Cell surface receptors are, by and large, the main molecular target for therapeutics. Also known as transmembrane receptors, they’re the targets of more than 60% of drugs today. But scientists are still trying to understand these receptors and their potential to illuminate human biology and advance clinical treatments.
Join us at IPI Surfacing!
Junichi Takagi, a professor at Japan’s Osaka University, knows this well. His research uses structural insights to elucidate cell signaling mechanisms, with a particular focus on receptor-ligand interactions involved in immunology and neuroscience. His findings could improve gene therapy vectors using adeno-associated viruses, uncover pathways involved in embryonic patterning and cell development and help develop treatments for myasthenia gravis and other neuromuscular diseases.
This June, Takagi will join other leading protein scientists at IPI Surfacing, a symposium on cell surface receptor biology hosted by the Institute for Protein Innovation (IPI) at Harvard Medical School, to delve into recent advances in biomedical research.
Ahead of Surfacing, we asked Takagi about his research, his motivations in the lab and the future of cell surface receptor biology. His answers are below, edited for length and clarity.
Q: In your experience, what makes cell surface receptors difficult targets to work with?
Takagi: Purifying them from cell extracts is easy, but reconstituting them in a lipid bilayer with intact function and structure is not. That’s why I mostly work with the ectodomain fragment of transmembrane receptors, which are no different than secreted proteins.
Q: What is the biggest challenge facing cell surface receptor biology right now?
Takagi: Cryo-electron microscopy technology is so advanced, and it is easy to derive seemingly OK three-dimensional structures for receptors, even with a limited amount of protein science skills. People are beginning to think that protein experts are no longer needed.
On the contrary, young experts with good eyes for inspecting protein structure and their biochemical and biophysical behaviors are becoming more important in the era of AlphaFold 2.
Q: What will the field look like in 10 years? Where’s the next big breakthrough, in your opinion?
Takagi: I want to see a quantum leap in the resolution and applicability of high-speed atomic force microscopy so that we can see a receptor dancing (and catching the ligand!) on the membrane in real time.
Q: Was there a moment that cemented your interest in protein science?
Takagi: Moments like these are hard to forget: when I saw the chromatographic separation of beautifully blue ceruloplasmin out of dull-color concentrated plasma during my undergraduate lab experiments; when I confirmed specific binding of 125I-labeled platelet protein to collagen in Scatchard analysis for my Ph.D. thesis; or, when I saw an image of α5β1 integrin in the rotary-shadowed transmission electron microscopy specimen looking like the “Dancing Men” in Sherlock Holmes’ book at the Springer lab.
Q: What is the big-picture goal of your research?
Takagi: I want to see my protein science expertise contribute directly to the development of therapies and drugs to save the lives of children suffering from rare — or any — diseases.
Source: Junichi Takagi, takagi@protein.osaka-u.ac.jp
Writer: Caitlin Faulds, caitlin.faulds@proteininnovation.org
About the Institute for Protein Innovation
The Institute for Protein Innovation is pioneering a new approach to scientific discovery and collaboration. As a nonprofit, we provide the biomedical research community with synthetic antibodies and deep protein expertise, empowering scientists to explore fundamental biological processes and pinpoint new targets for therapeutic development. Our mission is to advance protein science to accelerate research and improve human health. For more information, visit proteininnovation.org or follow us on social media, @ipiproteins.