Upcoming

All upcoming events

Zoom: “Fast, accessible hyperpolarization for MRI and liquid-state NMR”

Date:
28
Thursday
October
2021
Lecture / Seminar
Time: 09:30-10:30
Lecturer: Ilai Schwartz
Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
Details: .
Abstract: Zoom Lecture: Zoom: : https://weizmann.zoom.us/j/92362836861?pwd=Q29EMVcxaXJ ... Read more Zoom Lecture: Zoom: : https://weizmann.zoom.us/j/92362836861?pwd=Q29EMVcxaXJkSE5QbWxpUEdPdGNQUT09 Passcode: 526083 Nuclear spin hyperpolarization provides a promising route to overcome the challenges imposed by the limited sensitivity of nuclear magnetic resonance. Significant progress in the last decades was achieved by the development of new hyperpolarization techniques (e.g. dissolution-DNP). This has resulted in the demonstration of new MRI applications utilizing hyperpolarized 13C nuclei in metabolic probes as well as promising results in hyperpolarized liquid state NMR. However, hyperpolarization for both MRI and liquid state NMR applications is still a challenging endeavor, requiring expensive hardware and imposing limitations on the experimental setup. In this talk I will present our latest developments for achieving fast, accessible polarization for both MRI and NMR applications utilizing a variety of polarization techniques: (1) For MRI applications we have demonstrated for the first time that using parahydrogen induced polarization (PHIP), hyperpolarized fumarate and pyruvate can be prepared at clinically relevant concentrations (> 100mM) and hyperpolarization values up to 20% at the time of injection. In a comparative study we show that PHIP based methods can compete and even surpass both polarization and concentration levels of metabolic tracers prepared by DNP but at a fraction of the cost, complexity and preparation time. (2) Leveraging optical polarization, we developed a technique for versatile liquid state NMR hyperpolarization, achieving between 200- and 1730-fold signal enhancement at 1.45T for a range of small molecules. The signal enhancement is induced by using optically polarized pentacene-doped naphthalene crystals as a source of spin polarization. We demonstrate that rapid dissolution of the highly polarized crystal enables transfer of polarization to the target molecules via intermolecular cross relaxation in the liquid state at room temperature. Due to the extremely high magnetization of the naphthalene molecules, the cross relaxation leads to a substantial polarization buildup in the target analytes. Crucially, the polarization transfer is achieved without costly instrumentation and occurs in less than a minute inside the NMR spectrometer
Close abstract

    Past

    All Events

    The interaction of valence and information gain during learning, perception and decision-making

    Date:
    27
    Thursday
    May
    2021
    Lecture / Seminar
    Time: 11:00-12:30
    Lecturer: Ido Toren (PhD Thesis Defense)
    Organizer: Department of Brain Sciences
    Details: Neurobiology Students & Postdocs Seminar Zoom link to join: https://weizmann. ... Read more Neurobiology Students & Postdocs Seminar Zoom link to join: https://weizmann.zoom.us/j/92234357805?pwd=aVkrR21CSUVtVS9tSEJYRDkwOFRidz09 Meeting ID: 922 3435 7805 Password: 648092
    Close details
    Abstract: Decision making is a fundamental ability to human life. Even the simplest decisi ... Read more Decision making is a fundamental ability to human life. Even the simplest decision we make requires integration of multiple factors in our brain, such as prior knowledge, information from the environment, emotions and many more. Despite many years of research and numerous important and ground-breaking findings on how learning and decision-making are generated in our brain, a lot of knowledge is still required for a comprehensive understanding of it. My research initiated from the motivation to understand the unique contribution of valence (rewards and punishments) – when presented as feedback during learning – to perception and decision-making. For that purpose, I studied multiple groups of individuals under different experimental conditions created to elucidate behavioral and neural responses to rewards and punishments. I asked how prediction errors (PE, the difference between expected and received outcomes) bias the perception of time, and how valence and information from feedback, factors that are often indistinguishable, differently guide decision making in a multi-choice environment. Using functional MRI and computational models, I found that positive and negative PEs, known to drive learning, bias the perception of time in opposite directions. Positive PEs induce change in the perceived time so it seems longer compared to a neutral condition (no PE). In contrast, when a negative PE is detected, time is perceived to be shorter. My results identify the Putamen, a structure that receives dopaminergic projections and is involved in time perception, as the brain region that likely drives this bias and underlies the interaction between time perception and prediction-errors. In addition, I demonstrated that knowing the outcome valence in advance can enable an information-based decision making, namely one that is not affected by the valence itself and is driven only by the information available in the environment. Because uncertainty regarding choice increases when more options are available to choose from, a ‘right’ feedback provides more information to the learning process, compared to a ‘wrong’ feedback. This was accompanied by a differential activation in the ACC, PFC and striatum. Importantly, in this context, punishment avoidance is equally rewarding, and indeed I found that choice behavior and the neural networks underlying choice and feedback processing are similar in the two scenarios – for punishments and rewards. Overall, my work develops and suggests computational and neural mechanisms for specific roles of the information carried by prediction-errors. These findings can enhance our understanding of the fundamental roles of valence and information gain during learning and decision making. Zoom link to join: https://weizmann.zoom.us/j/92234357805?pwd=aVkrR21CSUVtVS9tSEJYRDkwOFRidz09 Meeting ID: 922 3435 7805 Password: 648092
    Close abstract

    Zoom Lecture: “NMR of RNA: dynamics or in-cells”

    Date:
    06
    Thursday
    May
    2021
    Lecture / Seminar
    Time: 09:15-10:15
    Lecturer: Prof. Katja Petzold
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Zoom Lecture: https://weizmann.zoom.us/j/98819686427?pwd=algvMEJUNHdvaFppNS9x ... Read more Zoom Lecture: https://weizmann.zoom.us/j/98819686427?pwd=algvMEJUNHdvaFppNS9xVzlTUkhYQT09 Passcode: 551107 Many functions of RNA depend on rearrangements in secondary structure that are triggered by external factors, such as protein or small molecule binding. These transitions can feature on one hand localized structural changes in base-pairs or can be presented by a change in chemical identity of e.g. a nucleo-base tautomer. We use and develop R1ρ-relaxation-dispersion NMR methods for characterizing transient structures of RNA that exist in low abundance (populations
    Close abstract

    Using Ultra-High Field MRI to Study the Human Brain

    Date:
    04
    Thursday
    March
    2021
    Lecture / Seminar
    Time: 09:00-10:00
    Location: ZOOM
    Lecturer: Dr. Edna Furman-Haran and Dr. Tali Weiss
    Organizer: Department of Life Sciences Core Facilities

    “Low-field MRI: new perspectives”

