MLZ Conference: Neutrons for Health

Europe/Berlin
Thomas Brückel (Forschungszentrum Jülich GmbH), Winfried Petry
Description

Scope of the Conference

The goal of health research is to improve medical care and quality of life for the population. In the future individually tailored options for prevention and treatment will play a vital role, but it will also be important to better understand the role of metabolic syndromes for the major common diseases. Understanding complex biological processes requires the use of the full scientific and analytical methods available. Particularly strong are methods that offer insight into the structure and the dynamics at the molecular scale of the processes involved. The application of neutron scattering and neutron radiation to health andlifesciences is often lesser known but neutrons target very specific problems and reveal unique information.

Neutrons penetrate deeply into biological material while distinguishing between isotopes, in particular hydrogen and deuterium. Neutron beams are unique in having wavelengths and energies that correspond, respectively, to atomic spacings or fluctuation amplitudes and excitation energies, and present negligible absorption even for relatively long wavelengths. The position of hydrogen in biological structures is obtained with atomic resolution using macromolecular neutron crystallography. Small-angle neutron scattering opens the door to structures on the nano- to micrometer scale in particular in natural environment of liquid solutions. Surfaces and interfaces are probed by neutron reflectometry, with particular attention given to biomembranes. Neutron spectroscopy provides access to the motion of atoms and molecules on microscopic timescales. Neutrons are therefore a unique non-destructive probe. 

Irradiation and medical isotope production by neutrons are another important field for the application of neutrons in health care and medical treatments. Medical diagnostics and cancer treatment using radiopharmaceuticals are one of the best ways to diagnose and treat tumours. Advance in this field is crucially dependant on the availability of innovative isotopes for initial R&D and on the capability to produce large quantities for clinical applications.

This conference covers major topics of neutron scattering and neutron radiation for health ranging from diagnosis and treatment of amyloid diseases, investigating protein folding, details of enzyme behaviour, understanding of cell-membrane interactions, identification of new drug targets and development of advanced drug-delivery systems, antibiotic resistance, treatment of genetic diseases, implants and biocompatible materials,  tissue regeneration, cancer diagnosis and therapy, radiopharmaceuticals as well as medical applications and treatments. In addition methodological instrument developments are an important contribution to enhance medical and health research with neutrons.       

The international conference “Neutrons for Health” targets scientists from all these areas of health and medicine. It will emphasize the use of neutron scattering, spectroscopy and irradiation as analytical tools for the characterization and understanding of biological systems and development and applications in medical treatments.

Topics

  • Radioisotopes for Diagnostics
  • Boron Capture Therapy
  • Neutron Irradiation Therapy
  • Structural Biology
  • Biomembranes
  • Skin Models
  • Drug Delivery Systems
  • Drug Interaction
  • Implants
  • Materials in Medicine
  • Aggregation Phenomena in Diseases
  • Signalling
  • Crowding 
Poster
Participants
  • Alberto Podjarny
  • Alexander Rudt
  • Alexandros Koutsioumpas
  • Andre Mitschler
  • Andrea Posch
  • Andreas Stadler
  • Anna Stradner
  • Artem Feoktystov
  • Birgit Strodel
  • Charlotte Lorenz
  • Christian Siewert
  • Derek Logan
  • Elliot Gilbert
  • Felix Ameseder
  • Frank Heinrich
  • Franz Wagner
  • Giorgio Schiro Schiro
  • Harald Unterweger
  • Heiko Gerstenberg
  • Heloisa Bordallo
  • Henrich Frielinghaus
  • Ignacio Porras
  • Ina Lommatzsch
