The Simons Foundation Autism Research Initiative (SFARI) is pleased to announce that it has selected seven finalists in response to the 2017 Bridge to Independence Award request for applications (RFA).

Grants awarded through the Bridge to Independence Award program invest in the next generation of top autism investigators by helping early-career scientists transition from mentored training positions to independent research careers. The program is aimed at senior postdoctoral fellows who are currently seeking tenure-track faculty positions. This is the third consecutive year that SFARI has selected finalists as part of this program.

“It is our hope that the unique timing of these awards will help very promising investigators get their independent career off the ground and substantially contribute to autism research,” says Alice Luo Clayton, SFARI senior scientist. “We thank all those who applied and wish the finalists best of luck to secure a faculty position.”

Finalists were selected through a competitive review process. The 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); Huntington Willard, Ph.D. (director, Geisinger National Precision Health Initiative); and Mark Zylka, Ph.D. (professor, University of North Carolina at Chapel Hill). Members of the panel weighed the quality of the applicant, the scientific merit of their research proposal and their commitment to autism research.

“The BTI program is Simons Foundation’s most effective mechanism for engaging and nurturing the future scientific leaders in autism research,” says Kamran Khodakhah. “The extremely high caliber of the applicants and the novelty and high quality of their proposals made the selection process difficult and yet exciting, as I have no doubt that the awardees will make significant contributions to the field in due course.”

With their finalist notification letters in hand, applicants now have the upcoming year to secure a tenure-track faculty position at a U.S. academic institution. Once approved by SFARI, each grantee will receive a commitment of $495,000 over three years through their faculty institution.

The seven finalists are:

• Ryan Doan, Ph.D.
   
  Current position:
  Postdoctoral research fellow in the laboratory of Christopher Walsh, M.D., Ph.D. (Children’s Hospital Boston)
   
  Proposed research project:
  Identification and functional analysis of noncoding mutations in autism

  One approach that may help identify candidate recessive ASD genes is to examine ASD pedigrees where parents share ancestry. Following up preliminary findings suggesting that noncoding mutations may contribute to ASD risk via homozygous point mutations in human accelerated regions (HARs), this project aims to fully examine noncoding mutations in both consanguineous and non-consanguineous families and to assess their impact on gene expression in vitro and in vivo. With a focus on elements of the genome that may have been particularly important in human evolution, this research will not only provide a systematic analysis of noncoding mutations in autism, but also inform on the role of HARs in human unique social and cognitive capacities.

 

• Michael Hart, Ph.D.
   
  Current position:
  Research associate in the Asperger Syndrome/Autism Spectrum Program of Excellence (University of Pennsylvania)
  Former postdoctoral fellow in the laboratory of Oliver Holbert, Ph.D. (Columbia University)
   
  Proposed research project:
  Defining ASD-associated genes/variants in GABAergic structural plasticity

  Abnormalities in synaptic and structural plasticity of GABAergic interneurons, which are key to maintain inhibitory homeostasis, is thought to be important in autism spectrum disorders. The current project aims to examine the function and molecular mechanisms of known autism-associated genes on GABAergic structural plasticity in a novel, ‘humanized’ C. elegans model. This work will help define novel functions of ASD-associated genes and better understand their role in relation to GABAergic structural plasticity; moreover, it will contribute to identify modifiers of ASD genetic defects, thus helping develop potential therapeutic targets.

 

• Rebecca Muhle, M.D., Ph.D.
   
  Current position:
  Clinical instructor in the laboratory of James Noonan, Ph.D. (Yale University)
   
  Proposed research project:
  Identifying developmental pathways that regulate ASD risk networks

  As a number of high-confidence autism spectrum disorder (ASD) risk genes function to modulate the expression of larger ASD-risk networks, understanding the regulation of these ASD risk genes may help expand our knowledge of the broader developmental and biological pathways underlying ASD risk. The proposed research project will assess regulation of one such ASD risk gene, chromodomain helicase DNA-binding protein 8 (CHD8), identifying upstream modulators of CHD8 expression and assessing their ability to alter CHD8-mediated molecular phenotypes. These findings will provide a molecular connection between developmental signaling pathways and ASD risk genes, and serve as an entry point into our understanding of how diverse genetic risk factors contribute to overall ASD risk.

 

• Gabriela Rosenblau, Ph.D.
   
  Current position:
  Postdoctoral research scientist in the laboratory of Kevin Pelphrey, Ph.D. (George Washington University)
   
  Proposed research project:
  Computational neuroscience derived predictions of learning in autism

  Children with autism may present with difficulties in social learning. The proposed project will use a combination of computational, neuroimaging and behavioral analyses to provide a better understanding of social and nonsocial learning strategies in children with ASD, as well as the neural underpinnings of these processes. These analyses will then be used to identify learning markers that can predict behavioral outcomes for the Pivotal Response Treatment, a form of behavioral intervention. By identifying individual learning and neural profiles, this project will contribute a mechanistic understanding that may help clarify the phenotypic heterogeneity of autism spectrum disorders and provide new avenues for targeted behavioral interventions.

 

• Stephanie Rudolph, Ph.D.
   
  Current position:
  Postdoctoral fellow in the laboratory of Wade Regehr, Ph.D. (Harvard Medical School)
   
  Proposed research project:
  Neuromodulatory control of cerebellar non-motor function in ASD

  In the last years, both the oxytocin/arginine-vasopressin (OT/AVOP) circuit and the cerebellum have separately received increasing attention as neural systems that are potentially important in autism spectrum disorders. This project aims to better understand the role that the interaction between these two systems may play in the pathophysiology of autism. A combination of genetic, viral, in vitro and in vivo techniques will be used to assess how the OT/AVOP system modulates cerebellar activity and its impact on behavior in a mouse model of autism. This project will help explore how these two systems may interact in autism and ultimately inform on OT/AVP-based therapeutic interventions.

 

• Seth Shipman, Ph.D.
   
  Current position:
  Postdoctoral fellow in the laboratory of George Church, Ph.D. (Harvard Medical School)
   
  Proposed research project:
  Reconstructing the cellular history of neurons using molecular recordings

  The CRISPR-Cas system can be used to write changes into bacterial genomic DNA sequences in response to biological processes or external phenomena, allowing genomic data to serve as a temporally ordered and stable biological record of these events. The current proposal aims to adapt this CRISPR-Cas system for use as a cell-lineage tracking system in mammalian cells, recording and tracking the expression and temporal ordering of transcriptional events that occur during neural development and cell-fate specification. Once established, this mammalian system will be used to screen autism-associated mutations, enabling an understanding of whether and how such mutations alter neural development and cell fate.

 

• Tingting Wang, Ph.D.
   
  Current position:
  Postdoctoral scholar in the laboratory of Graeme Davis, Ph.D. (University of California, San Francisco)
   
  Proposed research project:
  The role of glial CHD2 in synaptic homeostatic plasticity and autism
  Chromodomain helicase DNA binding protein 2 (CHD2) is a component of the histone acetyltransferase protein complex Spt-Ada-Gcn Acetyltransferase (SAGA) complex and a gene associated with autism risk. The proposed project will examine the role of CHD2 and the SAGA complex in glia and identify downstream targets regulating synaptic homeostatic plasticity by using both in vitro and in vivo systems, including Drosophila and mice. This work will provide a better understanding of the role of CHD2 and glia-signaling pathways in autism spectrum disorders.