FY2011 Annual Report

Structural Cellular Biology Unit

Professor Ulf Skoglund

Abstract

Our unit runs research projects that concern method developments, applications, and rewarding and exciting collaborations with other groups in order to understand more of the function of proteins in cells and tissues.

We mainly use the techniques of electron microscopy, including molecular electron tomography, as the main tools in our unit, though we will draw upon well-established complementary techniques when called for.

This second year we have been very busy completing the procurement of two electron microscope instruments and major auxiliary specimen preparation instruments, continuing developing our software, hiring coworkers and initializing realistic research project to run once we have the instruments (i.e. a project concerning the Ryanodine receptor and its complexes). Just prior two the end of FY 2011 we managed to get our first test-images from the cryo-TEM.

Our method is well suited for use in pharmaceutical drug research in industrial collaborations, so a big leap forward was that we managed to transfer the patent rights for our procedures to OIST. We have also started a proof-of-concept structural determination project on a smaller sized protein (about 32 kD) in collaboration with a well-known Japanese pharmaceutical company.

1. Staff

  • Lars-Göran Öfverstedt, Researcher
  • Yumiko Mishima, Researcher
  • Gunnar Wilken, Researcher
  • Cahyo Budiman, Researcher (Shared with IPB Unit)
  • Hirotoshi Furusho, Technician
  • Jakub Kolodziejczyk, Technician
  • Shizuka Kuda, Research Administrator

2. Collaborations

  • Theme:KcsA Potassium channel
    • Type of collaboration: Research Collaboration
    • Researchers:
      • Professor Shigetoshi Oiki, University of Fukui
  • Theme:Regularization software to enable data processing from their phaseshift TEM imaging
    • Type of collaboration: Research Collaboration
    • Researchers:
      • Dr. Kazuyoshi Murata, National Institute for Physiological Sciences
  • Theme: Ryanodine receptor and its complexes also in tissue
    • Type of collaboration: Research Collaboration
    • Researchers:
      • Professor Ichiro Maruyama, OIST
  • Theme: General transcription regulator Glucocorticoid receptor
    • Type of collaboration: Research Collaboration
    • Researchers:
      • Professor Örjan Wrange, Karolinska Institutet
  • Theme: Small Protein structural characterization
    • Type of collaboration: Research Collaboration
    • Researchers:
      • Shionogi Pharmaceutical
  • Theme: 3D reconstructions of nanoparticles
    • Type of collaboration: Research Collaboration
    • Researchers:
      • Professor Mukhles Sowwan, OIST

3. Activities and Findings

3.1

Our first activity has been concerned with completing the initial setup of the cryo-EM laboratory: installment of the two microscopes Titan Krios and the Helios 650. Titan Krios is a 300 keV TEM microscope with a XFEG beam gun and a Falcon direct electron detector, thus no fluorescent screen is needed during exposures. The Helios 650 is a FIB SEM with Gallium ions/atoms as specimen ablation source. It has a cryo-specimen handling system. We have also installed the other big instruments like a cryo-microtome and a high-pressure freezer. Basically we could start the first tentative tomographic tilt series data acquisitions just around the end of FY 2011 from our Titan Krios.  The specimen handling practicalities were still not finalized at end of FY 2011 for the Helios 650, due to needed cryo-chamber modifications to maintain high vacuum over a longer time to enable specimen data collections.

Secondly we have finalized the major upgrade of our software to what we call 5.4 of our EM-suite of programs including the regularization of tomography reconstructions.  This version is also enabled for the new type of data that we acquire from the Titan Krios Falcon detector. The new version is quite stable (our opinion) and will be the first version that we help other Japanese groups to run. The code has been speeded up considerably by parallelization and can now also be run both on our iMac’s and the HPC Linux cluster machines.

Thirdly we have initiated several new collaborative projects aimed at macromolecular  characterization.

See above for Collaborations

The collaborations with professors Neus Visa and Ivar Hordvik are pending funding decisions.

These are all newly started and we have not yet reproduced and confirmed findings.

4. Publications

4.1 Journals

  1. Rullgard, H., Ofverstedt, LG., Masich, S., Daneholt, B., Oktem, O. Simulation of transmission electron microscope images of biological specimens. Journal of Microscopy 243, 234-256, doi: 10.1111/J.1365-2818.2011.03497.x (Sep 2011)
  2. Weiermann, A., Wilken, G. Ordinal arithmetic with simultaneously defined theta-functions. Mathematical Logic Quarterly 57, 116-132, doi: 10.1002/malq.200910125 (Apr 2011)
  3. Carlson, TJ., Wilken, G. Tracking chains of Sigma(2)-elementarity Annals of Pure and Applied Logic  163, 23-67, doi: 10.1016/j.apal.2011.08.003 (Jan 2012)
  4. Carlson, TJ, Wilken, G. Normal forms for elementary patterns. The Journal of Symbolic Logic 77: 174-194 (Mar 2012)
  5. Wilken, G., Weiermann, A. Derivation lengths classification of Godel’s T extending Howard’s assignment.  Logical Methods in Computer Science 8, 1-44 (Mar 2012)

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Skoglund, U. Using Molecular Electron Tomography to see macromolecules in 3D, Participants of the 28th International Symposium on Space Technology and Sciences, OIST Campus, Jun 9, 2011
  2. Skoglund, U. Molecular Electron Tomography seeing macromolecules in 3D, University of Ryukyus Faculty Members Visit, OIST Campus, Jun 23, 2011
  3. Skoglund, U. Use of Molecular Electron Tomography to visualize macromolecules in 3D, Invited Seminar at University of Fukui, Dec 11, 2011
  4. Skoglund, U. Use of Molecular Electron Tomography to visualize macromolecules in 3D, Review and Assessment for IGA Collaboration by External Experts at NAIST, Japan, Feb 24, 2011
  5. Öfverstedt, L. Molecular Electron Tomography, International Joint Seminar for Bio-imaging Sciences-Structural Biology Division of Japan Microscopy Society, Singapore, Jan 2012
  6. Wilken, G. Derivation lengths classification of Godel’s T as a prototype of higher order rewrite systems, Invited talk at Logic Colloquium 2011, Spain, Jul 13, 2011
  7. Wilken, G. Infinitary Concepts and Gode’s T, Infinity Conference, Spain, Jul 19, 2011
  8. Wilken, G, On Elementary Patterns of Resemblance, invited talk at Oberwolfach Seminar, Germany, Nov 10, 2011
  9. Wilken, G, Die Unvollstandigkeit der Peano Arithmetik, Germany, Nov 14, 2011
  10. Wilken, G, Goodstein-Folgen und Unabhangigkeit, Habilitationskolloquium, University of Munster, Nov 16, 2011
  11. Furusho, H, Lipid Nanotube Encapsulating Method for Nano size Particles, International Joint Seminar for Bio-imaging Sciences-Structural Biology Division of Japan Microscopy Society, Singapore, Jan 2012

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 Seminar

  • Date: May 20, 2011
  • Venue: OIST Campus
  • Speaker: Dr. Andreas Brech (Institute for Cancer Research)

6.2 Workshop: CCP4-OIST School

  • Date: December 5, 2011 - December 9, 2011
  • Venue: OIST Seaside House
  • Speakers:
    • Professor Fadel A Samatey (OIST)
    • Professor Ulf Skoglund (OIST)
    • Dr Charles Ballard

6.3 Seminar

  • Date: February 14, 2012
  • Venue: OIST Campus
  • Speakers: Dr. Kazuyoshi Murata (NAPS)

7. Other

Nothing to report.