    Date:
    28
    Thursday
    January
    2021
    Lecture / Seminar
    Time: 09:30-10:30
    Lecturer: Prof. Najat Salameh
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Zoom: Link: https://weizmann.zoom.us/j/98957854014?pwd=ZTEyazd6cThxUE90L3ZJbkdkb ... Read more Zoom: Link: https://weizmann.zoom.us/j/98957854014?pwd=ZTEyazd6cThxUE90L3ZJbkdkbkFWQT09 passcode: 159170 Magnetic Resonance Imaging (MRI) is a non-ionizing, non-invasive imaging modality that has become key in modern medicine. Its high value resides in a broad range of soft tissue contrasts or biomarkers that can be tuned to enable the identification and follow-up of many pathophysiological or metabolic processes. Such developments were made possible thanks to almost forty years of hardware and software development, yet access to MRI nowadays remains exclusive, bound to radiology suites in hospitals, and restricted to less than half of the world population. This limited accessibility is mostly due to its one-fits-all design and its prerequisites for intense magnetic field strength that impact cost, siting infrastructure, and clinical compatibility. One way to improve accessibility in MRI is to lower the magnetic field strength that will naturally influence cost, siting, and compatibility. Further, lowering the field strength can translate in smaller footprint designs which geometry and contrast could purposely be tuned to certain targeted applications. Indeed, relaxation mechanisms are known to change with the surrounding magnetic field, with larger T1 dispersion at low field that have for the most part been unexplored. Although very promising, many challenges arise linked to the lower intrinsic nuclear spin polarization inherent to low field technologies, calling for original and innovative approaches to reach clinical relevance. During this seminar, Prof. Najat Salameh will describe those challenges and possible solutions by presenting the current landscape of low field imaging and recent progress made at the Center for Adaptable MRI Technology, Basel University.
    Close abstract

    Diffusion properties of intracellular metabolites: compartment specific probes for cell structure and physiology

    Date:
    05
    Tuesday
    January
    2021
    Lecture / Seminar
    Time: 12:30-13:30
    Lecturer: Prof. Itamar Ronen
    Organizer: Department of Brain Sciences
    Details: Zoom link to join: https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laU ... Read more Zoom link to join: https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laUUdGbWR1VFJTdz09 Meeting ID: 966 0803 3618 Password: 564068 Host: Dr. Rita Schmidt rita.schmidt@weizmann.ac.il tel: 9070
    Close details
    Abstract: Diffusion weighted MRI (DWI) is the main neuroimaging modality used in non-invas ... Read more Diffusion weighted MRI (DWI) is the main neuroimaging modality used in non-invasive investigations of tissue microstructure, and provides quantitative cytomorphological information on a spatial scale well below the nominal resolution of MRI. The main limitation of DWI is its lack of compartmental specificity, as its “reporter molecule” is water, ubiquitous in all tissue compartments and cell types. Brain metabolites are mostly confined to the intracellular space, and their concentrations vary across cell types. Several metabolites give rise to quantifiable magnetic resonance spectroscopy (MRS) signatures, and are thus considered as compartment-specific and sometimes cell-specific markers. Sensitization of MRS to diffusion results in a set of diffusion properties for a variety of intracellular metabolites, from which microstructural information specific to the intracellular space can be obtained. A proper choice of experimental settings can be used to investigate properties that range from cytoplasmic viscosity and tortuosity of the intracellular space, to overall cell morphological features. The specificity of some metabolites to different cell types such as neurons and astrocytes opens the way to studying morphological properties of different cell populations and monitoring their modulation by physiological changes in health and disease. The presentation will introduce methodological concepts of diffusion-weighted MRS, followed by simple examples that demonstrate the unique ability of diffusion-weighted MRS to characterize cell-type specific structural features. Special emphasis will be bestowed on experimental and modelling frameworks that merge the specificity of diffusion-weighted MRS with the sensitivity of DWI to gain insights on tissue microstructure beyond what each method can separately provide. Zoom link to join:https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laUUdGbWR1VFJTdz09 Meeting ID: 966 0803 3618 Password: 564068 Host: Dr. Rita Schmidt rita.schmidt@weizmann.ac.il tel: 9070
    Close abstract

    1H LF NMR Sensor Application for Monitoring of PUFA-rich Healthy Food Autoxidation

    Date:
    31
    Thursday
    December
    2020
    Lecture / Seminar
    Time: 09:30-10:30
    Lecturer: Prof. Zeev Wiesman
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Abstract: The present seminar will review our work in 1H LF NMR energy relaxatio ... Read more Abstract: The present seminar will review our work in 1H LF NMR energy relaxation time technology and its application in chemical and morphological characterization and monitoring of oxidation of polyunsaturated fatty acids (PUFA) found in many important commercial products such as edible oils, foods, and biological systems. PUFA’s aggregates are related simultaneously with material’s functionality and degradation. The multiple double bonds and allylic carbons characteristics of the PUFA’s molecular structure are responsible for its oxidation susceptibility and can result in the degrade of the product’s functionality and formation of toxic substances. Wherein individual PUFA molecules have specific structures their material functionality and stability against oxidation are strongly depended on their aggregate structures such as in oils or within aqueous emulsions and specific arrangements within these structures with other components such as antioxidants is an important material parameter. The oxidation degree of PUFA’s rich materials can be measured via different methods such as volumetric, spectroscopic and chromatographic technologies. The traditional technologies based on titrimetric techniques have many drawbacks. These methods need strict time regimes during individual stages of analyzes, control of the intensity of the agitation and control of reaction components including light and atmospheric oxygen exposure. Other disadvantage of these traditional methodologies is the requirement of a large amount of solvents, being environmental unfriendly. In order to overcome the disadvantages of the traditional technologies used to monitor oxidation we are suggesting the use 1H LF NMR relaxation. This technology does not require organic solvents, complex samples preparation and the sample is preserved after analysis. The 1H LF NMR generates 2D T1 (spin-lattice) vs. T2 (spin-spin) energy relaxation time domain that is able together with self-diffusion test to characterize chemical and morphologically complex aggregate materials such as PUFA in liquid or solid assembly or in presence of interfacial forces of water. In addition, these spectra can efficiently monitor oxidation and assess antioxidants efficacy. We demonstrate the work we have done to date on the 1H LF NMR data processing optimization and the application of this technology in the characterization and monitoring of oxidation on oils on fatty acids saturated, monounsaturated and polyunsaturated. This sensor application is of relevant contributions for diverse fields such as food industries, pharmaceuticals, cosmetics and biofuels. The seminar is divided into three parts: a) Optimization of the ILT data processing technology of 1H LF NMR energy relaxation time. This study showed the efficiency of the regularization parameters for data reconstruction, and a relative high accuracy of the primal dual convex objectives (PDCO) solutions in comparison to the graphic results of real data. b) Developing of intelligent NMR relaxation sensor applications of fatty acids (FA) with saturated chains, MUFA and PUFA-rich oils for their chemical and physical/morphological characterization and monitoring of their autoxidation. Detailed fingerprinting chemical and morphological maps were generated for saturated FAs, MUFAs, PUFAs and their oxidation polymerized final products. It was possible to propose peak assignments to the various spin-lattice (T1) and spin –spin (T2) energy relaxation time proton populations (TD) based on the molecular segmental motions of the different fatty acids chemical and structural segments (e.g., glycerol; double bonds; aliphatic chains; and tails) to generate an explicatory dictionary of T1 and T2 values with chemical and physical/morphological structures and their changes due to oxidation. c) Developing of intelligent 1H LF NMR energy relaxation time domain sensor application for PUFA-rich oil-in-water emulsions characterization and monitoring autoxidation. Emulsions based on linseeds, very rich in α-linolenic acid PUFA (18:3) and structural oleosin protein and other emulsification agents naturally producing nano-scale oxidation stable oil bodies, were formed from linseed in water. The linseed emulsions enriched with PUFA-rich fish oil were analyzed under thermal oxidation conditions, using 1H LF NMR T1-T2 energy relaxation time reconstruction for determining the oil bodies composition and structure and oxidative stability.
    Close abstract