  • Jeremy Lakey
  • Jeremy Smith
  • Johannes (Frank) Nijsen
  • Joke Bouwstra
  • Jose Pereira
  • Judith Peters
  • Karol Ciepluch
  • Keyun Shou
  • Laszlo Rosta
  • Laura Roxana Stingaciu
  • Luigi Paduano
  • Manuchar Gvaramia
  • Marialucia Longo
  • Marie-Claire Bellissent-Funel
  • Markus Kellermeier
  • Massimo Rogante
  • Matthew Blakeley
  • Michela Marafini
  • Nadine Sauzet
  • Nicoletta Protti
  • Olaf Holderer
  • Olaf Soltwedel
  • Oliver Buck
  • Olivier Sandre
  • Onur Karaman
  • Peter Moody
  • Peter Schurtenberger
  • Rainer Bruchhaus
  • Rainer Tietze
  • Ramona Bucher
  • Robert Emery
  • Rodriguez Loureiro Ignacio
  • Ruslan Smyslov
  • Sebastian Jaksch
  • Serena Smith
  • Stuart Koelewijn
  • Thomas Brückel
  • Thomas Gutberlet
  • Thomas Nawroth
  • Tinka Spehr-Bechmann
  • Tobias Schrader
  • Ulli Köster
  • Valeria Rondelli
  • Wiebke Lohstroh
  • Winfried Petry
  • Wolfgang Sauerwein
  • Xin Xiong
  • Éverton Carvalho dos Santos
    • 09:00 12:00
      Oral presentations I
      • 09:00
        Dynamics of concentrated protein solutions: from presbyopia to pharmaceutical formulations 30m
        Speaker: Anna Stradner (Lund University, Division of Physical Chemistry)
      • 09:30
        A combined study based on simulations, analytical ultracentrifugation and SANS to elucidate the oligomers formed by Alzheimer’s Aβ peptide 30m
        Speaker: Birgit Strodel (Forschungszentrum Jülich)
      • 10:00
        Hydrogen Bond Dynamics in Antipsychotics by Neutron Spectroscopy and Density Functional Theory 20m
        Speaker: Jose Pereira (University Of Copenhagen)
      • 10:20
        Coffee Break 30m
      • 10:50
        The stratum corneum lipid composition and organization is key factor for the skin barrier: an integrated approach of lipid models and clinical studies 30m
        Speaker: Joke Bouwstra (Division of Drug Delivery Technology, Leiden Academic Centre for Drug research, Leiden University)
      • 11:20
        Nanorheology: Using neutrons to discover the dynamics of biological membranes 20m
        Speaker: Sebastian Jaksch (JCNS at MLZ)
      • 11:40
        Complex model membranes and neutron reflectivity: a mime for cell surface interactions 20m
        Speaker: Valeria Rondelli (Università degli Studi di Milano)
    • 12:00 13:00
      Lunch 1h
    • 13:00 16:30
      Oral presentations II
      • 13:00
        Solving biomedical puzzles using tiny” perdeuterated crystals for subatomic resolution X-Ray and neutron diffraction 30m
        Speaker: Alberto Podjarny (IGBMC CNRS)
      • 13:30
        Neutrons to uncover the secrets of heme peroxidases 30m
        Speaker: Peter Moody (University of Leicester)
      • 14:00
        Analysis of protein-ligand hydrogen bonding patterns in galectin-3 using neutron crystallography to guide drug design 20m
        Speaker: Derek Logan (Lund University, Dept. of Biochemistry and Structural Biology)
      • 14:20
        Coffee Break 30m
      • 14:50
        Seeing H-atoms and protons: Enzyme mechanisms and drug design 20m
        Speaker: Matthew Blakeley (Institut Laue-Langevin)
      • 15:10
        The structure of KRas at the lipid membrane 20m
        Speaker: Frank Heinrich (Carnegie Mellon University)
      • 15:30
        How PEGylation of protein may change its structure and biological functionality 20m
        Speaker: Karol Ciepluch (Forschungszentrum Jülich)
      • 15:50
        Small Angle Neutron Scattering Instrument KWS1 for Protein Structure Determination 20m
        Speaker: Henrich Frielinghaus (JCNS at MLZ)
      • 16:10
        Drug development using information from Neutron protein crystallography 20m
        Speaker: Tobias Schrader (JCNS at MLZ)
    • 16:30 18:30
      Poster session A
      • 16:30
        Drug-Polymer and Lipid Bio-Nanoparticles for Chemo-Therapy and Cancer Prevention 5m
        Speaker: Paricahrt Thummarati
      • 16:35
        Magnetic Drug Targeting (MDT)-assisted neutron capture therapy 5m
        Speaker: Harald Unterweger (Section of Experimental Oncology and Nanomedicine (SEON), Universitätsklinikum Erlangen)
