The Simons Foundation Autism Research Initiative (SFARI) is pleased to announce that it has selected three fellows in response to the 2020 Bridge to Independence Award (BTI) request for applications (RFA).

Grants awarded through the BTI program are intended to help early-career scientists transition from mentored training positions to independent careers in autism research. Launched in 2015, the program is aimed at Ph.D.- and M.D.-holding scientists with an interest in autism research, who are currently in training positions but intend to seek tenure-track faculty positions at a U.S. or Canadian research institution during the upcoming academic year. Fellows will receive a commitment of $495,000 over three years, activated upon assumption of their faculty positions.

Fellows were selected through a competitive review process. The scientific review panel included Kamran Khodakhah, Ph.D. (professor, Albert Einstein College of Medicine); Genevieve Konopka, Ph.D. (associate professor, University of Texas Southwestern Medical Center); Brian O’Roak (associate professor, Oregon Health & Science University); Giorgia Quadrato, Ph.D. (assistant professor, University of Southern California); Gabriela Rosenblau, Ph.D. (assistant professor, George Washington University); and Mark Zylka, Ph.D. [professor and director, University of North Carolina (UNC) Neuroscience Center, UNC at Chapel Hill]. Members of the panel evaluated the quality of each applicant, the scientific merit of their research proposal and their commitment to autism research.

“BTI fellows from past years have found the program’s community support and funding  incredibly valuable assets to confidently launching their research careers in autism,” says Alice Luo Clayton, SFARI senior scientist who oversees the BTI program. “I have no doubt that this year’s fellows will also benefit from the program, especially during these uncertain times.”

“I’m thrilled to be one of this year’s BTI fellows,” says Neir Eshel, M.D., Ph.D., instructor at Stanford University. “Both the funding and the access to the SFARI scientific community will be crucial to jumpstart my research on the neural circuits underlying behaviors relevant to autism.”

The three fellows are:

• Neir Eshel, M.D., Ph.D.
  Current position:
  Instructor, department of psychiatry and behavioral sciences, Stanford University
   
  Proposed research project:
  Neural circuits of frustration and aggression
  Individuals with autism often demonstrate challenging behaviors, including aggression. The current project aims to probe the neural circuits underlying one of the most clinically relevant triggers of aggression: frustration. A behavioral paradigm in which mice learn to work for reward, which is then unexpectedly omitted, will be combined with calcium imaging and optogenetic approaches to determine whether dopaminergic neurons in the ventral tegmental area and their nucleus accumbens projections modulate responses to frustration in wild-type mice. Behavioral and neural responses to frustration in mouse models of autism will also be assessed.

 

• Ranmal Aloka Samarasinghe, M.D., Ph.D.
  Current position:
  Clinical instructor in the laboratory of Bennett Novitch, Ph.D. (University of California, Los Angeles)
   
  Proposed research project:
  A human brain organoid model of neural network dysregulation in autism
  Dysregulation of excitatory-inhibitory (E/I) balance and resultant neural network dysfunction is thought to be a common pathophysiological mechanism in autism spectrum disorder (ASD). The current proposal aims to leverage key strengths of human brain organoids, including their accessibility as an in vitro system, fidelity to in vivo human brain cytoarchitecture and cell expression, and utility in studying oscillatory network behaviors¹, to gain a deeper understanding of these mechanisms. Specifically, Ranmal Aloka Samarasinghe plans to study brain organoids that are derived from individuals with mutations in SCN8A. He has found that these organoids have a loss of gamma oscillatory power. SCN8A encodes the alpha subunit of the voltage-gated sodium channel 1.6 (Na_v6) and is strongly associated with risk for epilepsy, ASD, intellectual disability and developmental delay.

 

• Toni-Lee Sterley, Ph.D.
  Current position:
  Postdoctoral associate in the laboratory of Jaideep Bains, Ph.D. (University of Calgary)
   
  Proposed research project:
  Hypothalamic circuitry in detecting negative affective states
  An inability to accurately detect the affective states of others is a core feature in ASD and contributes to general difficulties with social communication. Toni-Lee Sterley and colleagues recently established an assay that measures the ability of mice to detect the negative affective state of a familiar conspecific during social interactions². Their initial studies of the neural circuitry underlying this ability revealed a role for corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus of the hypothalamus (PVN). The current project aims to investigate this circuit and its role in detecting a negative affective state in two genetic mouse models of ASD (Shank3B and Cntnap2 mutants).