BMB Blog

1 in 36 children in the United States have Autism Spectrum Disorder (ASD), which consists of core symptoms including “social communication challenges and restricted, repetitive behaviors.”^{(1, 2)} This would mean that there is one student with ASD in every other classroom in America, and this estimate doesn’t even take into account the millions of adults with ASD.⁽³⁾ Despite the broad impact of ASD, we still don’t know enough about what causes it. This is largely due to the “S” in ASD – “Spectrum.” ASD can present across wide levels of severity and symptom combinations, and is thought to be caused by a complicated interplay between genetics and environment.⁽⁴⁾ The diversity in the causes of ASD and its effect on people’s lives makes it difficult to apply discoveries in the lab about one specific cause of or risk factor for ASD to large numbers of patients. So, while many many scientists are working hard to uncover the molecular mechanisms driving ASD, progress can feel slow when viewed from the outside.

Luckily, deciphering the complex risk factors behind ASD is the passion of our own Dr. Summer Thyme. “Neurodevelopmental disorders [like ASD] are very important, and there are really no treatments,” says Dr. Thyme. In fact, “pharmaceutical companies don’t work on [finding cures for neurodevelopmental disorders] at all, compared to diseases like cancer and ALS.” This gap in knowledge is one she and her team of researchers are determined to fill. 

Dr. Thyme uses what some consider to be an unusual tool to study brain development – her lab uses small fish to study humans. Zebrafish are an incredibly powerful model for studying the development of vertebrate organisms, and are used by labs all over the world to study many different human diseases.⁽⁵⁾ Even though zebrafish appear to be very different from humans, their cellular processes are remarkably similar to ours.⁽⁶⁾ Importantly, over 80% of genes known to be involved in human disease can also be found in zebrafish.⁽⁷⁾ However, unlike humans, a single zebrafish can produce hundreds of embryos every week, and they can grow from a freshly fertilized egg to a juvenile fish ready for relevant behavioral testing in just three weeks.⁽⁸⁾ In fact, fish larvae can even be tested for social behavior tendencies starting at just four days after fertilization!⁽⁹⁾ This allows scientists like Dr. Thyme to evaluate large numbers of risk factors quickly and powerfully.

That is exactly what the Thyme lab did in their most recent study (currently awaiting peer review).⁽⁹⁾ Dr. Thyme and her lab generated zebrafish mutants for 17 different genes known to increase the risk of developing ASD. They observed hundreds and hundreds of fish as they grew from embryos to adults, all the while measuring their brain size, brain activity, stimulus sensitivity, social behaviors, and more. These data confirmed what scientists have learned in other studies about the molecular mechanisms driving ASD, but they also suggested new pathways that might contribute to ASD risk.

One example is the gene arid1b (AT-Rich Interaction Domain 1B). This gene was found to be mutated in several ASD patients across multiple independent studies, identifying it as a strong risk factor for ASD in humans. Indeed, in Dr. Thyme’s study, the loss of arid1b led to changes in larval behavior and decreases in the willingness of juvenile fish to socialize with other fish, which mimics some of the core symptoms of ASD. Unfortunately, the protein encoded by the gene arid1b is not a good candidate for pharmaceutical targeting due to its structure and function inside the cell - it collaborates with many other proteins to manage what DNA is accessible for transcription in the cell.  Drugs have a hard time reaching proteins buried deep in the nucleus of the cell. Drugging a nuclear protein like Arid1B would be like trying to get your friend’s attention across a busy five-lane highway by yelling and waving your arms – most of the time, it just won’t work.

Interestingly, when Dr. Thyme and her team looked more closely at the brains of the arid1b mutant fish, they found that their cells were making lots more of the protein encoded by the gene rln3a (Relaxin 3A) than their non-mutated siblings. This gene codes for a protein that acts as a receptor in the brain and other parts of the body. This was exciting news for Dr. Thyme and her team, as receptors are much easier to target with pharmaceuticals, since their major role in our cells is to bind to chemicals that can be mimicked by drugs. Instead of yelling to your friend across the highway, drugging a receptor like Rln3A is more like traying to get your friend’s attention as you walk past each other on a sidewalk. This discovery opens up a new potential therapeutic pathway for treating a subset of ASD patients.

Some advocates for people diagnosed with ASD disapprove of the rhetoric insisting that ASD needs to be cured. Many hold fast to the idea that the issue with ASD is not the individual, but the unyielding society in which they are forced to live. While there is certainly much to be said about accessibility and diversity in society, the goal of research like Dr. Thyme’s is to help ASD patients navigate the world we all live in with greater ease.

On this Autism Awareness Day, we honor the multi-faceted challenges facing the ASD community. As scientists, we hope to use the power of discovery to make people’s lives better. We are looking forward to the discoveries sure to come from the Thyme lab’s innovative research techniques. If you’re interested to learn more about research in the Thyme lab, check out their website at this link. To find out more about our department’s dedication to research that can impact our everyday lives, check out our website at this link.