cellular and molecular changes. Although such measurements can be performed serially, such macro-level imaging measurements are often insensitive to physiologically meaningful treatment responses. In addition, the lack of target specificity represents a fundamental barrier both in pre-clinical development and clinical trials where the information potentially gleaned from a more physiologically rich data set would be of high value to further therapeutic development. My primary research interest is in using magnetic resonance imaging (MRI) as a platform technology for non-invasive and multiplexed molecular imaging in heart and kidney failure. Using a first principles approach, my group seeks to unify changes in myocardial and kidney MRI physics properties with advanced pulse sequence design and analysis in order to enable integrative physiological imaging that both identifies mechanisms of failure earlier than existing diagnostics, and directly measures the impacts of new therapies on their intended therapeutic targets. Using a process of chemical exchange saturation transfer (CEST) we have designed pre-clinical methods to quantify viral carriers of somatic cell gene editing machinery, gene transfer following adeno associated viral gene therapy, and to longitudinally quantify cell survival/proliferation following intra-myocardial implantation in mouse models of regenerative cell therapy. In addition, cardiac CEST approaches for imaging of myocardial creatine and fibrosis using endogenous contrast mechanisms have been translated from mouse models to clinical application in obese adults and renal failure patients on routine hemodialysis. Most recently we have developed methods to probe renal physiology and failure based on endogenous CEST contrast generated by urea. When integrated, these approaches can enable serially non-invasive and multi-scale analysis from the level of gene expression up to whole organ function in disease settings that currently have limited non-invasive molecular tools.
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    New solid-state NMR methods for exciting and separating anisotropic interactions of spin I = 1 nuclei

    Date:
    26
    Thursday
    May
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Rihard Aleksis
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Solid-state NMR has become an essential tool for structural characterisation of ... Read more Solid-state NMR has become an essential tool for structural characterisation of materials, in particular systems with poor crystallinity and structural disorder. In recent years, a surge of interest has been observed for the study of paramagnetic systems, in which the interaction between nuclei and unpaired electrons allows to probe the electronic structure and properties of materials more directly. However, simultaneously this interaction leads to very broad resonances, which are dicult to acquire and interpret. While signi cant advancements in both NMR instrumentation and methodology have paved the way for the study of spin I = 1=2 nuclei in these systems, still many issues remain to be resolved for routine investigation of quadrupolar nuclei I > 1=2. Here we focus on improving both the excitation of the broad resonances and the resolution in the spectra of spin I = 1 nuclei. The latter problem is addressed by developing methods for separation of the shift and the quadrupolar interactions. We introduce two new methods under static conditions, which have the advantage over previous experiments of both suppressing spectral artefacts and exhibiting a broader excitation bandwidth. Furthermore, we demonstrate for the rst time an approach for separation of the anisotropic parts of the shift and quadrupolar interaction under magic-angle spinning. Secondly, to achieve broadband excitation we develop a new theoretical formalism for phase-modulated pulse sequences in rotating solids, which are applicable to nuclear spins with anisotropic interactions substantially larger than the spinning frequency, under conditions where the radio-frequency amplitude is smaller than or comparable to the spinning frequency. We apply the framework to the excitation of double-quantum spectra of 14N and design new pulse schemes with -encoded properties. Finally, we employ the new sequences together with density functional theory calculations to elucidate the electron and hydride ion conduction mechanisms in barium titanium oxyhydride.
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    The awesome power of fluorine NMR - from drugs to cells

    Date:
    12
    Thursday
    May
    2022
    Lecture / Seminar
    Time: 09:30-10:30
    Lecturer: Prof. Angela M. Gronenborn
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Nuclear magnetic resonance (NMR) spectroscopy is a versatile tool for probing st ... Read more Nuclear magnetic resonance (NMR) spectroscopy is a versatile tool for probing structure, dynamics, folding, and interactions at atomic resolution. While naturally occurring magnetically active isotopes, such as 1H, 13C, or 15N, are most commonly used in biomolecular NMR, with 15N and 13C isotopic labeling routinely employed at the present time, 19F is a very attractive and sensitive alternative nucleus, which offers rich information on biomolecules in solution and in the solid state. This presentation will summarize the unique benefits of solution and solid-state 19F NMR spectroscopy for the study of biomolecular systems. Particular focus will be placed on the most recent studies and on unique and important potential applications of fluorine NMR methodology.
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    Magnetic Resonance “Colors”: Design and Implementation in Materials and Life Sciences

