FY2017 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.

In addition, we are also developing basic mathematics to establish a more generalized information theory enabling a more quantitative use of the information in measured data.

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

Our methods are well suited for use in pharmaceutical drug research in industrial collaborations, so a big leap forward was that we managed to get a MEXT grant that funds a spin-off formation. The created spin-off has now been successfully running for four years as independent company.

1. Staff

  • Dr. Ulf Skoglund, Professor
  • Dr. Lars-Göran Öfverstedt, Staff Scientist
  • Dr. Gunnar Wilken, Staff Scientist
  • Dr. Reetesh Akhouri, Staff Scientist
  • Dr. Bill Söderström, Postdoctoral Scholar
  • Dr. Cassie-Marie Peigne, Postdoctoral Scholar
  • Dr. Helena Chan, Postdoctoral Scholar
  • Mr. Qingyuan Tian, Technician
  • Ms. Shizuka Kuda, Research Unit Administrator

Departed members:

  • Dr. Setsuko Nakanishi, Staff Scientist (departed 12/31/2016)
  • Dr. Yumiko Mishima, Researcher (departed 4/30/15)
  • Dr. Pan Soonsawad, Researcher (departed 4/30/15)
  • Dr. Cayho Budiman, Researcher (shared with IPB Unit, departed 5/30/14)
  • Mr. Hirotoshi Furusho, Technician (departed 4/30/15)
  • Mr. Jakub Kolodziejczyk, Technician (departed 7/31/14)
  • Ms. Ruby May Andales, Technician (departed 7/31/14)
  • Ms. Olivia Leavitt, Research Intern (departed end of Term 2, 2015)
  • Ms. Jiafu Zeng, Research Intern (departed March 2016)
  • Mr. Faisal Mahmood, Student (graduated 3/30/2017)
  • Mr. Märt Toos, Student, (graduated 3/30/2017)

2. Collaborations

2.1 Cell division in E.coli

  • Description: Cell division in E.coli
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Daniel Daley, Stockholm University

2.2 Structure and function of proteins in Malaria infection

  • Description: Structure and function of proteins in Malaria infection
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Mats Wahlgren, Karolinska Institutet

2.3 Combining Molecular Dynamics and Molecular Electron Tomography to create a procedure to reach a reliable atomic resolution structure of a protein

  • Description: Combining Molecular Dynamics and Molecular Electron Tomography to create a procedure to reach a reliable atomic resolution structure of a protein
  • Type of collaboration: Joint research
  • Researchers:
    • Professor Maria Bykhovskaia, Wayne State University

3. Activities and Findings

3.1 Subsection Title If Necessary

This 8th year we have continued to be very busy with further developments of our experimental protocols for our high-end light and electron microscopes and continued to develop our software, and acquiring data in our ongoing structural projects. 

In our first project, we aim at getting a significant speed increase for noise removal and focus deconvolution for acquired images. To date, we have been able to generate high speed Fast Fourier Transforms via programmed FPGA (field-programmable-gated-arrays) chips. These chips will now be augmented with full image processing software for very fast noise-removal via our COMET technology. We were rewarded a Proof-of-Concept grant to achieve this. Currently we are busy porting our COMET technology in 2D to the FPGA chips. Very high-speed computations are quite enabling in structural biology because it allows for more thorough mappings of experimental parameters as well as allowing for more experiments to be processed and using more accurate mathematical models with less truncating approximations.

We are now in the middle-end of data acquisition for our second project; a Malaria related project, with a major publication soon to come. In this project we show, through 3D tomographic analysis, how the human primary immune defense, via IgM, is being used by the invading Malaria parasite to form giant complexes, the rosetting phenomenon, in thin blood-capillaries, and they are probable candidates for causing fever. The latest data show that we can, for the first time, pin-point the binding interaction between the human IgM and the Malaria parasite protein.

The third project concerns the mysteries of bacterial division, which surprisingly is not very well understood at the molecular level. This project is evolving very robustly with several publications.

In this project we have been using super-resolution fluorescence microscopy and correlative cryo-fluorescence and cryo-electron microscopy (cryo-CLEM) in order to correlate protein localization with membrane ultra-structure during division. We have identified that the core proteins involved in this process forms multiple concentric rings, and specific well-defined supramolecular complexes and that the process of disassembly is a multistep process.

The fourth project concerns the co-interpretation of 15Å-12Å resolution tomograms of synaptotagmin and the molecular dynamics result after extensive simulations. This is in collaboration with an expert neuroscience group in the US. Our initial results are indeed very exciting, showing that these two methods give very complementary information.

