FY2015 Annual Report

Formation and Regulation of Neuronal Connectivity Unit

David Van Vactor, Visiting Professor

 

Abstract

Our research focuses on the conserved mechanisms that underlie the formation and maintenance of synaptic connections in order to better understand the regulatory strategies and molecular machinery required to build the metazoan nervous system.  We study post-transcriptional mechanisms upstream of signaling pathways that shape development of the Drosophila neuromuscular junction (NMJ). Through analysis of a Drosophila model for the human neurodegenerative disease Spinal Muscular Atrophy (SMA), we have collaborated with multiple laboratories to map the underlying genetic and transcriptomic network and determine how loss of the underlying gene SMN (Survival of Motor Neurons) alters NMJ development and maintenance.  By comparing the genes dependent on SMN via transcriptome level sequencing with those genes and pathways that modulate SMN in vivo phenotypes, we are identifying candidates that may explain the impact of SMN loss on NMJ function. In parallel, we study microRNA-mediated regulation of synaptogenesis, as a key mechanism acting downstream of transcription and RNA splicing that tunes the stability and translation of key synaptic effectors. As part of our research mission, we also support a Drosophila genetics core facility accessible to all other OIST units, to make this powerful invertebrate model accessible for in vivo experiments.  Finally, a key part of our unit’s mission at OIST is to create and support international educational workshops to enhance training and expand the community of young scientists who value OIST and its unique strengths.

1. Staff

  • Dr. David Van Vactor, Professor
  • Dr. Takakazu Yokokura, Group Leader
  • Ms. Seiko Yoshikawa, Technician
  • Ms. Thi Thu Van Dinh, Technician (Oct, 2015 -)
  • Ms. Kun Xiao, Technician (Oct, 2015 -)
  • Dr. Cecilia Lu, Research Scientist (STG)
  • Dr. Deena Vardhini Yeraguntla, Technician
  • Ms. Victoria Hamlin, Visiting Researcher (Jul, 2015 -)
  • Mr. Hugo de Santos, Visiting Researcher (Jul - Oct, 2015)
  • Ms. Shino Fibbs, Research Unit Administrator

2. Collaborations

  • Theme: Computational analysis of RNA splicing patterns in high-content RNAseq datasets, and conservation of RNA splicing and stability effects from Drosophila to human models of Spinal Muscular Atrophy (SMA).
    • Type of collaboration: Joint research
    • Researchers: Dr. Margarida Gama-Carvalho (University of Lisbon, Lisbon, Portugal)
       
  • Theme: Defining patterns of RNA splicing and stability characteristic of human IPS-derived mixed motor neuron model of Spinal Muscular Atrophy (SMA).
    • Type of collaboration: Joint research
    • Researchers: Dr. Lee Rubin (Dept. of Stem Cell and Regenerative Biology, Harvard University, Boston, MA, USA)
       
  • Theme: MicroRNA Modulators of Spinal Muscular Atrophy (SMA) Models in Drosophila and C. elegans.
    • Type of collaboration: Joint research
    • Researchers: Dr. Anne Hart (Dept. of Biology, Brown University, Providence, RI, USA)

3. Activities and Findings

3.1 Spinal Muscular Atrophy (SMA)

Over the past year, we have completed our transcriptome analysis of Drosophila and human iPS-derived models for SMA.  After independent expression validation in the model systems, we have used bioinformatics to define conservation and underlying gene networks of the SMA-dependent genes in fly and human.  Our analysis reveals that cytoskeletal protein networks are highly enriched in the SMN target sets, suggesting future functional experiments.

3.2 Micro RNA Regulation of Synaptic Adhesion Molecules

This year, we initialed an effort to begin profiling key neuronal subpopulations using cell sorting technology combined with cell type-specific marker expression in order to define microRNAs expressed in neural tissue and motor neurons during the initial phase of synapse formation in the late embryo.  This investment in technology development will create a platform for functional studies using the