    Zoom lecture: Quantum sensor assisted magnetic resonance

    Date:
    15
    Thursday
    October
    2020
    Lecture / Seminar
    Time: 09:30-10:30
    Lecturer: Prof. Ashok Ajoy
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Details: Yeda Research and Development Ltd. is the commercial branch of the Weizmann Inst ... Read more Yeda Research and Development Ltd. is the commercial branch of the Weizmann Institute of Science. Yeda holds an exclusive right to commercialize the unique intellectual property developed by the scientists at the Weizmann Institute.
    Close details
    Abstract: Nuclear magnetic resonance (NMR) spectroscopy, is renowned for its high chemic ... Read more Nuclear magnetic resonance (NMR) spectroscopy, is renowned for its high chemical specificity, but suffers from low sensitivity and poor spatial resolution. This has largely locked up NMR in “central facilities”, where the measurement paradigm involves taking the sample to the NMR spectrometer. We are innovating a class of optical NMR probes that can allow one to invert this paradigm, effectively bringing the NMR spectrometer into the sample. This would open possibilities for NMR probes of analytes in their local environment. These “deployable” NMR sensors rely on a uniquely optically addressable spin platform constructed out of nanoparticles of diamonds, hosting defect centers (NV centers) and 13C nuclei. Such electron-nuclear spin hybrids serve dual-roles as optical “polarization injectors” and optical NMR detectors while also being targetable to within the sample of interest. I will focus on the main ingredients of this technology, while alluding to potential frontier applications opened as a result. Zoom link: https://weizmann.zoom.us/j/98496818322?pwd=RW03TWtTUUpKYXBXQlJtbnprMTRKdz09 passcode: 888482
    Close abstract

    ClearSight™: A portable system that uses diffusion NMR to probe the margins of excised tumors

    Date:
    16
    Thursday
    July
    2020
    Lecture / Seminar
    Time: 09:30-10:30
    Lecturer: Dr. Saul Stokar
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Abstract: Zoom link: https://weizmann.zoom.us/j/91154950215?pwd=ZkRsTWJzL1AzMWpNbFVSVUF4d0 ... Read more Zoom link: https://weizmann.zoom.us/j/91154950215?pwd=ZkRsTWJzL1AzMWpNbFVSVUF4d05zQT09 Password: 388848 Diffusion NMR weighted NMR and MRI are very powerful techniques for investigating microscopic details about tissue architecture, either normal or in a diseased state. In addition to its traditional use in diagnosing stroke and ischemic injury in the brain, in recent years DWI has been used to diagnose various kinds of cancer, including breast, prostate and lung cancers. In this seminar we will present an overview of a novel portable system that uses DWI to check whether the margins of excised breast tumors are tumor-free. This is extremely important both for the patient and the hospital, since it obviates the need to perform additional surgery if the subsequent pathology indicates the presence of tumor on the margin of the excised tissue, something that occurs today in up to 25% of breast-conserving surgeries. We shall provide an overview of diffusion MRI, the unique challenges of performing MRI in or near the operating theater, the architecture of ClearCut's system, computer simulations of its performance and an overview of the clinical results obtained to date.
    Close abstract

    Sparsity-based Methods for Rapid MRI

    Date:
    25
    Thursday
    June
    2020
    Lecture / Seminar
    Time: 09:30-10:30
    Lecturer: Dr. Efrat Shimron
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Abstract: Zoom Lecture: https://weizmann.zoom.us/j/99058507421 Magnetic Resonance Ima ... Read more Zoom Lecture: https://weizmann.zoom.us/j/99058507421 Magnetic Resonance Imaging (MRI) is a superb imaging modality that provides high-quality images of the human body. However, one of its major limitations is the long acquisition time, which hinders the MRI clinical use. The acquisition time can be shortened by acquiring less data; however, this requires suitable methods for accurate image reconstruction from subsampled data, which is acquired with a sub-Nyquist rate. In this seminar, four novel methods for image reconstruction from subsampled data will be presented. These methods build upon the well-established frameworks of Parallel Imaging (PI) and Compressed Sensing (CS), utilize a-priori knowledge about data sparsity, and address current limitations of PI-CS methods. The first two methods accelerate static MRI scans by introducing the Convolution-based Reconstruction (CORE) framework, which offers a parameter-free non-iterative reconstruction. Experiments with in-vivo 7T brain data demonstrated that these methods perform comparably to the well-established GRAPPA and l1-SPIRiT methods, with the advantage of shorter computation times and reduced need for parameter calibration. The next two developed methods accelerate dynamic MRI scans that provide temperature monitoring in High Intensity Focused Ultrasound (MRgHIFU) thermal ablation treatments. The developed methods enable rapid MR monitoring by reconstructing temperature changes from subsampled data. Validation experiments were performed with in-vivo data from clinical treatments of prostate cancer in humans; these showed that the proposed methods significantly outperform two state-of-the-art methods in the temperature reconstruction task
    Close abstract

    Real Time Quantum Sensing and Jüdisch-Deutsch

    Date:
    18
    Thursday
    June
    2020
    Lecture / Seminar
    Time: 09:30-10:30
    Lecturer: Dr. Amit Finkler
    Organizer: Clore Institute for High-Field Magnetic Resonance Imaging and Spectroscopy
    Abstract: Zoom Lecture: Link: https://weizmann.zoom.us/j/98578269625 Magnetometry on ... Read more Zoom Lecture: Link: https://weizmann.zoom.us/j/98578269625 Magnetometry on the nanoscale range stands to benefit from quantum-enhanced sensing techniques, as these can potentially overcome classical noise limits. Specifically in our group we use a single nitrogen-vacancy center as an atomic-sized quantum sensor, with uT(nT) magnetic field sensitivity for dc(ac) fields. Yet our measurement technique does rely on classical averaging due to a relatively poor signal-to-noise ratio. In this respect, a real-time response and feedback during signal acquisition based on (quantum) phase estimation promises to significantly reduce averaging time by using prior information obtained during the measurement. I will present our current efforts in this direction, with the aim of performing adaptive sensing of nanoscale magnetic fields. Both static (dc) and dynamic (ac) problems will be addressed. Finally, since this is after all a magnetic resonance seminar, I will present the relevant research context pertaining to electron spin resonance of small molecules and explain how we intend to reach the single molecule limit with this quantum sensing technology.
    Close abstract

    From Cognition to Depression: Using Magnetic Resonance Spectroscopy to Study In-vivo Neurochemistry