      • 16:40
        Dynamics in Denatured Proteins Investigated with Neutron Spin-Echo Spectroscopy NSE 5m
        Speaker: Felix Ameseder (Forschungszentrum Jülich)
      • 16:45
        Hydration-dependent dynamics of human telomeric oligonucleotides investigated by inelastic neutron scattering 5m
        Speaker: Marialucia Longo (JCNS at MLZ)
      • 16:50
        Investigation of self-assembling biopolymers of hGBP1 in the native farnesylated state 5m
        Speaker: Charlotte Lorenz (Forschungszentrum Jülich)
      • 16:55
        MIMAC-­‐FastN : a directional fast neutron spectrometer 5m
        Speaker: Nadine Sauzet (LPSC)
        Poster
      • 17:00
        Effect of membrane active drugs on the structure of lipid bilayers 5m
        Speaker: Manuchar Gvaramia (JCNS at MLZ)
      • 17:05
        mRNA Nanoparticles for parenteral Therapy 5m
        Messenger RNA (mRNA)-based nanomedicines constitute a new class of pharmaceutical products, with a variety of potential applications, ranging from tumor immunotherapy to protein substitution 1. In tumor immunotherapy, tumor antigen-encoding mRNA is to be delivered into APCs in order to induce T-cell mediated antitumoral responses. For systemic administration of mRNA medicines, formulations are required to deliver the RNA to the target site and promote cellular uptake and translation. Lipid- or polymer-based non-viral delivery vehicles have been demonstrated to be suitable delivery vehicles for such purpose. The formulations can be assembled by incubation of RNA to cationic counter molecules, such as liposomes, lipids, polymers or peptides using dedicated protocols under suitable boundary conditions. We have studied the molecular organization of RNA lipoplex and polyplex formulations in order to elucidate the internal molecular organization to detail and thus to derive deeper understanding of the structure function correlation within these systems. By combining small angle x-ray scattering (SAXS) and small angle neutron scattering (SANS) measurements, we obtained insight into the particle architecture of the various systems. In particular we were able to reveal how the RNA was inserted into the vehicle and correlated this with the biological activity.
        Speaker: Dr Thomas Nawroth (Gutenberg-University, Pharmaceutical Technology, Staudingerweg 5)
      • 17:10
        The Neutron Spin Echo Spectrometer @ SNS (NSE-SNS) 5m
        The NSE-SNS instrument is the first spectrometer of its class and provides ultrahigh resolution spectroscopy with a daily basis Fourier time range from 5ps up to 150ns. Using a simultaneous wavelength frame of 3-3.6 Å high data collection efficiency is achieved, allowing nearly gapless coverage of a broad wavevector-time range with only a few scattering angle settings. The NSE-SNS instrument is particularly suitable to investigate slow dynamical processes and unravel molecular motions at nanoscopic and mesoscopic scale. Investigation of macromolecular assemblies of great importance to human health is one of the important applications of NSE-SNS, attracting users with interest in biophysics and medical science all over the world. NSE technique can be successfully applied to access the domain dynamics of proteins and enzyme’s, domain dynamics that is strongly related with folding-unfolding processes within proteins [1,2] and enzymatic/catalytic reactions in enzymes so implicitly, with their biological functionality. Studies of lipid systems and biological membranes are also carried out at NSE-SNS to investigate how cell membranes organize proteins and lipids to accomplish vital physiological processes [3], and to observe the disruptive effects of various anti-inflammatory medication on membrane cell organization and the transport processes thru cell membranes [4]. [1]doi:10.1038/srep22148 [2]doi:10.1016/j.jmb.2017.03.003 [3]doi:10.1021/jacs.5b08894 [4]doi:10.1039/C6CP06202D
        Speaker: Dr Laura Roxana Stingaciu (FZJ-JCNS1@FRMII)
      • 17:15
        Studying Biological Systems over a Wide Length Scale from Angstrom to Micrometer Sizes at the SANS Diffractometer KWS-2 5m
