FY2016 Annual Report

Principal Investigator: Ichiro Maruyama
Research Theme: Information Processing by Life

Abstract

In order to survive, animals must closely monitor environmental changes, and must keep the memory as experiences to adjust their behavior to the environment. We are interested in understanding how neuronal networks process environmental information to regulate animal behaviors, including decision-making, learning and memory. In previous years, we developed protocols to study associative learning and memory in the nematode Caenorhabditis elegans as a model organism. C. elegans is innately attracted to propanol, a short-chain alcohol, and avoids acid such as pH 4.0. After repeated conditioning C. elegans with propanol and acid, it associates the two stimuli and avoid propanol. C. elegans retains the memory up to 24 hours as long-term associative memory. In the present fiscal year, we have been trying to identify neuronal circuits responsible for the memory trace in the C. elegans nervous system by using multiple techniques including genetic rescue experiments and Ca2+ imaging analysis of neuronal activity. Optogenetics is also used to induce memories by expressing an artificial ion channel such as channelrhodopsin in specific neurons. Electrophysiology has been used to understand how electrical signals are transmitted along neurites of major gustatory sensory neurons. To understand decision-making in C. elegans, we also started analysis of its behavior on salt gradients.

We are also interested in understanding how neurons/cells detect extracellular information and transmit it into inside the cell. For the last three decades, ligand-induced dimerization has been widely thought to be a common property of transmembrane signaling by receptors for all known growth factor and cytokines, among others. In previous years, however, we found that receptors for epidermal growth factor (EGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have a preformed, yet inactive, dimeric structure prior to ligand binding. Based on the results, we proposed an alternative ‘rotation model,' in which ligand binding to the extracellular domains induces a rotation of the transmembrane domains parallel to the plane of the membrane. This activates the intracellular domains, which often encode or physically interact with a kinase, by rearranging their dimeric structures. To examine the model, we are currently trying to determine three dimensional structures of the receptor dimers. We are also analyzing co-operative interaction between EGF and its receptor EGFR, which is observed only in dimers.

These results provide insights into the molecular mechanism underlying information transfer from the outside of neurons/cells to the inside, as well as an understanding of neuronal networks responsible for associative learning and memory. These findings may also be invaluable in developing pharmaceuticals for human diseases such as cancers and mental diseases.

1. Staff

  • Dingze Mang, Postdoctoral Scholar (from June 6, 2016)
  • Yuto Momohara, Postdoctoral Scholar (from November 1, 2016)
  • Andrew Mugo, Postdoctoral Scholar
  • Takashi Murayama, Technical Staff
  • Hitomi Ohtaki, Research Unit Administrator
  • Endang Rinawati Purba, Postdoctoral Scholar
  • Eiichiro Saita, Technical Staff
  • Vimbai Samukange, Postdoctoral Scholar

2. Graduate and other students

  • Saahil Acharya, Rotation Student (May 1, - August 31, 2016)
  • Aliya Mari Adefuin, Rotation Student (September 1, - December 29, 2016)
  • Tosif Ahamed, PhD Student
  • Dong Cao, Rotation Student (January 11, - April 30, 2017)
  • Tomohiro Fujita, Research Intern (January 12, - March 31, 2017)
  • Hannah  Hendry, Rotation Student  (July 7, - September 26, 2016)
  • Tsung-Yen Huang, Rotation Student (January 11, - April 30, 2017)
  • Kazuto Kawamura, PhD Student     
  • Viktoras Lisicovas, PhD Student     
  • Mathias  Mikkelsen, Rotation Student (May 1, - August 31, 2016)

3. Collaborations

3.1 Functional analyses of small G protein and their downstream proteins

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

3.2 Study of signal transduction pathways that regulate cellular functions

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

3.3 Social interaction and anxiety of genetically modified mice

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

3.4 Analysis of Rap2 function in skin wound healing

  • Type of collaboration: Joint research
  • Researchers:
    • Ken-ichi Kariya, University of the Ryukyus
    • Tsuyoshi Asato, University of the Ryukyus
    • Kimiko Nonaka, University of the Ryukyus