    Date:
    03
    Tuesday
    March
    2020
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Assaf Tal
    Organizer: Department of Brain Sciences
    Details: Host: Dr. Meital Oren meital.oren@weizmann.ac.il tel: 6479 For assistance wit ... Read more Host: Dr. Meital Oren meital.oren@weizmann.ac.il tel: 6479 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Close details
    Abstract: Magnetic Resonance Spectroscopy (MRS) can be used to measure the in-vivo concent ... Read more Magnetic Resonance Spectroscopy (MRS) can be used to measure the in-vivo concentrations of several metabolites in the brain non-invasively. I will present our work using MRS to study two aspects of brain metabolism. First, I'll talk about our work on functional MRS, whereby we look at neurochemical changes during or after learning or function. In the second half of the talk, I will focus on new methods we're developing in the lab, and in particular on our ability to measure the thermal relaxation times of metabolites, which probe specific cellular and subcellular microenvironments. I will present some preliminary data showing where and how this could be useful.
    Close abstract

    Chemical Biology Seminar Series

    Date:
    27
    Thursday
    February
    2020
    Lecture / Seminar
    Time: 14:00-15:00
    Title: In Vivo Chemical Probes for MRI and Fluorescence Imaging
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Kazuya Kikuchi
    Organizer: The Dr. Barry Sherman Institute for Medicinal Chemistry

    Ultra-High Field Nuclear Magnetic Resonance

    Date:
    25
    Tuesday
    February
    2020
    -
    26
    Wednesday
    February
    2020
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre

    Whole-brain fMRI of the Behaving Mouse

    Date:
    04
    Tuesday
    February
    2020
    Lecture / Seminar
    Time: 12:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Itamar Kahn
    Organizer: Department of Brain Sciences
    Details: Host: Dr. Meital Oren meital.oren@weizmann.ac.il tel: 6479 For assistance wit ... Read more Host: Dr. Meital Oren meital.oren@weizmann.ac.il tel: 6479 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Close details
    Abstract: Functional MRI is used pervasively in human brain research, enabling characteriz ... Read more Functional MRI is used pervasively in human brain research, enabling characterization of distributed brain activity underlying complex perceptual and cognitive processes. However, heretofore this technique has been limited in utility in rodents. I will present whole-brain functional imaging of head-fixed mice performing go/no-go odor discrimination in a platform allowing precise odor-delivery system, non-invasive sniff recordings and lick detection, detailing the brain regions subserving this behavior from the naïve state to task proficiency including learning of rule reversal. I will briefly discuss efforts to expand the mouse fMRI platform to additional modalities and conclude by describing the prospects of this approach more broadly.
    Close abstract

    Solid State NMR of low abundant quadrupolar nuclei achieved through extended coherence lifetimes

    Date:
    16
    Thursday
    January
    2020
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Daniel Jardon-Alvarez
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Less is more! By using extremely low power refocusing π pulses in echo train se ... Read more Less is more! By using extremely low power refocusing π pulses in echo train sequences the coherence lifetime, T2, of the central transition of half-integer quadrupolar nuclei can be largely extended. This effect is particularly impactful in systems dilute in NMR active nuclei, where sources of decoherence are scarce. Crucial to this lifetime extension is the avoidance of coherence transfer to short-lived non-symmetric “killing” transitions. For 17O in polycrystalline α-quartz we were able to retain coherent magnetization for over four minutes on the transverse plane. This translates into enormous sensitivity gains for echo train acquisition after addition of the long living echoes. By combining satellite population transfer schemes with a low power CPMG on 17O in quartz, we obtain over a 1000-fold sensitivity enhancement compared to a spectrum from a free induction decay acquired at a more typical rf field strength. This enhancement allows the acquisition of a highly resolved 17O spectrum within less than one hour, despite its low natural abundance and a spin-lattice relaxation time of approximately 900 s. In this talk I will present a thorough analysis of the effects of pulse power on the echo intensity, coherence lifetime and line shape integrity. Finally, we apply this approach on various crystalline and glassy inorganic solids, including other low sensitivity nuclei, such as 33S and 45Ca, showing that it can be beneficial for a large number of systems.
    Close abstract

    New Approaches for Structure Determination of Protein Complexes by Mass Spectrometry

    Date:
    13
    Monday
    January
    2020
    Colloquium
    Time: 11:00-12:15
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Vicki Wysocki
    Organizer: Faculty of Chemistry
    Abstract: Characterization of the overall topology and inter-subunit contacts of protein c ... Read more Characterization of the overall topology and inter-subunit contacts of protein complexes, and their assembly/disassembly and unfolding pathways, is critical because protein complexes regulate key biological processes, including processes important in understanding and controlling disease. Tools to address structural biology problems continue to improve. Native mass spectrometry (nMS) and associated technologies such as ion mobility are becoming an increasingly important component of the structural biology toolbox. When the mass spectrometry approach is used early or mid-course in a structural characterization project, it can provide answers quickly using small sample amounts and samples that are not fully purified. Integration of sample preparation/purification with effective dissociation methods (e.g., surface-induced dissociation), ion mobility, and computational approaches provide a MS workflow that can be enabling in biochemical, synthetic biology, and systems biology approaches. Native MS can determine whether the complex of interest exists in a single or in multiple oligomeric states and can provide characterization of topology/intersubunit connectivity, and other structural features. Beyond its strengths as a stand-alone tool, nMS can also guide and/or be integrated with other structural biology approaches such as NMR, X-ray crystallography, and cryoEM.
    Close abstract

    NMR structure and dynamics studies of oligo- and polysaccharides

    Date:
    30
    Monday
    December
    2019
    Lecture / Seminar
    Time: 09:00-10:00
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Daron Freedberg
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Glycans are ubiquitous in nature and participate in a wide variety of biological ... Read more Glycans are ubiquitous in nature and participate in a wide variety of biological processes, that span from mediating cell-cell interactions to modulating protein stability and folding. Glycan involvement in diverse biological functions can be rationalized by the equally extensive potential for structural diversity. They vary not only in monosaccharide composition and primary sequence, like proteins and nucleic acids, but also the monosaccharides can vary in ring sizes, linkage types, and functional group modifications. Therefore, their structural complexity has the potential for encoding a myriad of functions. However, it is this “structural richness” that hampers progress in stablishing structure-function relationships, simply because tools and strategies for structure determination are lacking. We are delineating three-dimensional glycan solution structure to gain insight into how they function, which should facilitate development of glycan-based vaccines, drug delivery systems, and antibiotics of the future. To this end, we use heteronuclear multidimensional NMR to determine conformations and dynamics of 15N, 13C enriched oligo- and polysaccharides. We have detected interresidue hydrogen bonds and used RDCs to delineate the relative orientations of the rigid monosaccharide building blocks. However, RDC measurements are fraught with errors from strong coupling effects. Thus, we have developed methods to accurately measure one-bond 1H-13C splittings and 13C-13C splittings as well as RDCs. I will illustrate the application of these methods for bacterial polysaccharide model systems and show how we applied them to support the two-residue per turn helical structure of 2-8 tetrasialic acid and the smaller conformationally stable dimer in solution at low temperatures.
    Close abstract

