FY2019 Annual Report

Structural Celluar 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 over five years as independent company.

Part of our image processing software, i.e. for 2D-processing are being ported and implemented on reconfigurable FPGA hardware. This was initially supported with an OIST Proof-of-concept (POC) grant.

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, Staff Scientist (departed Dec 2019)
  • Dr. Helena Chan, Postdoctoral Scholar (departed Dec 2019)
  • Dr. Endang Rinawati Purba, Technician
  • Mr. Seigen Nakasone, Technician
  • Ms. Shizuka Kuda, Research Unit Administrator

Departed members:

  • Dr. Cassie-Marie Peigne, Postdoctoral Scholar (departed Aug 2018)
  • Dr. Faisal Mahmood, Student (graduated 3/30/2017)
  • Dr. Märt Toots, Student, (graduated 3/30/2017)
  • Dr. Setsuko Nakanishi, Staff Scientist (departed 12/31/2016)
  • Ms. Jiafu Zeng, Research Intern (departed March 2016)
  • Ms. Olivia Leavitt, Research Intern (departed end of Term 2, 2015)
  • Dr. Yumiko Mishima, Researcher (departed 4/30/15)
  • Dr. Pan Soonsawad, Researcher (departed 4/30/15)
  • Mr. Hirotoshi Furusho, Technician (departed 4/30/15)
  • Dr. Cayho Budiman, Researcher (shared with IPB Unit, departed 5/30/14)
  • Mr. Jakub Kolodziejczyk, Technician (departed 7/31/14)
  • Ms. Ruby May Andales, Technician (departed 7/31/14)

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: Joint research
  • Researchers:
    • Strcutural Celluar Biology Unit, OIST
    • Professor Maria Bykhovskaia, Neuroscience Unit at Wayne State University

2.2 A New Molecular Machine required for Bacterial Development into Spores

  • Type of collaboration: Joint research - 3 year grand from Australian Research Council
  • Researchers:
    • Strcutural Celluar Biology Unit, OIST
    • Prof Christopher Rodrigues, University of Technology Sydney, Australia

3. Activities and Findings

This 10th 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 intensively develop our software and also 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. Further, we have just managed to implement our full 2D image processing software for very fast noise-removal via our COMET technology. We were initially rewarded a Proof-of-Concept grant to achieve this. Currently we are busy improving our COMET technology in 2D to the FPGA chips, using the latest hardware version of the FPGA. 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.

Our second project is aimed to understand how malaria parasite uses our serum proteins to cause severe malaria in pregnant women and cause deaths and morbidity to fetus in the womb as well as women who are pregnant. In order to understand that we have resolved large complex of Var2CSA and IgM. We are now in the end-phase of data acquisition and also preparing manuscript. In this project we show, through 3D tomographic analysis, and biochemical experiments how the human IgM, our primary immune defense, forms well defined giant complexes and stabilizes host parasite interaction. We have mapped domains that play important role in this interaction. 

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. This project will proceed at slower speed, because both main researchers have got a postdoc position and an assistant professorship, respectively, in Australia. However, we continue to collaborate.

The fourth project concerns the co-interpretation of 15Å->12Å->?Å 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.

In particular we now have a technician working of the biochemistry of synaptotagmin, so that we for the first time can image the full length and membrane spanning protein. 

4. Publications

4.1 Journals

  1. Monterroso B., Zorrilla S., Sobrinos-Sanguino M., Robles-Ramos M., Alfonso C., Söderström B., Meiresonne N., Verheul J., den Blaauwen T. and Germán Rivas.
    The bacterial DNA binding protein MatP involved in linking the nucleoid terminal domain to the divisome at midcell interacts with lipid membranes. mBio. 2019. April. 10(3) e00376-19. 
  1. Riccardo Funari, Rosa Ripa, Bill Söderström, Ulf Skoglund, and Amy Q. Shen.
    Detecting Gold Biomineralization by Delftia acidovorans Biofilms on a Quartz Crystal Microbalance 2019. DOI: 10.1021/acssensors.9b01580
  1. Reetesh Raj Akhouri, Lars-Göran Öfverstedt, Gunnar Wilken and Ulf Skoglund Antibody Complexes.  In: Macromolecular Protein Complexes II: Structure and Function, p23-51. Subcellular Biochemistry 93, https://doi.org/10.1007/978-3-030-28151-9_2. (eds. J.R.Harris and J.Marles-Wright). Springer Nature Switzerland AG. (2019)
  1. Seigen Nakasone, Lars-Göran Öfverstedt, Gunnar Wilken, Ulf Skoglund.  An OpenCL Implementation of an Image Filter on FPGA. The proceedings of 2019 IEEE 5th     International Conference on Computer and Communications. IEEE, PP 272-276. Dec., 2019. Chengdu, China.  
  1. Joshua W. McCausland, Xinxing Yang, Zhixin Lyu, Bill Soederstroem, Jie Xiao, Jian Liu. Treadmilling FtsZ polymers drive the directional movement of sPG-synthesis enzymes via a Brownian ratchet mechanism doi: https://doi.org/10/101/857813  bioRxiv Reprint Nov 28, 2019
  1.  Chan H., Söderström B., Skoglund U.
     Spo0J and SMC are required for normal chromosome segregation in Staphylococcus aureus. MicrobiologyOpen 2020. DOI: 10.1002/mbo3.999
  2. Bill Söderström, Helena Chan, and Ulf Skoglund. Organizational dynamics of the Escherichia coli DNA translocase FtsK at the division septum. Under revision

4.2 Books and other one-time publications

#3 above among the articles, is a book chapter. I’ve listed it as an article because it was reviewed before acceptance.

4.3 Oral and Poster Presentations

  1. Seigen Nakasone, Lars-Göran Öfverstedt, Gunnar Wilken, Ulf Skoglund. An OpenCL Implementation of an Image Filter on FPGA. The proceedings of 2019 IEEE 5th     International Conference on Computer and Communications. IEEE, PP 272-276. Dec., 2019. Chengdu, China. 
  1. Gunnar Wilken Crosslinking Pattern Notations Workshop on Proof Theory, Model Logic, and Reflection Principles, Nov 8, 2019

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

Nothing to report

7. Other

Nothing to report.