4. Publications

4.1 Journals

  1. Canu, N., Pagano, I., La Rosa, L. R., Pellegrino, M., Ciotti, M. T., Mercanti, D., Moretti, F., Sposato, V., Triaca, V., Petrella, C., Maruyama, I., Levi, A. and Calissano, P. (2017) Association of TrkA and APP is promoted by NGF and reduced by cell death-promoting agents. Front. Mol. Neurosci.  (doi: 10.3389/fnmol.2017.00015).  
  2. Maruyama, I. N. (2017) Receptor guanylyl cyclases in sensory processing. Front. Endocrinol 7, 173 (doi: 10.3389/fendo.2016.00173). 

4.2 Oral and Poster Presentations

  1. Saita, E., and Maruyama, I. (2016). Multi-color TIRF imaging of epidermal growth factor receptor in living cells. ANDOR ACADEMY OKINAWA AT OIST Lab1 LevelB053 (May 19, 2016)
  2. Lisicovas, V., Harding, R., Maruyama, I., and Dani, K. (2016). Imaging the Formation of Memories in C. Elegans using a Wide-Field Temporally Focused Two-Photon Microscope. Ultrafast Dynamics at the Nanoscale. OIST B250 (July 8, 2016)
  3. Murayama, T., and Maruyama, I. (2016). Neural circuit basis for decision-making in C. elegans chemotaxis. In The 39th Annual Meeting of the Japan Neuroscience Society. Yokohama, Japan (July 20-22, 2016)
  4. Ahamed, T. (2016). Behavioral Embedding Suggests Multiple Chaotic Dimensions Underlie C. elegans Locomotion. CeNeuro 2016.Nagoya, Japan (July 27-30, 2016)
  5. Kawamura, K. (2016). Forward genetic screen for adult-onset motor deficits. CeNeuro 2016. Nagoya, Japan (July 27-30, 2016)
  6. Lisicovas, V., and Maruyama, I. (2016). Aversive conditioning of C. elegans using optogenetic stimulation to mimic chemosensory responses. CeNeuro 2016.Nagoya, Japan (July 27-30, 2016)
  7. Murayama, T., and Maruyama, I. (2016). Neural circuit basis for the behavioral switch in C. elegans chemotaxis to alkaline pH. CeNeuro 2016.Nagoya, Japan (July 27-30, 2016)
  8. Maruyama, I. (2016). Toward mechanism-based anti-cancer drug development. In Drug Discovery & Therapy World Congress 2016 (The John B. Hynes Veterans Memorial Convention Center, Boston, USA (Aug 22-25, 2016)
  9. Maruyama, I. (2016). Environmental alkalinity sensing mediated by the transmembrane guanylyl cyclase GCY-14 in C. elegans. In 4th Global Experts Meeting on Neuropharmacology. San Antonio, Texas, USA (September 15-17, 2016)
  10. Murayama, T., and Maruyama, I. (2016). Neural circuit basis for decision-making in C. elegans chemotaxis. Neuroscience 2016. San Diego, CA, USA (November 12-16, 2016)
  11. Maruyama, I. (2016). Application of photonics to biology: from single molecule observation to memory formation. 1st Meeting of Photonics Research Section, Japanese Society for Applied Physics. Okinawa, Japan (December 1-2, 2016)
  12. Maruyama, I. (2016). Activation of type-1 transmembrane receptors via a common mechanism? The “rotation model”. 5th International Conference on Biotechnology and Bioengineering. Bangkok, Thai (December 8-10, 2016)

5. Meetings and Events

5.1 Seminar

Title: Expression of the fructose receptor BmGr9 and its involvement in the promotion of feeding, suggested by its co-expression with neuropeptide F1
  • Speaker: Dingze Mang
  • Date: April 5th 2016
  • Venue: OIST Lab1 C015
Title: Neuroethological analysis of dominance hierarchy formation through agonistic interaction in crayfish
  • Speaker: Yuto Momohara
  • Date: August 8th 2016
  • Venue: OIST Lab1 C015
Title: Molecular basis for a future HIV Cure
  • Speaker: Jonathan Karn
  • Date: November 28th 2016
  • Venue: OIST Lab1 C015