    Simulating the whole of magnetic resonance

    Date:
    19
    Thursday
    December
    2019
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Ilia Kuprov
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: In a couple of years from now, we will finish kernel programming for Spinach – ... Read more In a couple of years from now, we will finish kernel programming for Spinach – a spin dynamics simulation library that supports all types of magnetic resonance spectroscopy, from Gd3+ DEER, through DNP and NMR, and all the way to singlet state diffusion MRI, including chemical kinetics, optimal control, and advanced relaxation theories. This level of generality hinges on: 1. The ability to treat classical degrees of freedom (diffusion, hydrodynamics, radiofrequency and microwave phases, stochastic tumbling, etc.) at the same conceptual level as spin degrees of freedom – the corresponding classical equations of motion must be integrated into the density matrix formalism. 2. The ability to survive enormous Kronecker products. A well digitised medical phantom would have at least a hundred points in each of the three directions, meaning a dimension of at least 1003 = 106 for the spatial dynamics generator matrices. At the same time, a typical radical contains upwards of ten coupled spins, meaning a Liouville space dimension of at least 410. Direct products of spin and spatial dynamics generators would then have the dimension in excess of 1012 even before chemical kinetics is considered. 3. Code parallelisation over cluster architectures, including the possibility of using a GPU on each node of the cluster. The principal problem is parallelisation mode switching between powder averages, indirect dimensions of pulse sequences, frequency points of frequency domain simulations, etc. – each simulation type would in general require a different mode of parallelisation and GPU utilisation. This report is about solving all of this, and on where the dark art of simulating a time-domain magnetic resonance experiment stands at the moment. Two recent innovations are the abandonment of Liouville equation in favour of Fokker-Planck equation as the core formalism, and the use of tensor structured objects that never open Kronecker products. A separate story is recent GPUs: NVidia Tesla V100 performs ~1013 double-precision multiplications per second – an astounding amount of computing power that is surprisingly easy to use.
    Close abstract

    In vivo multimodality imaging of immune-vascular interactions in cardiovascular disease

    Date:
    12
    Thursday
    December
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Katrien Vandoorne
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Cardiovascular disease is a result of genetic and environmental risk factors tha ... Read more Cardiovascular disease is a result of genetic and environmental risk factors that together generate arterial and cardiac pathologies. Blood vessels connect multiple organ systems throughout the entire body allowing organs to interact via circulating messengers. Multimodality imaging achieves integration of these interfacing systems’ distinct processes, quantifying interactions that contribute to cardiovascular disease. Noninvasive multimodality imaging techniques are emerging tools that can further our understanding of this complex and dynamic interplay. Multichannel multimodality imaging including optics, CT, PET and MRI, are particularly promising because they can simultaneously sample multiple biomarkers. As the opportunities provided by imaging expand, mapping interconnected systems will help us decipher the complexity of cardiovascular disease and monitor novel therapeutic strategies.
    Close abstract

    Augmented methods for measuring one-bond heteronuclear spin pairs over a wide range of MAS frequencies

    Date:
    05
    Thursday
    December
    2019
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Dr. Mukul Jain
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Measuring quantitative distances are important for studying the structural pro ... Read more Measuring quantitative distances are important for studying the structural properties of molecules at an atomic scale. Dipole-dipole coupling encodes for distance information between spin pairs. Additionally, the anisotropy of dipole-dipole coupling is also very sensitive to the sub-microsecond dynamics occurring in the molecules, and therefore can be used to estimate it. Rotational Echo Double Resonance (REDOR) and Correlation of Dipolar coupling and Chemical shift (DIPSHIFT) experiments are the most preferred experiments for measuring distances between a heteronuclear spin pair using Magic angle spinning (MAS) solid-state NMR. But these experiments can be used only for a small range of coupling strengths depending on the MAS frequency of the experiment. In the talk, I will discuss the latest developments we have made for measuring a wide range of coupling strengths using REDOR over a wide range of MAS frequencies. Further, I will also show that REDOR and DIPSHIFT are different realizations of a same experiment and this unification comes naturally out of our augmented REDOR sequence. Further, I will discuss a method to perform REDOR experiments with low radiofrequency amplitude pulses at MAS frequencies larger than 80~kHz. This method extends the application of REDOR and DIPSHIFT at very fast MAS frequencies, where the radiofrequency amplitude requirement becomes too high for nuclei other than 1H. Overall, the methods discussed here allow for measuring dipole-dipole coupling between heteronuclear spin-pairs over a wider range of MAS frequencies. References: 1. T. Gullion and J. Schaefer, Journal of Magnetic Resonance, 1989. 2. M. G. Munowitz et al., Journal of American Chemical Society, 1981. 3. M. Hong et al., Journal of Magnetic Resonance, 1997. 4. P. Schanda et al., Journal of Magnetic Resonance, 2019. 5. M. G. Jain et al., Journal of Chemical Physics, 2017. 6. M. G. Jain et al., Journal of Chemical Physics, 2019. 7. M. G. Jain et al., Journal of Magnetic Resonance, 2019.
    Close abstract

    Bio-structural insights from solid state NMR: The small (Lithium) and the large (Phage)

    Date:
    12
    Tuesday
    November
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Helen and Milton A. Kimmelman Building
    Lecturer: Prof. Amir Goldbourt
    Organizer: Department of Chemical and Structural Biology

    How Metal Ions in the Brain Tip the Toxic Balance of the Killer Prion Protein: Insights from NMR and EPR”

    Date:
    07
    Thursday
    November
    2019
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Prof. Glenn L. Millhauser
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: A prion is a misfolded form of the cellular prion protein, PrPC. Although the ro ... Read more A prion is a misfolded form of the cellular prion protein, PrPC. Although the role of PrP in neurodegeneration was established over 30 years ago, there is little understanding of the protein’s normal function, and how misfolding leads to profound disease. Recent work shows that PrPC coordinates the cofactors Cu2+ and Zn2+, and regulates the distribution of these essential metal ions in the brain. Moreover, these metals stabilize a previously unseen fold in PrPC, the observation of which provides new insight into the mechanism of prion disease. To date, Cu2+ coordination was thought to be limited to residues within the protein’s N-terminal domain. However, new NMR and EPR experiments suggest that histidine residues in the C-terminal domain assist in stabilizing the Cu2+-promoted PrPC fold. This talk will describe combined NMR, EPR, mutagenesis and physiological studies that provide new insight into the PrPC fold and function.
    Close abstract

    Characterization of Biomolecule and Structure Changes using Polarization Transfer from Hyperpolarized Water

    Date:
    31
    Thursday
    October
    2019
    Lecture / Seminar
    Time: 09:30-10:30
    Location: Gerhard M.J. Schmidt Lecture Hall
    Lecturer: Jihyun Kim
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical tool for ... Read more Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical tool for the characterization of protein structure and intermolecular interactions. However, NMR is not readily applicable to determine fast structural changes and weak interactions between molecules because of low signal sensitivity and time requirements to record multi-dimensional NMR spectra. To overcome these limits, the hyperpolarization technique of dissolution dynamic nuclear polarization (D-DNP) is combined with NMR. Not all molecules can be directly hyperpolarized. Instead, polarization transfer from hyperpolarized small molecules to a target of interest can be utilized as a means of obtaining polarization, as well as for detecting intermolecular interactions between these molecules Here, hyperpolarized water-assisted NMR spectroscopy was developed to measure intermolecular interactions with water. Firstly, the use of DNP hyperpolarization was demonstrated for the accurate determination of intermolecular cross-relaxation rates between hyperpolarized water and fluorinated target molecules.[1] Because hyperpolarized water acts as a source spin with a large deviation of the population from the equilibrium, the 19F signal on the target molecules is enhanced through NOE, allowing obtain an entire NOE buildup curve in a single, rapid measurement. When the hyperpolarized water-assisted NMR experiment is applied to a protein, water hyperpolarization can be transferred to amide protons on the protein through proton exchange. Further, this polarization spreads within the protein through intramolecular NOE to nearby protons including aliphatic groups.[2] By utilizing this polarization transfer, this method extends to measure enhanced 2D NMR spectra of the protein under folded and refolding conditions.[3] With the ability to rapidly measure protein signals that were enhanced through transferred polarization from hyperpolarized water, NMR spectra can be acquired within the timescale of the protein folding. Compared to the folded protein experiment, signals attributed to exchange-relayed NOEs are not observable in the refolding experiment (Figure 1b). These differences are explained by the absence of long-range contacts with nearby exchangeable protons such as OH protons
    Close abstract

