FY2018

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. Helena Chan, Postdoctoral Scholar
  • Mr. Seigen Nakasone, Technician
  • Ms. Shizuka Kuda, Research Administrator

Departed members:

  • Dr. Cassie-Marie Peigné, Postdoctoral Scholar (Departed 8/31/2018)
  • 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)
  • Ms. Miko Yamazawa, Research Intern (departed March 2019)
  • Mr. Faisal Mahmood, Student (graduated 3/30/2017)
  • Mr. Märt Toots, Student, (graduated 3/30/2017)

2. Collaborations

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

  • Type of collaboration: Research Collaboration
  • Researchers:
    • Professor Maria Bykhovskaia, Wayne State University, Detroit, MI, USA

2.2 A New Molecular Machine required for Bacterial Development into Spores. 

  • Type of collaboration: Research Collaboration
  • Researchers:
    • Professor Christopher Rodrigues, University of Technology Sydney, Australia

3. Activities and Findings

3.1 

This 9th 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. We have now managed to implement a floating-point FFT at high speed. 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 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 end of data acquisition for our second project; a Malaria related project, getting near a publication, we hope. In this project we show, through 3D tomographic analysis, how the human IgM, our primary immune defense, forms well defined giant complexes. The latest data show that we can, for the first time, pin-point the specific binding interaction between the human IgM and a Malaria parasite protein.

The third project concerns the mysteries of bacterial division, which surprisingly is not 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. In a related project we are also looking at spores, and their membrane channels.

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

4. Publications

4.1 Journals

  1. Wilken, G.  "Pure patterns of order 2." Annals of Pure and Applied Logic 169: 54-82.
  2. Bill Söderström, Helena Chan, Patrick J. Shilling, Ulf Skoglund and Daniel O. Daley. Spatial separation of FtsZ and FtsN during cell division. Molecular Microbiology 107:3, 387-401, 2018 ,  doi:10.1111/mmi.13888
  3. Faisal Mahmood, Nauman Shahid, Ulf Skoglund and Pierre Vandergheynst. Adaptive Graph-based Total Variation for Tomographic Reconstructions. IEEE Signal Processing Letters,  doi:10.1109/LSP.2018.2816582
  4. Faisal Mahmood, Lars-Göran Överstedt, Märt Toots, Gunnar Wilken, and Ulf Skoglund. An Extended Field-Based Method for Noise Removal From Electron Tomographic Reconstructions. IEEE Access 6, 17326-17339, 2018, doi:10.1109/ACCESS.2018.2810866
  5. Faisal Mahmood, Märt Toots, Lars-Göran Överstedt, and Ulf Skoglund. Algorithm and Architecture Optimization for 2D Discrete Fourier Transforms with Simultaneous Edge Artifact Removal. International Journal of Reconfigurable Computing, Volume 2018, 17pages, 2018, doi.org/10.1155/2018/1403181
  6. Funari R., Bhalla N., Chu Kang-Yu., Söderström B. and Amy Shen. 
    Nanoplasmonics for real-time and label-free monitoring of microbial biofilm formation. 
    ACS Sensors. 2018 July. 3(8): 1499-1509.
  7. Söderström B, Badrutdinov A, Chan H, Skoglund U. (2018) Cell shape independent FtsZ dynamics in synthetically remodeled cells. Nat. Commun. 18;9(1):4323. doi: 10.1038/s41467-018-06887-7.
  8. Söderström B, Chan H, Daley DO. (2019) Super-resolution images of peptidoglycan remodelling enzymes at the division site of Escherichia coli. Curr. Genet. 65(1):99-101. doi: 10.1007/s00294-018-0869-x.
  9. Palmer S., Ren Z., Hwang G., Liu Y., Combs A., Söderström B., Vasquez P., Khosravi Y., Brady J., Koo H. and Paul Stoodely. Streptococcus mutans yidC1and yidC2 impact cell-envelope biogenesis, biofilm matrix and biophysical properties. Journal of Bacteriology. 2019 Jan. 201(1) e00396-18

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations

  1. Skoglund, U., Cold is Cool. 2018: Bob Hope Elementary School, Kadena.
  2. Soderstrom, B. Cell division in E coli: You might have heard about the Z-ring, but have you ever met his cousin, the Z-quare? 2018. Oerias, Portugal: ITQB.
  3. Soderstrom, B., Cell division in E Coli as seen with two color STED nanoscopy. 2018: Stockholm Sweden.
  4. Wilken, G. Pure Sigma 2-Elementarity Beyond the Core. 2018. Universatat Bonn: Proofs and Computation.
  5. Soderstrom, B., Introduction of Basic Research., July 2019, Goeku Junior High School, OIST

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

Nothing to report

6.1 Seminar Title in Full

Nothing to report

6.2 Something Group for Something on Something (SG2S)

Nothing to report

7. Other

Nothing to report.