        The small-angle neutron diffractometer KWS-2, operated by the Jülich Centre of Neutron Science (JCNS) at Heinz Maier-Leibnitz Zentrum (MLZ), is dedicated to the investigation of mesoscopic multi-scale structures and structural changes due to rapid kinetic processes in soft condensed matter and biophysical systems. Following demands from the user community, it was recently considerably upgraded,1 to boost its performance with respect to the intensity on the sample (using lenses and large sample area while maintaining the pinhole resolution), counting rate capabilities (up to 5 MHz for 10% dead time with a new 3He tubes detector supplied by GE Reuter-Stokes), instrumental resolution (Δλ/λ between 2% and 20% using a double-disc chopper with variable slit opening and TOF data acquisition), and the minimum and maximum scattering variable; Qmin = 0.0002 Å-1 (using lenses and a secondary high-resolution detector) and Qmax = 1 Å-1 (using λ = 3 Å). All these new options, and the new user-friendly control software, have significantly increased the maneuverability of the instrument. Thus, KWS-2 is a highly versatile tool that can address a broad range of structural studies over a wide length scale, between Angstrom and microns, by offering multiple working modes that can be selected and used in a direct and user-friendly manner.
        Speaker: Dr Andreas Stadler (FZ Jülich)
      • 17:20
        The cold chopper spectrometer TOFTOF and its application to Biology 5m
        TOFTOF is a cold direct geometry chopper spectrometer at the Heinz Maier-Leibnitz Zentrum (MLZ) in Garching, operated by the Technische Universität München. The instrument is dedicated to measure quasielastic scattering and low lying excitations. The large dynamical range and an energy resolution that can be freely tuned between 3 meV and 2 µeV makes TOFTOF ideally suited to probe the dynamics in biological and soft matter materials in the range of picoseconds, complementary to the time scales measured by backscattering or neutron spin echo instruments. Recent developments of the instrument such as the focusing guide to study small samples will be presented, moreover the possibilities of TOFTOF to address questions in biological and soft matter materials will be discussed. Examples include, among others, the investigation of lipid membranes relevant to Alzheimers disease [1] or the study of photoactive protein solutions [2].
        Speaker: Wiebke Lohstroh
      • 17:25
        Pilot studies on NCT feasibility to treat neurotoxic protein aggregates 5m
        AD is a form of neurodegenerative amyloidosis associated to an abnormal production of insoluble aggregates of Aβ protein which deposit in the brain as senile plaques. The aging of world population is expected to increase AD cases implying huge socio-economical costs and heightens the concern about the lack of therapeutic tools. The effectiveness of External Beam RadioTherapy (EBRT) in the treatment of TracheoBronchial Amyloidosis (TBA) was described in the 1990’s, suggesting EBRT application to AD. A physico-chemical, DNA-independent process of Aβ aggregates depolymerisation by low dose, long term fractionated radiotherapy was suggested to match the brain tolerance. Boron-NCT is a radiotherapy based on the nuclear capture reaction induced by low energy neutrons on 10B isotope, emitting two high LET secondary charged particles, an alpha particle and a 7Li recoil ion. Thanks to their short ranges in water (<10 μm), the damages are localized within the 10B loaded cell, allowing a selective treatment of diffused or infiltrating tumors. Similarly, GdNCT is based on the dose deposited selectively by the Auger electrons emitted after thermal neutron capture on 157Gd. In this case, the minimum ranges are of few tens of nm. Pure or 10B-enriched water solutions of Bovine Serum Albumin and Aβ were irradiated using standard radioactive sources or the thermal neutron field of Pavia research nuclear reactor. Some preliminary results of these studies will be presented.