Marrying the methods of tomography and molecular dynamics is totally new and potentially very powerful. We are exploiting this.

4. Publications

4.1 Journals

  1. Peigne, C.-M., A. Leger, M.-C. Gesnel, F. Konczak, D. Olive, M. Bonneville, R. Breathnach and E. Scotet (2017). "The Juxtamembrane Domain of Butyrophilin BTN3A1 Controls Phosphoantigen-Mediated Activation of Human Vgamma9Vdelta2 T Cells." J Immunol 198(11): 4228-4234.
  2. Söderström, B., H. Chan, P. J. Shilling, U. Skoglund and D. O. Daley (2017). "Spatial separation of FtsZ and FtsN during cell division." Molecular Microbiology.
  3. Wahlgren, M., S. Goel and R. R. Akhouri (2017). "Variant surface antigens of Plasmodium falciparum and their roles in severe malaria." Nat Rev Microbiol.
  4. Wilken, G. (2017). "Tracking chains revisited (revised)." Lecture Notes Series 33.
  5. Wilken, G. (2017). "Pure patterns of order 2." Annals of Pure and Applied Logic 169: 54-82.

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Akhouri, R., R, S. Goel, H. Furusho, M. Wahlgren and U. Skoglund (2017). Structure of Human IgM in complex with the Malaria protein PfEMP1, Zurich, Switzerland, Structural Biology 2017.
  2. Bailey, D. G., F. Mahmood and U. Skoglund (2017). Reducing the cost of removing border artefacts in Fourier Transforms, Bochum, DE, Interna'onal Symposium on Highly-efficient accelerators and reconfigurable technologies
  3. Daley, D. O., U. Skoglund and B. Söderström (2017). HE BACTERIAL CELL DIVISION MACHINERY IS BUILT IN MODULES., Singapore, INTERNATIONAL UNION OF MICROBIOLOGICAL SOCITIES.
  4. Friedman, S.-D., D. Baghavan, Y. Yang and G. Wilken, Eds. (2017). Sets and Computations. Lecture Notes Series, Institute for Mathematical Sciences, National University of Singapore: Volume 33. Singapore.
  5. Peigne, C.-M. (2017). Observing Malaria. OIST Campus.
  6. Skoglund, U. (2017). Molecular electron tomography to visualize individual macromolecules is running at OIST. Essam Kanda Hall, Tokyo.
  7. Skoglund, U. (2017). Molecular electron tomography can visualize individual macromolecules. OIST.
  8. Skoglund, U. (2017). 2D Fast Fourier Transform with Simultaneous Edge Artefact Removal, Tokyo, Japan, JST Conference on New Technology.
  9. Skoglund, U. (2017). Thesis Research Opportunites. OIST Campus.
  10. Skoglund, U. (2017). Defining rigid-body fitting in cryo-TEM maps. OIST Campus.
  11. Soderstrom, B. (2017). Cell division through a different perspective; super-resolution fluorescence microscopy on standing cells, Madrid, Spanish National Center for Biotchnology.
  12. Soderstrom, B. (2017). Using advanced imaging to understand bacterial cell division. Germany, New Approaches adn Concepts in Microbiology, EMBO/EMBL Symposia.
  13. Soderstrom, B. (2017). Cell division in E. coli: from initiation to completion. University of Technology Sydney (UTS), Sydney, Australia.
  14. Soderstrom, B. (2017). Internal organization of the E. coli cell division machinery and its spatial regulators, Maui, Hawaii, Winter q-bio, Maui.
  15. Tian, Q., L.-G., Öfverstedt and U. Skoglund (2017). Semi-Automatically Aligned Tilt Images in Electron Tomography, Okinawa, Japan, International Conference on Intelligent Informatics and BioMedical Sciences (ICIIBMS) 2017.
  16. Toots, M. (2017). Exploring the Potential of Cryo-Electron Tomography on Protein Nanocrystals for Molecular Structure Determination.

5. Intellectual Property Rights and Other Specific Achievements

5.1 Patent

Nothing to report

5.2 Grant

5.2.1  Support Industry Grant                                                                   1 Million Yen

5.2.2 Grant-in-Aidfor Young Scientist - Multi Year (Bill Söderström)    1 Million Yen

6. Meetings and Events

6.1 Seminar: The Pathogenesis of severe malaria and the regulation of PfEMP1-VAR2CSA translation

  • Date: Oct 13, 2017
  • Venue: OIST Campus Lab3
  • Speaker: Professor Mats Wahlgren, Karolinska Institutet

7. Other

Nothing to report.