Institute for Basic Science
AsianScientist (Jun. 28, 2019) – The brain is made up of billions of neuronal cells, between which exist gaps called synapses that amount to over a hundred trillion. Across synapses, chemical messengers called neurotransmitters pass from one neuron to the next through protein channels, allowing the flow of electrical signals through the nervous system to enable neural functions ranging from memory to feelings.
But when psychiatric disease strikes, how exactly are these synapses involved in disease manifestation? This remained a mystery until 1995, when Professor Kim Eunjoon, director of the Institute of Basic Science’s Center for Synaptic Brain Dysfunctions, South Korea, shed light on the components required to assemble a functional synapse. By studying synaptic adhesion proteins, he broadened the understanding of brain functions and identified causes of brain disorders such as attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD), paving the way for improved disease treatments.
For his research on neural synapses, Kim received the 2018 ASAN Award in Basic Medicine, which recognized his significant contribution to Korea’s medical science development. In this interview with Asian Scientist Magazine, he described his ongoing pursuits and shared his hopes for medical research moving forward.
- How did you become interested in neuroscience research?
- You played a significant role in our current understanding of the formation and functions of synapses in the brain. Could you tell us how you figured out this complex problem?
- Please describe one interesting project that you are working on right now.
- Having come from a background of pharmacology and toxicology, what are your thoughts on drugs for the treatment of neurological diseases?
- What are your ambitions for the Institute of Basic Science’s Center for Synaptic Brain Dysfunctions?
- What do you think are some of the greatest challenges facing researchers in Asia today?
- How do you think these challenges can be overcome, and what changes do you hope to see?
- What advice do you have for early career scientists in Asia?
I received a bachelor’s degree in pharmacology. Because many drugs target the central and peripheral nervous systems, I became increasingly interested in the brain and how drugs work to alleviate various brain dysfunctions.
At that time, the introduction of the yeast two-hybrid system enabled us to identify the proteins that interacted with a protein of my interest. My group used the cytoplasmic tail of a synaptic potassium channel as bait and found that it interacted with PSD-95, which is an abundant synaptic scaffolding protein located beneath the synaptic plasma membrane.
PSD-95 later turned out to interact not only with various synaptic membrane proteins, such as neurotransmitter receptors, but also with diverse cytoplasmic signaling molecules. This finding critically linked synaptic receptor activation with downstream signaling pathways.
The findings made by my group and others provided an important view of the protein-protein interaction networks in the synapse and helped us understand how these protein-protein networks contribute to the formation, maintenance and plasticity of neuronal synapses.
Thanks to the rapid expansion of human genetic studies, many synaptic proteins have been associated with diverse neurodevelopmental and neuropsychiatric disorders, including intellectual disability, ASD, ADHD, schizophrenia and emotional disorders such as depression and bipolar disorder.
My group is currently focusing on ASD because there is no approved medication available to treat key symptoms, such as social deficits and repetitive behaviors. We are investigating the mechanisms underlying the development of ASD during embryonic and postnatal brain development using various approaches, including transgenic mouse models of ASD that lack genes known to be mutated in individuals with ASD.
A greater understanding of these mechanisms may help us to better understand ASD and develop efficient ways to diagnose and treat this important psychiatric disorder.
The known drugs for various brain dysfunctions are admittedly very useful, but unfortunately have many and serious side effects. The best way to develop drugs with fewer side effects would be to better understand the disease mechanisms.
Once we understand the basic functions of the molecules (i.e., proteins, RNAs and lipids) that are associated with neurological or neuropsychiatric disorders, as well as the exact pathophysiological mechanisms underlying certain brain disorders, we should be able to develop more efficient strategies to diagnose and treat these disorders.
I believe that high-quality basic sciences have great translational potential and are linked very closely to applied sciences, rather like the two faces of a coin. However, even the best drugs developed based on our most current understanding of the underlying mechanisms are likely to have significant side effects because of the highly complex nature of the nervous system.
Therefore, it may be necessary to use combinations of two or more drugs that can act together to alleviate multiple facets of a disease while minimizing the side effects seen when the drugs are given alone at higher doses.
We want to become a key contributor to the basic understanding of ASD and actively participate in fostering international cooperation among basic scientists, clinicians and patient groups to better understand and treat ASD.
Each country is trying its best and investing in efforts to boost basic and applied sciences. However, there seems to be a limited amount of international cooperation. I believe that researchers representing the various countries of Asia should, ideally in collaboration, develop systems to encourage and foster international collaborations.
The research directions in a given country are mainly (and understandably) determined by the domestic research communities. However, I feel that some resources should be allocated for international research collaborations, workshops and personnel exchanges. I would like to see the research proposals generated in each country contain aspects of international collaboration, which should be accounted for in the final evaluation of the research outputs.
We should also consider cooperating with scientists in Western countries to see if we can find interesting differences between Asian and Western populations. It is possible that the mechanisms or causes underlying certain brain disorders could be fundamentally different in the two populations, or that they are similar but lead to different symptoms or disease trajectories due to population-related differences in the relevant genetic backgrounds and epigenetic environments.
Young scientists are our hope. I would like to advise them to be more confident in themselves and dream about how much they could achieve in the future. They should also seek to communicate and establish solid networks with many bright international scientists to openly share exciting ideas and join forces in search of fundamental and critical findings.
This article is from a monthly series called Asia’s Scientific Trailblazers. Click here to read other articles in the series.
Copyright: Asian Scientist Magazine; Photo: Kim Eunjoon.
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