SFARI announces 2018 Bridge to Independence awardees

Reconstruction of a dendritic segment in mouse hippocampus. Rotating view of a serial block face scanning electron microscopy reconstruction of a CA3 apical dendritic segment (in grey) and associated mossy fiber inputs (in color) from a wild-type mouse. Peng Zhang and colleagues found marked differences in the structure of these synapses in mice lacking heparin sulfate on neurexin-11. He plans to extend these studies as a Bridge to Independence awardee. Video from Zhang P. et al.1

The Simons Foundation Autism Research Initiative (SFARI) is pleased to announce that it has selected four awardees in response to the 2018 Bridge to Independence Award request for applications.

Launched in 2015, the Bridge to Independence Award program helps early-career scientists transition from mentored training positions to independent careers in autism research. The program is especially aimed at senior postdoctoral fellows who are currently seeking tenure-track faculty positions. After being notified, the awardees will have the upcoming year to secure a tenure-track faculty position at a U.S. academic institution. Once approved by SFARI, each awardee will receive a commitment of $495,000 over three years through their faculty institution.

“We hope these career awards will help young investigators interested in autism research become the next generation leaders in the field,” says Alice Luo Clayton, SFARI senior scientist.

Finalists were selected through a competitive review process. The distinguished scientific review panel included Kamran Khodakhah, Ph.D. (professor, Albert Einstein College of Medicine), Story Landis, Ph.D. (former director of the National Institute of Neurological Disorders and Stroke, 2003-2014) and Mark Zylka, Ph.D. (professor and director, Neuroscience Center, The University of North Carolina at Chapel Hill). Members of the panel weighed the quality of the applicants, the scientific merit of their research proposal and their commitment to autism research.

“This is a unique program for postdocs who want to move on to the next stage in their career,” says Zylka. “The quality of the applications that we reviewed this year was very high, and I look forward to hearing about the contributions to the field that these awardees will make in their independent labs.”

The four awardees are:

  • Reza Kalhor, Ph.D.

    Current position:
    Research fellow in the laboratory of George Church, Ph.D. (Harvard Medical School)

    Proposed research project:
    Developmental barcoding and whole-brain lineage mapping in autism mouse models
    Establishing single-neuron level, whole-brain maps would permit a comprehensive understanding of the brain’s lineage tree and how it relates to connectivity and cognitive functioning in health and in neurodevelopmental disorders such as autism spectrum disorder (ASD). To address the challenges associated with high-resolution developmental mapping of neurons, the proposed project will build upon prior mouse barcoding and in situ sequencing technologies to create a mouse model for in vivo barcoding of the brain and integrate this model with cutting-edge single-cell sequencing technologies in order to obtain lineage maps at a single-neuron resolution in both neurotypical and Cntnap2 and MeCP2 mutant mice. The creation of these detailed developmental maps will help understand ASD biology and its impact on brain function and will further our ability to classify distinct ASD subtypes.
  • Xin Tang, Ph.D.

    Current position:
    Postdoctoral associate in the laboratory of Rudolf Jaenisch, M.D. (Whitehead Institute for Biomedical Research)

    Proposed research project:
    Restoration of KCC2 expression as a potential therapeutic avenue to treat autism spectrum disorder
    Mutations in KCC2 (SLC12A5) regulatory regions have been linked to autism spectrum disorder (ASD). This project proposes to validate the hypothesis that reduction in KCC2 expression is a core feature of a variety of mouse and stem-cell-derived neuron models of ASD and to elucidate the molecular pathways underlying this dysregulation. A CRISPR-based activation/inhibition screening platform to identify compounds that pharmacologically upregulate KCC2 expression will also be developed, and the utility of such compounds to therapeutically rescue ASD phenotypes in the cell and mouse model systems will be assessed. The results of this project will provide valuable insights into the mechanisms underlying KCC2 dysregulation in ASD and potential therapeutic avenues for treatment of KCC2-mediated ASDs.
  • Donna Werling, Ph.D.

    Current position:
    Postdoctoral scholar in the laboratories of Matthew State, M.D., Ph.D. and Stephan Sanders, B.M.B.S., Ph.D. (University of California, San Francisco)

    Proposed research project:
    Identification and characterization of sex-differential risk mechanisms for autism
    Autism spectrum disorder (ASD) is consistently diagnosed at least three times more frequently in males than in females, but the molecular, cellular and developmental mechanisms underlying sex-differential ASD risk remain unclear. Building upon prior work, this research proposes to characterize sex differences at the tissue and cellular level in both postmortem human brains and mouse models of ASD, and to probe the relationship between sex-differential expression and ASD-associated pathways in mouse models of ASD risk genes. By using transcriptomic screening approaches to identify and validate biological pathways at the intersection of sex-differential and ASD-associated neurobiology, this proposal will aid in our understanding of the neurobiology underlying male bias in ASD prevalence.
  • Peng Zhang, Ph.D.

    Current position:
    Research associate in the laboratory of Ann Marie Craig, Ph.D. (University of British Columbia)

    Proposed research project:
    The role of HS 3-O-sulfation in synapse development
    Neurexin-neuroligin binding is essential for appropriate synaptic development and function, and mutations in neurexins and neuroligins have been linked to autism spectrum disorder (ASD). Peng Zhang and colleagues recently found that attachment of a glycan heparan sulfate (HS) and further 3-O-sulfation of the HS moiety regulate synaptic structure and function by altering neurexin-ligand binding affinities. The current project now proposes to assess how enhancements to and blockade of HS 3-O-sulfation alter neurexin-ligand binding, how this affects synaptic function in ASD mouse models and whether such modulations could correct synaptic deficits seen in neurexin-linked ASD mouse models.

Reference

  1. Zhang P. et alCell 174, 1450-1464 (2018)  PubMed
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