        Speaker: Dr Nicoletta Protti (National Institute of Nuclear Physics INFN, Pavia Unit)
      • 17:30
        Exploring dynamic processes in biological systems with SPHERES 5m
        The neutron backscattering spectrometer SPHERES (SPectrometer for High Energy RESolution) at MLZ is a third generation backscattering spectrometer with focusing optics and phase-space transform (PST) chopper. It covers a dynamic range of ± 31μeV with a high resolution of about 0.66μeV and a good signal-to-noise ratio. The intensity has been recently doubled by the upgrade of the PST chopper. Further improvement of the instrument performance is expected from the planned upgrade of the focusing guide and the introduction of a background chopper. SPHERES enables investigations on a broad range of scientific topics. It is in particular sensitive to the incoherent scattering from hydrogen and allows to access dynamic processes up to a timescale of a few ns. Therefore it is well suited to study dynamic processes in various biological systems. Selective deuteration allows for example to follow the mobility of water on the surface of proteins (e.g. Y. Fichou et al., PNAS 112, 6365 (2015)) or measure internal protein motions (e.g. A. Stadler et al., Biophysical Journal 110, 1064 (2016)).
        Speaker: Dr Laura Roxana Stingaciu (JCNS at MLZ)
    • 19:00 21:00
      Dinner 2h
    • 09:00 12:00
      Oral presentations III
      • 09:00
        Neutrons against Cancer 30m
        Speaker: Wolfgang Sauerwein (University Duisburg-Essen, University Hospital Essen,)
      • 09:30
        Development of Intensity Modulated Fast Neutron Therapy at the University of Washington 30m
        Speaker: Robert Emery (University of Washington)
      • 10:00
        Characterisation of the secondary fast and ultrafast neutrons emitted in Particle Therapy with the MONDO experiment 20m
        Speaker: Michela Marafini (Centro Fermi, Museo Storico della Fisica e Centro Studi e RIcerche E.Fermi / INFN Sezione Roma)
      • 10:20
        Coffee Break 30m
      • 10:50
        Neutron Irradiation Therapy – the clinicians view 30m
        Speaker: Andrea Posch (Univ. Klinik für Radioonkologie-Strahlentherapie Innsbruck)
      • 11:20
        Fast neutron medical treatment – a status report 20m
        Speaker: Franz-Michael Wagner (MLZ, TUM)
    • 12:00 13:00
      Lunch 1h
    • 13:00 15:00
      Oral presentations IV
      • 13:00
        A passive mechanism of antibiotic resistance - the Impermeable Bacterial Outer Membrane 30m
        Speaker: Jeremy Lakey (Newcastle University)
      • 13:30
        Neutron Reflectometry yields distance-dependent structures of interacting membranes displaying synthetic polymers and wild-type bacterial lipopolysaccharides 20m
        Speaker: Ignacio Rodriguez-Loureiro (Max Planck Institute of Colloids and Interfaces)
      • 13:50
        Structure and Fluctuations of Lipid Nonlamellar Phases Deposited at the Solid–Liquid Interface 20m
        Speaker: Olaf Soltwedel (MLZ, TUM)
      • 14:10
        Coffee Break 50m
    • 15:00 19:00
      Conference trip
    • 19:00 22:00
      Conference dinner
    • 09:00 12:00
      Oral presentations V
      • 09:00
        A brief history of the evolution of carrier-free Lutetium-177 into a globally established isotope platform for a new class of targeted cancer therapeutics 30m
        Speaker: Oliver Buck (ITM Isotopen Technologien München AG)
      • 09:30