    Date:
    25
    Monday
    April
    2022
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Amnon Bar-Shir
    Organizer: Faculty of Chemistry
    Contact: sarah.amzallag@weizmann.ac.il
    Abstract: Luminescent materials with their rich color palettes have revolutionized both sc ... Read more Luminescent materials with their rich color palettes have revolutionized both science and technology through the ability to distinguish between spectrally resolved colors for a wide range of applications from sensing to molecular steganography through high-end electronics and biomedical imaging. Yet, light-based colors suffer from limitations, such as strong scattering and absorbance in opaque media, restricted spectral resolution, photo-bleaching, intolerance for color-palette extendibility and more. Amongst the diverse capabilities and many advantages of Nuclear Magnetic Resonance (spectroscopy and imaging) several are unique, e.g., the sensitivity of the chemical shifts to the chemical environment, the penetrateability of MR signals across opaque objects and the ability to produce three dimensional images of studied subjects. Here, I discuss our recent developments of molecular probes that are capable to generate artificial MR-based colors. To this end, we use synthetic chemistry, nanofabrication, and protein engineering approaches to generate novel molecular formulations (small molecules, nanocrystals (NCs), supramolecular assemblies and proteins) as MRI sensors with unique, advantageous properties (sensitivity, specificity, orthogonality, etc.). I will also discuss how the very same molecular probes can be used to better understand fundamental scientific questions in supramolecular chemistry (e.g., kinetic features of dynamically exchanging molecular systems) and materials science (e.g., understanding and controlling NCs’ formation pathways).
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    Zoom: "Spinning Driven Dynamic Nuclear Polarization with Optical Pumping"

    Date:
    16
    Wednesday
    March
    2022
    Lecture / Seminar
    Time: 15:00-16:00
    Lecturer: Dr. Frederic Mentink-Vigier
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Contact: ana.naamat@weizmann.ac.il
    Details: Zoom link: https://weizmann.zoom.us/j/98720757359?pwd=VEdQUUFXSGRWcUF4U2dBdlQ1 ... Read more Zoom link: https://weizmann.zoom.us/j/98720757359?pwd=VEdQUUFXSGRWcUF4U2dBdlQ1ekxDZz09 Passcode: 039464 We propose a new, more efficient, and potentially cost effective, solid-state nuclear spin hyperpolarization method combining the Cross Effect mechanism and electron spin optical hyperpolarization in rotating solids. We first demonstrate optical hyperpolarization in the solid state at low temperature and low field, and then investigate its field dependence to obtain the optimal condition for high-field electron spin hyperpolarization. The results are then incorporated into advanced Magic Angle Spinning Dynamic Nuclear Polarization (MAS-DNP) numerical simulations that show that optically pumped MAS-DNP could yield breakthrough enhancements at very high magnetic fields. Based on these investigations, enhancements greater than the ratio of electron to nucleus magnetic moments (>658 for 1H) are possible without microwave irradiation. This could solve at once the MAS-DNP performance decrease with increasing field and the high cost of MAS-DNP instruments at very high fields.
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    "Electrified Addition and Subtraction of H2 to Simplify Synthesis"

