Shedding light on the causes of autism

15 April 2019

Dr Jacque Pak Kan Ip is helping to advance our understanding of autism and autism-related disorders.

Dr Jacque Ip (Croucher Scholarship 2008)Research Scientist at the Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), US focuses on applying multidisciplinary approaches to bridge the gap between molecular and systems neuroscience.

The Centers for Disease Control estimates that one in 59 children has autism. “The biological cause for autism is currently not well understood,” Ip explained. This is partly due to the complex genetic factors that influence an individual’s risk for autism, which makes it difficult to model using laboratory animals.

Ip’s lab is interested in 16p11.2 deletion syndrome, which is responsible for approximately one per cent of autism cases. This condition is caused by the deletion of a small portion of chromosome 16, resulting in the loss of more than 25 different genes.

Ip wanted to understand which of these genes was responsible for the development of autistic symptoms. He hypothesised that a gene called major vault protein (MVP) may be the culprit, since it has been previously shown to be necessary for proper brain development.

To test this idea, Ip studied mice in which one copy of the MVP gene was deleted. He applied a paradigm called monocular deprivation, in which one of the mouse’s eyelids was briefly closed for a one-week period.

Normally, the brain’s primary visual cortex (V1) responds to this lack of stimulation from the closed eye by rebalancing its functional output. This manipulation induces two stages of modification within the binocular zone of V1: first, a weakening of neuronal responses to the deprived (closed) eye, and second, a delayed feedback strengthening of responses to the non-deprived (open) eye. This process relies on neuroplasticity, the ability of neurons to modify their connections in response to environmental stimuli.

However, Ip found that the mice missing a copy of MVP did not respond normally to monocular deprivation. The transgenic mice showed impairment in the strengthening of open eye responses in V1 after seven days of monocular deprivation, resulting in reduced overall plasticity. In other words, the V1 from the MVP-deficient mice did not adapt to the reduction of visual stimulation in the way that a normal brain should.

“We were pretty excited about this, because there’s an emerging hypothesis suggesting that plasticity is a core functional deficit in autism,” Ip said. The study suggests the pathways that regulate plasticity in the brain could be key for understanding autism.

Ip plans to expand his multidisciplinary approach by applying an advanced technique called in vivo two-photon imaging. This would allow him to monitor the mice’s neuronal activity in real time.

Ip is also investigating whether any of the genes involved in neuroplasticity pathways could be druggable targets for autism. He hopes that this line of research may someday lead to a treatment.

Dr Jacque Pak Kan Ip is a research scientist at the Picower Institute for Learning and Memory in the lab of Dr Mriganka Sur at MIT. Ip earned his BSc degree from the University of Sydney. He later received his PhD in Biochemistry from the Hong Kong University of Science and Technology, where his research focused on the molecular mechanisms of neurodevelopmental disorders. He has been supported by a studentship award from the Croucher Foundation, in addition to other awards including the George K Lee Scholarship, the Sir Edward Youde Memorial Fellowship, the IBRO Rita Levi-Montalcini Research Fellowship, and HFSP Long-Term Fellowship. Ip’s goal is to apply multidisciplinary approaches and cutting-edge neurotechnology to enhance our understanding of neuropsychiatric diseases.

To view Dr Ip's Croucher profile, please click here