    Life Science Lectures- Recovering lost information: potential applications in biomedical research

    Date:
    03
    Thursday
    October
    2019
    Lecture / Seminar
    Time: 10:00-11:30
    Location: Nella and Leon Benoziyo Building for Biological Sciences
    Lecturer: Prof. Yonina Eldar
    Organizer: Life Sciences
    Details: Benoziyo Biochemistry Auditorium, room 191c Light refreshment will be served at ... Read more Benoziyo Biochemistry Auditorium, room 191c Light refreshment will be served at 10:40 in the lobby
    Close details
    Abstract: The conversion of physical analog signals to the digital domain for further proc ... Read more The conversion of physical analog signals to the digital domain for further processing inevitably entails loss of information. In many modern applications, the signal bandwidths have increased tremendously, while the acquisition capabilities have not scaled sufficiently fast. Furthermore, the resulting high rate digital data requires storage, communication and processing at very high rates which is computationally expensive and requires large amounts of power. In the context of medical imaging sampling at high rates often translates to high radiation dosages, increased scanning times, bulky medical devices, and limited resolution. In this talk, we present a framework for sampling and processing a wide class of wideband analog signals at rates far below the standard Nyquist rate, by exploiting signal structure and the processing task and show several demos of real-time sub-Nyquist prototypes. We consider applications of these ideas to a variety of problems including fast and quantitative MRI, wireless ultrasound, and super-resolution in microscopy and ultrasound which combines high spatial resolution with short integration time. We then show how the ideas of exploiting the task, structure and model can be used to develop interpretable model-based deep learning methods that can adapt to existing structure and are trained from small amounts of data.
    Close abstract

    Applications of Hadamard Transform in NMR Spectroscopy

    Date:
    09
    Monday
    September
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Eriks Kupce
    Organizer: Department of Molecular Chemistry and Materials Science

    Single and multi-frequency saturation methods for molecular and microstructural contrast in human MRI”

    Date:
    20
    Thursday
    June
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Elena Vinogradov
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Magnetic Resonance Imaging (MRI) provides excellent quality images of soft tissu ... Read more Magnetic Resonance Imaging (MRI) provides excellent quality images of soft tissues and is an established modality for diagnosis, prognosis and monitoring of various diseases. Majority of MRI scans in clinical practice today report on anatomy, morphology and sometimes physiology. The new area of active studies is aimed at developing MRI contrast methods for the detection of the events at the microstructural and molecular level employing endogenous properties. Here, we will discuss methods that employ single- and multi-frequency saturation to detect events on microstructural and molecular level. First, we will describe principles and translational aspects of Chemical Exchange Saturation Transfer1(CEST). CEST employs selective saturation of the exchanging protons and subsequent detection of the water signal decrease to create images that are weighted by the presence of a metabolite or pH2. We will describe aspects of translating CEST to reliable clinical applications and discuss its potential uses in human oncology, specifically breast cancer. Second, we will describe a method called inhomogeneous Magnetization Transfer3 (ihMT), which employs dual-frequency saturation to create contrast originating from the residual dipolar couplings and thus specific to microstructure. We will focus on the application of ihMT to the detection of myelin in brain and spinal cord. Finally, we will discuss a novel exchange-sensitive method based on the balanced steady-state free precession (bSSFP) sequence as an alternative way for chemical exchange detection (bSSFPX4). Using an effective field description, similarities between bSSFP and CW application can be explored and utilized for in-vivo MRI contrast. [1] K. Ward, et.al., JMR,143,79-87 (2000). [2] J. Zhou, et.al., Nature Medicine, 9,1085-1090 (2003). [3] G. Varma, et.al., MRM, 73, 614-622 (2015). [4] S. Zhang, et.al., JMR, 275, 55-67 (2017).
    Close abstract

    Design and validation of a head coil for MRI at 7T

    Date:
    12
    Wednesday
    June
    2019
    Lecture / Seminar
    Time: 15:00-16:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Shajan Gunamony
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Radio frequency (RF) coil design for ultra-high field MRI scanners is an active ... Read more Radio frequency (RF) coil design for ultra-high field MRI scanners is an active field of research. We have recently developed an 8-channel transmit, 32-channel receive 7T head coil at the University of Glasgow. We focused on an open-faced design to make the setup less claustrophobic and more acceptable in a clinical environment. Furthermore, the coil can be used in both the scanner modes. I will also present our internal validation process which allows home-built RF coils to be used in vivo.
    Close abstract

    Non-Hydrolytic Sol-Gel Synthesis of Micro/Mesoporous Silicate and Phosphate Materials

    Date:
    05
    Wednesday
    June
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Jiri Pinkas
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Synthetic methods based on sol-gel chemistry are attractive solution-based route ... Read more Synthetic methods based on sol-gel chemistry are attractive solution-based routes to many simple and complex materials. The non-hydrolytic procedures are viable alternatives to classical aqueous techniques and these condensation reactions are inherently suitable for fabrication of mixed-metal and multimetallic oxidic and hybrid inorganic-organic systems. We developed novel non-hydrolytic sol-gel routes to several classes of porous xerogels, such as silicophosphates and -phosphonates, aluminophosphates, Al, Ti, Zr, and Sn silicates, hybrid aromatic organosilicates, and organosilicophosphates. The polycondensation reactions are based on elimination of small molecules, such as trimethylsilyl ester of acetic acid, dialkylacetamides, silylamines, ethers or alcohols. These elimination reactions provide microporous xerogels with high surface areas. Control of porosity and pore size is achieved by several methods, such as choice of suitable precursors, application of bridging groups, or addition of Pluronic templates. Residual organic groups on the surface allow for chemical modification and anchoring of various groups. Calcination in air provides xerogels that are stable at temperatures up to 500 C and show superior catalytic activity and selectivity in various catalytic reactions. The prepared xerogels were characterized by solid-state 13C, 27Al, 29Si, 31P NMR, IR, surface area analysis, DRUV-vis, TGA and XRD
    Close abstract

    Imaging the human brain: ultra-high field MRI and new biomarkers

    Date:
    26
    Sunday
    May
    2019
    Lecture / Seminar
    Time: 13:00
    Location: Edna and K.B. Weissman Building of Physical Sciences
    Lecturer: Rita Schmidt
    Organizer: Department of Physics of Complex Systems
    Abstract: Times New Roman (Headings CS) ... Read more Times New Roman (Headings CS)
    Close abstract