    Date:
    27
    Sunday
    February
    2022
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Samer Gnaim
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Methodologies that rely on the addition and removal of molecular hydrogen from o ... Read more Methodologies that rely on the addition and removal of molecular hydrogen from organic compounds are one of the most oft-employed transformations in modern organic chemistry, representing a highly relevant tactic in synthesis. Despite their overall simplicity, organic chemists are still pursuing sustainable and scalable processes for such transformations. In this regard, electrochemical techniques have long been heralded for their innate sustainability as efficient methods to perform redox reactions. In our first report, we discovered a new oxidative electrochemical process for the a,b-desaturation of carbonyl functionalities. The described desaturation method introduces a direct pathway to desaturated ketones, esters, lactams and aldehydes simply from the corresponding enol silanes/phosphates, and electricity as the primary reagent. This electrochemically driven desaturation exhibits high functional group tolerance, is easily scalable (1–100 g), and can be predictably implemented into synthetic pathways using experimentally or computationally derived NMR shifts. Our second report demonstrated the reductive electrochemical cobalt-hydride generation for synthetic organic applications inspired by the well-established cobalt-catalyzed hydrogen evolution chemistry. We have developed a silane- and peroxide-free electrochemical cobalthydride generation for formal hydrogen atom transfer reactions reliant on the combination of a simple proton source and electricity as the hydride surrogate. Thus, a versatile range of tunable reactivities involving alkenes and alkynes can be realized with unmatched efficiency and chemoselectivity, such as isomerization, selective E/Z alkyne reduction, hydroarylation, hydropyridination, strained ring expansion, and hydro-Giese.
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    Ph.D thesis defense:" Advancing the optimally-tuned range-separated hybrid approach"

    Date:
    13
    Sunday
    February
    2022
    Lecture / Seminar
    Time: 16:00-17:00
    Lecturer: Georgia Prokopiou
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: Zoom Link: https://weizmann.zoom.us/j/95952232097?pwd=OW9SL2JlNkNYQVJ1cW5FT05H ... Read more Zoom Link: https://weizmann.zoom.us/j/95952232097?pwd=OW9SL2JlNkNYQVJ1cW5FT05HcEh2QT09 The optimally-tuned range separated hybrid (OT-RSH) functional is a non-empirical method within density functional theory, which is known to yield accurate fundamental gaps for a variety of systems. Here we extend its applicability to magnetic resonance parameters, enhance its accuracy by designing OT-RSH based double-hybrid functionals, and increase its precision for solid-state calculations by designing and generating RSH pseudopotentials.
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    Zoom: M.Sc thesis defense: "Investigation of the ceramic – polymer interface in composite solid electrolyte by Nuclear Magnetic Resonance Spectroscopy"

    Date:
    30
    Sunday
    January
    2022
    Lecture / Seminar
    Time: 13:00-14:00
    Lecturer: Chen Oppenheim
    Organizer: Department of Molecular Chemistry and Materials Science
    Contact: ana.naamat@weizmann.ac.il
    Abstract: https://weizmann.zoom.us/j/97328767376?pwd=MkZoQ0hmbVVRank0bzkxbGpqSUdYUT09 pas ... Read more https://weizmann.zoom.us/j/97328767376?pwd=MkZoQ0hmbVVRank0bzkxbGpqSUdYUT09 passcode: 891716 Lithium-ion batteries with liquid electrolytes are commonly employed for powering portable electronic devices. To expand the range of applications where Li ions batteries can be used (e.g., electric transportation), solid electrolytes are considered as a safer alternative to the liquid electrolytes and they may enable use of lithium metal anodes. In this study we focused on composite solid electrolytes which are based on solid polymer (Polyethylene Oxide) and ceramic particles (Li1.5Al0.5Ge1.5P3O12, LAGP). Previous studies revealed that the highest ionic conduction path in the composites is through the interface polymer - ceramic interface. However, the chemical nature of the interface and the reason for its higher conductivity remains unclear. We aim to gain molecular - atomic level insight into the nature of the polymer - ceramic interface from solid state NMR spectroscopy. Here, I will present the development of a solid - state NMR approach that can potentially be used to selectively probe the interface. To gain sensitivity and selectivity Dynamic Nuclear Polarization (DNP), a process in which high polarization from unpaired electrons is transferred to surrounding nuclear spins will be employed. Several metal ion dopants were tested for their DNP performance in LAGP powder, and Mn2+ ions were further examined in their efficacy in the composite electrolyte. The approach was tested for selectively enhancing the NMR signal of the PEO - LAGP interface. Electrochemical characterization and in - depth solid state NMR studies provided insight into the performance of the composite and degradation processes in the composite.
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