Ahead of our 2022 Virtual KAND Family & Scientific Engagement Conference on August 13, 2022, KIF1A.ORG interviewed core KIF1A Research Network members to discuss their #relentless efforts to understand KIF1A and help KAND patients in this special “Meet the Research Network” series on the KIF1A.ORG blog.
KIF1A.ORG’s Research Engagement Director Dylan Verden, PhD, had the pleasure of talking with Kumiko Hayashi, PhD, associate professor of Applied Physics at Tohoku University. Dr. Kumiko discusses her work modeling the number of KIF1A molecules that cooperate to carry cargo.
Dr. Hayashi: Hi I’m Kumiko Hayashi from Japan. I’m Associate Professor with Tohoku University. So a lot of people related to KIF1A research are biologists, but in my case I’m a physicist. I learn physics and I got a degree in the physics area. It’s quite rare I think. In my case, from the viewpoint of physics, I’d like to contribute to this organization because the physical measurements inside cells are very difficult usually. I’d like to develop new physical measurement methods to analyze axonal transport by kinesins.
Dylan: Do you have any messages to the KIF1A community about why you decided to pursue this rare disease research?
Dr. Hayashi: From the first, honestly speaking, because I’m a physicist, I was interested in transport phenomenon such as electric current and heat conductivities, so these are the subject of physics. My colleagues told me there is transport inside our bodies. My colleagues told me about axonal transport in neurons. I think because I studied physics of transport phenomenon, so I can contribute this technique and knowledge to axonal transport. After that, my colleagues, coworkers, collaborators, told me that this is a very heavy disease related to this axonal transport. I am very interested in it. My friend and my sister has a kind of neuronal disease. It has become very motivating for me.
Dylan: What about kinesins are you trying to learn more about? What about the way that they carry cargo is important to better understand?
Dr. Hayashi: It is known that one synaptic cargo is transported by multiple kinesins recently. It was found that many motors carry one cargo together. It’s like ants carrying candy or something sweet, together. In my case, what we investigate is to count the number of motor proteins/kinesins carrying one cargo. We’d like to measure the number of motor proteins carrying a cargo. We think this number is very important, because when the number of kinesins decreases, the axonal transport becomes inefficient. At the same time, when the number of motor proteins/kinesins increases rapidly, probably axonal transport becomes abnormal. So I think there is an appropriate number of kinesins together carrying a cargo, and we’d like to check that.
Dylan: How does this relate to KIF1A mutations that might occur in KIF1A-Associated Neurological Disorder?
Dr. Hayashi: It is known that one mutation in KIF1A causes abnormality in autoinhibition mechanisms. Usually, there are appropriate numbers of KIF1As carrying synaptic cargoes. If there is a deficit in autoinhibition mechanisms of KIF1A, there are many active KIF1A motors inside neurons. In that case, many synaptic cargoes are transported abnormally. In this case, the synaptic formation becomes abnormal because of this active transport, abnormal transport. So we think we’d like to investigate it quantitatively, this abnormal active transport which is caused by deficits of autoinhibition mechanisms in KIF1A.
Dylan: Is there anything else you’d like to share with the KAND community?
Dr. Hayashi: Physicists also like to help people. Usually, medical [people] think that this is not our subject, but if we have the opportunity, we are very happy to contribute to the organization and I am very appreciative that you give us the opportunity to contribute our technique.