    Molecules in Large and Small Pores as Observed by NMR Spectroscopy. Pore Structure, Tortuosity and Molecular Interactions

    Date:
    31
    Sunday
    March
    2019
    Lecture / Seminar
    Time: 15:30-16:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Istvan Furo
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: The seminar summarizes three recent studies (1,2,3) since that share some comm ... Read more The seminar summarizes three recent studies (1,2,3) since that share some common elements: they concern porous materials and the method used is NMR spectroscopy. Yet, the aims differ. In the first study (1), the unknown is the pore structure. In particular, pore structure in hydrogels is difficult to access as water cannot be removed without affecting the pores and in the presence of water the well-honed gas sorption and mercury porosimetries just do not work. The method we invented to remedy this situation is called size-exclusion quantification (SEQ) NMR and it can be seen as the multiplexed analogue of inverse size exclusion chromatography. In effect, we sample by diffusion NMR the size distribution in a polydisperse polymer solution before and after it had been equilibrated with a porous matrix. Size-dependent polymer ingress reveals the pore structure. The method has several advantages over possible alternatives, not least its speed. In the second study (2), we sample the self-diffusion of neat water and other molecules like dimethyl sulfoxide (DMSO) and their mixtures by NMR diffusion experiments for those fluids imbibed into controlled pore glasses (CPG, pore size range 7.5 to 73 nm). Their highly interconnected structure is scaled by pore size and exhibits pore topology independent of size. Relative to the respective diffusion coefficients obtained in bulk phases, we observe a reduction in the diffusion coefficient that is independent of pore size for the larger pores and becomes stronger toward the smaller pores. Geometric tortuosity governs the behavior at larger pore sizes, while the interaction with pore walls becomes the dominant factor toward smaller pore diameters. Deviation from the trends predicted by the popular Renkin equation and variants (4) indicates that the interaction with the pore wall is not just a simple steric one. In the third study (3), the porous material is hydrated cellulose. In that matrix, we identify by using 2H MAS NMR two different groups of water molecules being in slow exchange with each other. Water molecules in one of the groups exhibit anisotropic molecular motions with a high order parameter. Based on, among other things, the observed behavior with increasing vapor pressure, we argue that this water is an integral structural element of the cellulose fibril, that itself is an aggregate of the basic units, the cellulose nanofibrils.
    Close abstract

    Spectral editing techniques for chemical exchange saturation transfer imaging

    Date:
    12
    Tuesday
    March
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Jiadi Xu
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Chemical exchange saturation transfer (CEST) imaging is a relatively new MRI tec ... Read more Chemical exchange saturation transfer (CEST) imaging is a relatively new MRI technology allowing the detection of low concentration endogenous cellular proteins and metabolites indirectly through water. CEST MRI is still under development and one major impediment for more widespread application is limited specificity due to spectral overlap of CEST signal from other metabolites and proteins. In this presentation, I will demonstrate several novel CEST spectral editing techniques developed by our group to extract information from CEST images, such as one variable delay multi pulse (VDMP) CEST that acts an exchange rate filter to separate CEST effects from the confounding factors, one ultra-short echo (UTE)-CEST method that can monitor in vivo protein aggregation process and one polynomial and Lorentzian line-shape fitting (PLOF) CEST that can detect creatine and phosphocreatine in tissue with high specialty. Their applications on the stroke and Alzheimer’s disease models will be covered. At last, I will explore one artificial neural network approach to overcome the challenges of implementing the CEST technique on 3T clinical MRI scanners.
    Close abstract

    Mn(II) EPR tracks the hydrolysis state and ATP/ADP dependent conformation in yeast Hsp90 chaperone

    Date:
    28
    Thursday
    February
    2019
    Lecture / Seminar
    Time: 14:00-15:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Angeliki Giannoulis
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Hsp90 plays a central role in cell homeostasis by assisting folding and maturati ... Read more Hsp90 plays a central role in cell homeostasis by assisting folding and maturation of many client proteins. In order to perform this chaperoning activity Hsp90 hydrolyzes ATP, which requires Mg(II) as cofactor and the hydrolysis is coupled to large global conformational changes. Hsp90 is homo-dimeric with each monomer consisting of three consecutive domains (CTD, MD, NTD). The ATPase site is found in each of the two NTDs, while the CTDs constitute the dimerization site. X-ray crystallography and FRET have provided insights on the conformational cycle of Hsp90 which involves transition from a nucleotide-free ‘open’ to a nucleotide-bound ‘closed’ conformation by dimerization of the NTDs. However, there are still open questions on whether the chaperone shifts global conformation as a consequence of hydrolysis. Here, we investigate the ATPase site and the concomitant conformational changes at various nucleotide-bound states (pre-hydrolysis, intermediate high energy and post- hydrolysis states) in yeast Hsp90 using EPR techniques. To do so, we substituted the Mg(II) cofactor with paramagnetic Mn(II) and performed hyperfine and pulsed dipolar EPR experiments, to probe short and long range interactions, respectively. Specifically, we tracked ATP hydrolysis by exploring the Mn(II) coordination by the nucleotide phosphates using 31P electron nuclear double resonance (ENDOR) spectroscopy. The interaction of the Mn(II) with protein residues in the different hydrolysis states was investigated by 14/15N ELDOR-detected nuclear magnetic resonance (EDNMR). Last, we measured the distance between the two Mn(II) cofactors in each of the monomers using double electron–electron resonance (DEER/PELDOR) spectroscopy. Here, we measured a well-defined Mn(II)-Mn(II) distance of 4.3 nm in the pre-hydrolysis state, which changes both in width and mean distance in the post-hydrolysis state providing experimental evidence to the existence of two different ‘closed’ conformations for the ATP and ADP bound states. Within our approach one can probe both local and global interactions from a single sample via exploitation of intrinsic sites (here Mg(II)->Mn(II)) that can potentially yield new structural insights previously challenging to observe with FRET and EPR using site-specific spin labeling.
    Close abstract

    Diamond quantum technologies: magnetic sensing, hyperpolarization and noise spectroscopy

    Date:
    27
    Wednesday
    February
    2019
    Lecture / Seminar
    Time: 11:00-12:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Nir Bar-Gill
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Nitrogen Vacancy (NV) centers in diamond have emerged over the past few years as ... Read more Nitrogen Vacancy (NV) centers in diamond have emerged over the past few years as well-controlled quantum systems, with promising applications ranging from quantum information science to magnetic sensing. In this talk, I will first introduce the NV center system and the experimental methods used for measuring them and controlling their quantum spin dynamics. I will mention the application of magnetic sensing using NVs through the realization of a magnetic microscope [1]. I will then describe our work on nuclear hyperpolarization, potentially relevant for enhanced MRI contrast, and research into open quantum systems and quantum thermodynamics [2]. Finally, I will present related control sequences, which can be used to perform optimized quantum noise spectroscopy, allowing for precise characterization of the environment surrounding a quantum sensor [3]. 1. E. FARCHI ET. AL., SPIN 7, 1740015 (2017). 2. HOVAV, Y., NAYDENOV, B., JELEZKO, F. AND BAR-GILL, N., PHYS. REV. LETT. 120, 6, 060405 (2018) 3. Y. ROMACH ET. AL., PHYS. REV. APPLIED 11, 014064 (2019).
    Close abstract