        Production of Mo-99/Tc-99m at FRM II - Status of the Project 20m
        Speaker: Heiko Gerstenberg (FRM II, TUM)
      • 09:50
        Neutron activation of QuiremSpheres® in FRM II 20m
        Speaker: Johannes Nijsen (Quirem Medical)
      • 10:10
        Coffee Break 30m
      • 10:40
        Nanotechnology-based Drug Delivery in Oncology - Targeted Chemotherapy and Examples for specific Radioenhancement 30m
        Speaker: Rainer Tietze (Universitätsklinikum Erlangen)
      • 11:10
        Target Nanoparticles for Cancer Therapy with Neutrons and Photons 20m
        Speaker: Thomas Nawroth (Gutenberg-University, Pharmaceutical Technology)
      • 11:30
        Neutron radiobiology experiments at ILL for improving Boron Neutron Capture Therapy 20m
        Speaker: Ignacio Porras (Universidad de Granada)
    • 12:00 13:00
      Lunch 1h
    • 13:00 17:40
      Oral presentations VI
      • 13:00
        Neutron Scattering and Drug Discovery 30m
        Speaker: Jeremy Smith (University of Tennessee/Oak Ridge National Laboratory)
      • 13:30
        SANS studies of health-related micelles and “hybrid” vesicles made of copolymers, polypeptides and phospholipids 30m
        Speaker: Oliver Sandre
      • 14:00
        Combining Neutrons and Molecular Simulations for Membrane Biophysics 20m
        Speaker: Alexandros Koutsioumpas (JCNS at MLZ)
      • 14:20
        Complementary small-angle neutron and X-ray scattering studies of Mitoxantrone loaded iron oxide nanoparticle complex for magnetic drug targeting 20m
        Speaker: Artem Feoktystov (JCNS at MLZ)
      • 14:40
        Coffee Break 30m
      • 15:10
        Multimodal Iron-Oxide Nanoparticles: from Design to in vivo Applications 20m
        Speaker: Luigi Paduano (Department of Chemical Sciences, University of Naples "Federico II")
      • 15:30
        Advanced Characterization of invasive medical devices using neutron techniques 20m
        Speaker: Massimo Rogante (Rogante Engineering Office)
      • 15:50
        Protein-solvent dynamical coupling in native proteins amyloid fibers and nano-engineered protein-polymer hybrids 30m
        Speaker: Giorgio Schiro (CNRS - Institut de Biologie Structurale)
      • 16:20
        High hydrostatic pressure specifically affects molecular dynamics and shape of low-density lipoprotein particles 20m
        Speaker: Judith Peters (Université Grenoble Alpes)
      • 16:40
        Photoactivation Reduces Side-Chain Dynamics of a LOV Photoreceptor 20m
        Speaker: Andreas Stadler (Forschungszentrum Jülich)
      • 17:00
        The neutron spin echo spectrometer J-NSE: switching on the slow motion 20m
        Speaker: Olaf Holderer (JCNS at MLZ)
    • 17:20 19:00
      Poster Session B
    • 19:00 21:00
      Dinner 2h
    • 09:00 11:00
      Oral presentations VII
      • 09:00
        Filling in the gaps: improving our quality of life by understanding hydrogen bonds 30m
        Speaker: Heloisa Bordallo (University of Copenhagen - Niels Bohr Institute & ESS ERIC)
      • 09:30
        Towards the structure of native bacterial cellulose: Is Brown's model accurate? 20m
        Speaker: Ruslan Smyslov (Institute of Macromolecular Compounds of Russian Academy of Sciences; PNPI NRC KI)
      • 09:50
        Neutrons and Health: The First Ten Years of Food Science @ ANSTO 20m
        Speaker: Elliot Gilbert (ANSTO)
      • 10:10
        Coffee Break 50m
    • 11:30 12:30
      Valedictory lunch 1h