How “light-sensitive” proteins are being used to fuel scientific discovery | 25 – Brandon Berry

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Optogenetics is a cutting-edge field at the intersection of optics and genetics. This technique introduces microbial opsins, light-sensitive proteins naturally found in certain microorganisms such as algae and bacteria, into specific organelles, cells, or tissues to make them sensitive to light and thus precisely manipulable. Optogenetics has served as a powerful tool in neuroscience research, enabling scientists to dissect complex neural circuits and understand how they give rise to behavior, cognition, and disease; and is expanding its reach to other fields such as endocrinology, vision restoration, and muscle physiology.

In this episode, researcher Brandon Berry chats with Matt about the development and application of optogenetic tools to manipulate mitochondrial function in cells. He shares his experiences with engineering optogenetic proteins for mitochondrial targeting, the challenges involved in controlling mitochondrial charge, and the potential of optogenetics to manipulate mitochondrial membrane potential. He also discusses the complexities of mitochondrial dysfunction, the relationship between mitochondrial dysfunction and aging, and the role of mitochondrial membrane potential in longevity interventions, including caloric restriction.

Brandon, who is currently working on a stealth project, was a former postdoctoral research associate in Matt’s lab at the University of Washington, where he did a lot of his work on developing tools for mitochondrial control. He received a PhD in Physiology from the University of Rochester.

0:00 Trailer
1:12 Introduction
3:23 Brandon’s journey to his current career
7:42 How Brandon became interested in mitochondria + a primer on mitochondria
12:29 An introduction to optogenetics
14:02 The function of light-sensitive proteins
16:18 Optogenetic tools for mitochondria research
31:09 mtON and mtOFF tools and drugs
45:54 The mechanism by which mtOFF is protective
50:00 Applying these tools to geroscience research + the challenges of lifespan experiments
1:02:54 Mechanism by which mtON extends lifespan
1:04:08 How mtON affects NAD homeostasis
1:05:18 The effect of NAD precursors on mitochondrial membrane potential
1:06:33 Applying these experiments to other organisms
1:08:47 The relationship between caloric restriction and mitochondrial membrane potential
1:11:40 Relationships between mitochondrial membrane potential and other longevity interventions
1:13:27 Would curing mitochondrial dysfunction cure aging?
1:14:23 Potential applications of these tools in therapeutic and other settings

Producers: Tara Mei, Nicholas Arapis
Video Editor: Jacob Keliikoa

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Hi, I’m Matt Kaeberlein. I spent the first few decades of my career doing scientific research into the biology of aging, trying to understand the finer details of how humans age in order to facilitate translational interventions that promote healthspan and improve quality of life. Now I want to take some of that knowledge out of the lab and into the hands of people who can really use it.

On this channel I talk about all things aging and healthspan, from supplements and nutrition to the latest discoveries in longevity research. My goal is to lift the veil on the geroscience and longevity world and help you apply what we know to your own personal health trajectory. I care about quality science and will always be honest about what I don’t know. I hope you’ll find these videos helpful!

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