    NMR Across the Periodic Table: Observing "Invisible" Nuclides in Solid Materials

    Date:
    21
    Thursday
    February
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Robert Schurko
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Recent developments in pulse sequences and NMR hardware have opened up many "e ... Read more Recent developments in pulse sequences and NMR hardware have opened up many "exotic" nuclides in the periodic table to experimentation by solid-state NMR. Many of these nuclides are classified as unreceptive, and have been avoided by NMR spectroscopists and chemists in general, due to factors such as low Larmor frequencies, low natural abundances, inconveniently short or long relaxation times, etc. In addition, there are numerous systems in which these nuclides have extremely broad NMR patterns resulting from large anisotropic chemical shielding or quadrupolar interactions. Such nuclei have long been classified as "invisible", since their NMR spectra cannot be observed using standard NMR pulse sequences. In this lecture, I will show that there are several robust strategies one can apply to acquire high quality solid-state NMR spectra of a variety of nuclei, including 10B, 14N, 27Al, 35/37Cl, 47/49Ti, 59Co, 63/65Cu, 69/71Ga, 91Zr, 93Nb, 139La, 195Pt, and 209Bi. Ultra-wideline NMR spectra, when coupled with X-ray crystallography and ab initio methods, provide powerful probes of molecular structure in inorganic, organic and organometallic materials. New advances in dynamic nuclear polarization (DNP) NMR for the acquisition of ultra-wideline NMR spectra will also be discussed
    Close abstract

    2019 Gentner-Minerva Symposium

    Date:
    18
    Monday
    February
    2019
    -
    19
    Tuesday
    February
    2019
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre
    Organizer: The Dimitris N. Chorafas Institute for Scientific Exchange

    Towards plug and play parallel transmission for 7T human brain MRI with universal pulses

    Date:
    07
    Thursday
    February
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Nicolas Boulant
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Parallel transmission has been the most promising approach to counteract the rad ... Read more Parallel transmission has been the most promising approach to counteract the radiofrequency (RF) field inhomogeneity problem in MRI at ultra-high field. Despite tremendous progress made by the community for more than a decade, the technology yet has failed to be embraced in routine practice because of a more complex safety management and a cumbersome calibration procedure for each subject in the scanner. After thorough tests and validations to address the former point, universal pulses were proposed a couple of years ago to circumvent the workflow problem in head imaging at 7T. For a given RF coil, they consist of designing, offline, pulse solutions to mitigate the RF field inhomogeneity problem while being robust to intersubject variability, all within explicit hardware and safety constraints. This talk will present the latest sequence and pulse developments incorporating these solutions, now covering 3D (GRE, MPRAGE, TSE, MP-FLAIR, DIR, 3D-EPI) and 2D (GRE, MB-EPI) sequences with first routine results for fMRI (resting-state HCP-style, localizer paradigm) and ongoing clinical studies (Multiple Sclerosis), thereby making parallel transmission one step closer to clinical routine and at zero cost for the user. Perhaps interestingly, to reach the desired versatility and simplicity, some solutions were inspired from solid-state NMR methods. To date the proposed universal pulses cumulate tests on around 50 volunteers and across 4 sites. They have never failed to return brain images virtually free of B1+ artefacts at 7T.
    Close abstract

    Time-resolved neural activity and plasticity in behaving rodents using high field MRI

    Date:
    05
    Tuesday
    February
    2019
    Lecture / Seminar
    Time: 14:00
    Location: Arthur and Rochelle Belfer Building for Biomedical Research
    Lecturer: Dr. Noam Shemesh
    Organizer: Department of Brain Sciences
    Details: Light refreshments before the seminar Host: Prof. Elad Schneidman elad.schneidm ... Read more Light refreshments before the seminar Host: Prof. Elad Schneidman elad.schneidman@weizmann.ac.il tel: 2239 For assistance with accessibility issues, please contact naomi.moses@weizmann.ac.il
    Close details

    Microstructural MRI: beyond the Standard Model

    Date:
    03
    Sunday
    February
    2019
    Lecture / Seminar
    Time: 16:30-17:30
    Location: Perlman Chemical Sciences Building
    Lecturer: Dr. Noam Shemesh
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Despite the importance of tissue microstructure in health and disease, its nonin ... Read more Despite the importance of tissue microstructure in health and disease, its noninvasive characterization remains a formidable challenge. Signal representations (diffusion/kurtosis tensors) are unspecific while tissue modelling using ideal geometries representing different cellular components have failed when scrutinized vis-à-vis histology: axon diameter, for example, is overestimated by factors of >6. Biophysical models characterizing signal behavior in specific diffusion-weighting regimes (power law scaling in “q” or “t”) have been more recently proposed as more reliable means for characterizing tissues. In recent years, the most prevalent biophysical model for diffusion in tissues was termed the “Standard Model”, consisting of a sum of gaussian components (nearly always two), one of which with zero diffusivity (stick). In the lecture, we will present validity regimes for the standard model and provide evidence for its limits. We will then propose a few novel means for characterizing
    Close abstract

    A Franco-Israeli Symposium in MAGNETIC RESONANCE

    Date:
    20
    Sunday
    January
    2019
    -
    22
    Tuesday
    January
    2019
    Conference
    Time: 08:00
    Location: David Lopatie Conference Centre
    Organizer: The Helen and Martin Kimmel Institute for Magnetic Resonance Research

    Using solution NMR spectroscopy to characterise the dynamics of side chains and ions in proteins

    Date:
    17
    Thursday
    January
    2019
    Lecture / Seminar
    Time: 10:00-11:00
    Location: Perlman Chemical Sciences Building
    Lecturer: Prof. Flemming Hansen
    Organizer: Department of Molecular Chemistry and Materials Science
    Abstract: Proteins are dynamic entities and function is often related to motions on time-s ... Read more Proteins are dynamic entities and function is often related to motions on time-scales from picoseconds to seconds. Understanding not only the backbone, but also the dynamics and interactions of side chains and ions within proteins is crucial, because side chains cover protein surfaces and are imperative for substrate recognition and both side chains and ions are key for most active sites in enzymes. New NMR-based methods, anchored in 13C-direct-detection, to characterise the motions and interactions of functional side chains in large proteins will be presented. One class of experiments is aimed at arginine side chains and allows the strength of interactions formed via the guanidinium group to be quantified. NMR measurements of the solvent exchange rate of labile guanidinium protons as well as measurements of the rotational motion about the Nε-Cζ bond allows for such quantifications. Secondly, a new class of NMR experiments is presented, which relies on 13C-13C correlation spectra and allows a general quantification of motion and structure of side chains in large proteins. The new 13C-13C correlation spectra are applied to a 82 kDa protein, where well-resolved spectra with minimal overlap are obtained within a few hours. NMR-based methods to characterise potassium binding in medium-large proteins will also be presented. Due to its size, 15N-ammonium can be used as a proxy for potassium to probe potassium binding in medium-large proteins. NMR pulse sequences will be presented to select specific spin density matrix elements of the 15NH4+ spin system and to measure their relaxation rates in order to characterise the rotational correlation time of protein-bound 15NH4+ as well as report on chemical exchange events of the 15NH4+ ion.
    Close abstract