Annual Report 2020

Solving for Early-Career Challenges in Autism Research

Autism Research Initiative (SFARI)

One of the most vulnerable stages in a scientist’s career is the transition from traineeship to professorship. In the biomedical sciences in particular, a mismatch between the number of doctoral recipients and the number of available tenure-track faculty positions has made this process increasingly difficult in recent years. “There is a logjam of highly trained scientists that can’t advance to the next level,” says Alice Luo Clayton, a senior scientist at the Simons Foundation Autism Research Initiative (SFARI). “It’s a missed opportunity for valuable talent.”

To address this issue and attract outstanding early-career scientists into autism research, in 2015 SFARI created the Bridge to Independence (BTI) program, which provides three years of funding to researchers who are finishing a mentored position, to commence as soon as they move into a tenure-track position at a U.S. or Canadian research institution. The program currently includes 31 fellows whose work spans a wide range of approaches to autism research, including genetics, molecular mechanisms and clinical science.

A 70-day-old brain organoid derived from an individual with a mutation in SCN8A, a high-confidence autism risk gene. In his Bridge to Independence project, Ranmal Aloka Samarasinghe will use this in vitro system to study the effects of SCN8A mutations on excitatory-inhibitory balance and neural oscillations in autism spectrum disorder. Credit: Ranmal Aloka Samarasinghe/University of California, Los Angeles

The award makes recipients more competitive in a tough job market, Clayton says. And once they secure a position, it lets them hit the ground running. Early-career scientists typically come under immediate pressure to apply for grants, but the BTI award “gives them breathing room to actually focus on their science for a while,” she says.

Besides funding, the program provides less tangible forms of support, from advice on negotiating job offers to an instant community of early-career autism researchers. “When you start in a new place, you don’t usually have a cohort of people who were hired at the same time,” says Rebecca Muhle, a 2017 fellow who is now an assistant professor at Columbia University. The BTI award is “a nice way to find your peers, even though they are at different institutions,” she says. “You’re part of the same BTI class.”

The program hosts an annual meeting at which the fellows explain their research (this year, due to COVID-19, the meeting was spread out over six weeks of virtual sessions). “Some of the talks are over my head, and others are completely in my wheelhouse,” Muhle says. “There’s such a breadth of experience, and it’s great to all come together with a common purpose.”

The fellows also exchange wisdom about how to meet the challenges of setting up a lab as a brand-new principal investigator. “We’re all in the same boat — we have the same challenges, the same fears, the same excitement, the same roadblocks,” says Stephanie Rudolph, a 2017 fellow who is now an assistant professor at Albert Einstein College of Medicine in New York.

Spontaneous activity of in vitro cultured neurons recorded through a multielectrode array. Credit: Yun Li laboratory/University of Toronto

Several senior autism researchers also attend the meeting, to advise the fellows on matters such as how to recruit students and postdocs, craft a grant proposal, strategize for collaborations and preserve time for research amid the competing demands of a tenure-track professorship.

“There are all these skills that a young scientist doesn’t really have, because no one taught them,” Rudolph says. “We were taught as postdocs to be good scientists. But now we’re also entrepreneurs and mentors and teachers.”

Although some fellows planned all along to do autism research, others were drawn into the field by the BTI program, bringing a diverse array of backgrounds and expertise into autism research. Rudolph, for instance, studied basic synaptic physiology, but she is now examining how disruption in the cerebellum may contribute to autism-associated behaviors. “Writing the BTI grant and thinking about the relevance of my research for autism has profoundly changed how I think about my science,” she says. “It has opened up a whole world of thinking about clinically relevant questions.”

Multicolor dopaminergic neurons in the mouse ventral tegmental area and substantia nigra pars compacta following systemic delivery of AAV-PHP.eB-Th-VAST vectors. Bridge to Independence fellow J. Elliott Robinson used this technique to study alterations in neuronal morphology in a mouse model of neurofibromatosis type 1, a neurodevelopmental condition that is also the focus of his Bridge to Independence project. Credit: Gerard Coughlin and J. Elliott Robinson/Viviana Gradinaru laboratory at the California Institute of Technology

For Muhle, a physician, it was not clear until she received the BTI grant that she would be able to obtain a tenure-track position and an independent laboratory. “BTI was what allowed me to stay in research and have my own lab,” she says. “It was the tipping point in my trajectory.”

Muhle is now studying how changes in the expression of the autism risk gene CHD8 affect biological pathways and symptoms such as seizures in mice that have only one functioning copy of the gene. She also sees patients with neurodevelopmental disorders in her clinic. “I hope in the future we’ll come to a place where we’re able to improve things for our patients, in a way that will enable them to live their best lives,” she says.