4. Publications

4.1 Journals

Nothing to report

4.2 Books and other one-time publications

Nothing to report

4.3 Oral and Poster Presentations
  1. Van Vactor, D., A Brief History of Developmental Biology, Developmental Neurobiology Course, Okinawa, Japan, July 12, 2015
  2. Van Vactor, D., Invertebrate Embryology and Genetics, Developmental Neurobiology Course, Okinawa, Japan, July 12, 2015
  3. Yokokura, T., Elucidate mechanism of Spinal Muscular Atrophy, The Japanese Medical Network for Seriously Intractable Disease, the third annual conference, Miyagi, Japan, November 13-14, 2015
  4. Lu CS., Understanding microRNA codes in the development of neural connectivity, OIST STG Forum, Okinawa, Japan, November 25, 2015
  5. Van Vactor, D., Exploring microRNA function in the Drosophila Neuromuscular System, Kyoto University, Kyoto, Japan, December 7, 2015
  6. Van Vactor, D., Exploring microRNA function in the Drosophila Neuromuscular System, Tokyo Institute of Technology, Tokyo, Japan, December 9, 2015
  7. Van Vactor, D., How did I get here: Navigating Developmental Neurobiology, Tokyo Institute of Technology, Tokyo, Japan, December 10, 2015
  8. Lu CS., Understanding microRNA codes in the development of neural connectivity, OIST Internal Seminar, Okinawa, Japan, March 11, 2016

5. Intellectual Property Rights and Other Specific Achievements

Nothing to report

6. Meetings and Events

6.1 Developmental Neurobiology Course 2015
  • Date: July 12 - July 27, 2015
  • Venue: OIST Campus
  • Co-organizers: Drs. David Van Vactor, Gordon Arbuthnott, Ichiro Masai, and Yoko Yazaki-Sugiyama
  • Poster
  • Speakers:
    • Dr. David Van Vactor (Harvard Medical School/OIST)
    • Dr. Ichiro Masai (OIST)
    • Dr. Brian Link (Medical College of Wisconsin)
    • Dr. Jeffrey Macklis (Harvard University)
    • Dr. David Jonathan Price (University of Edinburgh)
    • Dr. Lisa Goodrich (Harvard University)
    • Dr. Tomomi Shimogori (RIKEN)
    • Dr. Gian Carlos Garriga (University of California Berkeley)
    • Dr. Zinn Kai (California Institute of Technology)
    • Dr. Mary Bernadette Kennedy (California Institute of Technology)
    • Dr. Max Erich Christian Klämbt (Universität Münster)
    • Dr. Meinertzhagen Ian (Dalhousie University)
    • Dr. Jay Parrish (University of Washington)
    • Dr. Rachel Oi Lun Wong (University of Washington)
    • Dr. Liqun Luo (Stanford University)
    • Dr. Yoko Yazaki-Sugiyama (OIST)
    • Dr. Dan Sanes (New York University)
    • Dr. Stephen Wilson (University College London)
    • Dr. Daniel Goldman (University of Michigan)
    • Dr. Pat Levitt (Children's Hospital Los Angeles)
    • Dr. Atsushi Miyawaki (RIKEN BSI)
    • Dr. Hiroshi Kohsaka (University of Tokyo) 
6.2 Collaborative International Undergraduate Workshop 2015
  • Date: August 1 - August 8, 2015
  • Venue: OIST Campus
  • Co-organizers: Drs. David Van Vactor and Jeff Wickens
  • Poster

The engine of scientific discovery harnesses a constantly evolving array of tools and strategies adapted to penetrate new frontiers in research. Innovation in our approach to challenging problems often emerges from connections made at the interface between distinct disciplines, where a contrast of perspective can offer a transformative lens to view and analyze phenomena in a new light. This special international undergraduate workshop, developed and sponsored by the Okinawa Institute for Science and Technology (OIST) Graduate University, is designed to bring students and faculty from diverse backgrounds together to collaborate and explore horizon-line questions.  Groups of students from three universities in the USA and Japan will converge in Tokyo for a special topic symposium at the RIKEN Brain Science Institute, followed by a five-day intensive workshop at the OIST campus.

Aims:

This special short course will provide an opportunity to achieve several goals:

(1) to develop an interdisciplinary introduction to quantitative methods and the transformative interface between sub-disciplines.

(2) to present paradigms in experimental design and analysis, and to organize team-based problem-solving;

(3) to create a cross-cultural experience intended to promote international collaboration at an early stage prior to graduate training;

(4) to create an opportunity of reciprocal exposure of undergraduates from different institutions and nationalities.

 

Dates: Year 1 Pilot Program: August 1-8, 2015

Joint Research Symposium: Located at RIKEN BSI Campus

 

CIUW Workshop Speakers:

OIST:

Mahesh Bandi

Bernd Kuhn

Ichi Maruyama

David Van Vactor

Jeffery Wickens

Harvard University:

Aravi Samuel

Takao Hensch

Stanford University:

Thomas Clandinin

University of Tokyo:

Akinao Nose

 

Assessments:

Team challenge experiments and problems will be presented on the first and second days of the course, and teams will spend time together working on solutions and then will present their final project solutions on the final day of the workshop.  Instructors and TAs will evaluate the process and the final presentations, and provide feedback to the student groups.  Student presentations at the poster session will also be evaluated.

7. Other

Nothing to report.