University of Dundee Inke Näthke Sedwick, C.; Nathke, Inke Published in: Journal of Cell Biology DOI: 10.1083/jcb.1895pi Publication date: 2010 Document Version Publisher's PDF, also known as Version of record Link to publication in Discovery Research Portal Citation for published version (APA): Sedwick, C., & Nathke, I. (2010). Inke Näthke: The ABCs of APC. Journal of Cell Biology, 189(5), 774-775. https://doi.org/10.1083/jcb.1895pi General rights Copyright and moral rights for the publications made accessible in Discovery Research Portal are retained by the authors and/or other copyright owners and it is a condition of accessing publications that users recognise and abide by the legal requirements associated with these rights. • Users may download and print one copy of any publication from Discovery Research Portal for the purpose of private study or research. • You may not further distribute the material or use it for any profit-making activity or commercial gain. • You may freely distribute the URL identifying the publication in the public portal. Take down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Download date: 01. Oct. 2021 Published May 31, 2010 People & Ideas Inke Näthke: The ABCs of APC Näthke investigates the many functions of adenomatous polyposis coli protein and its contribution to human disease. ighty percent of human colon can- I wanted to go to a foreign country, to cers carry a mutation in adenoma- experience a different way of life, and E tous polyposis coli (APC) protein. the easiest way to do that was to become APC is an adaptor protein that helps regu- an au pair. So I wrote to newspapers in late the cytoskeleton and also modulates the Ireland, and I looked for jobs in New behavior of signaling proteins like ␤-catenin. Zealand. I wasn’t really looking to go to Inke Näthke is working to understand the United States, but a friend of my father’s APC’s normal functions in cells, and why helped me fi nd a place with a family in APC mutations are so frequently associated San Jose, California. The family was with cancers of the gut (1–5). wonderful. They welcomed me into their As a graduate student studying the home and I fell in love with California. Downloaded from structure and function of clathrin in I was supposed to go home after a year Frances Brodsky’s lab at UCSF (6), but when the time came, I didn’t want to Näthke was focused on biochemistry and leave. By that time, too, I had discovered her lab mates teased her for working exclu- the college system in the States, which sively with purifi ed proteins. But as a compared to the one in Germany was postdoc in James Nelson’s lab at Stan- very open-ended; you didn’t have to declare ford, Näthke made the discovery that a major right away. I thought that sounded jcb.rupress.org would shape her career through the lens perfect for me. of a microscope: a striking and unusual Inke Näthke interaction between APC and the micro- So you went to college in the States? tubule cytoskeleton (7). It turned out I had to go back to Germany Her interest piqued by that initial for a year to get some academic prerequi- SERENDIPITY observation, Näthke has uncovered new sites out of the way, but I fi nally enrolled What made you decide to pursue a on May 31, 2012 secrets about APC ever since. We called at San Jose State University as a premed graduate degree? her at her laboratory at the University of student. I quickly decided that wasn’t for In the end what really interests me is the Dundee in Scotland to dis- me, partially because I had idea of applying chemistry and biology cuss how APC affects cell discovered biochemistry to questions related to human disease. I biology, tissue architecture, “What and decided that was fas- didn’t recognize that at the time, but and her career. interests me cinating. After college, I looking back, I see that most of the deci- is the idea was again supposed to go sions I’ve made were guided by that. In CHOICE back to Germany. I even fact, I’m currently helping to set up a Where did you grow up? of applying had a one-way airplane new cancer center here in Dundee, so In Germany. I stayed there biology to ticket ready to go, but I I’m able to pursue that interest more di- until the end of high school. questions called and cancelled it. That rectly. But at the time, I just felt that I had the blessing—or maybe felt, even at the time, like there were many interesting questions it was a curse—of being related one of those major life- out there that I could work on. I wasn’t pretty good at many differ- to human altering decisions. If I hadn’t driven by any particular problem. ent things. I was good at disease.” stayed, I would not have I did my graduate work with Frances languages. I enjoyed math, been in the same environ- Brodsky, where I worked on clathrin chemistry, and music. As a ment or met the people who structure and function. That work—and result, I didn’t really know what I wanted helped me get to where I am today. But I just being at UCSF, where cell biology to do for a career. If I’d gone to college did stay, and I worked for a year as a tech- was really coming into its own—intro- immediately after high school, I’d have had nician with a small biotech fi rm in the Bay duced me to a lot of cell biology–related to choose a particular subject to study, but Area. I hadn’t really decided what I wanted questions. When the time came to decide I didn’t feel ready to make that choice. to do next, but while I was at that company, on a postdoctoral position, I spoke to a Fortunately, my parents were understanding, I heard about the pharmaceutical chemistry number of different people, and in the end and when I said I wanted to take some time program at UCSF. I decided to enroll as a I joined James Nelson’s lab at Stanford to off before college, they supported me. graduate student there. work on cell adhesion. 774 JCB • VOLUME 189 • NUMBER 5 • 2010 Published May 31, 2010 Text and Interview by Caitlin Sedwick [email protected] part of the Wnt signaling pathway, and plays a role—recently it’s even cropped for the connection that has to cancer. But up in DNA repair and in hypoxia. We’re that’s not all there is to APC. It’s an adap- now picking apart whether these are di- tor protein, so it has its fi ngers in a lot of rect or indirect links. We’re trying lots of different pies in the cell, but it turns out new biochemical assays to look at APC’s that it isn’t absolutely needed for any- interactions with other proteins, and using thing it does. You can knock it out and fl uorescent probes to explore these inter- nothing dramatic happens. Cells that lack actions in cells. APC still move and grow, and although One of our goals is to explore how they don’t differentiate as well, they can APC’s interactions with its partners are still divide. The fi delity of mitosis is de- regulated. An increasingly important as- fective, so cells make more pect of our work is to look mistakes. But these mis- at whole tissue physiology takes are tolerated, and the “APC has and whole tissue architec- cell can keep growing and its fingers ture to see whether the Downloaded from Seeing APC (green) on microtubule (red) ends proliferating. But without changes we see in cells in sparked Näthke’s curiosity. in a lot of APC, all these processes Petri dishes translate into are slightly off-kilter; all different pies changes in gut tissue. We It was during your postdoc that you fi rst these little errors push the in the cell.” are even starting to explore, encountered APC? cell just that much closer to using a computer modeling That was serendipity—I just happened to having a real problem—to approach, how mutations be in the right place at the right time. I had becoming cancerous. All you need is one in APC affect the mechanical properties jcb.rupress.org been working with a graduate student in more nudge in that direction for the real of gut tissue. It feels like a lot of work James’ lab on the interaction between cat- trouble to start. and my lab is pretty small, but I have a enins and cadherins. We’d made some anti- We think this is why you see APC really talented and dedicated group of bodies to catenins, in particular ␤-catenin, mutations so frequently in colon cancer. people who help shape each step in the because catenins had just been discovered The intestine is not a friendly environ- work we’re doing. I love going to work and there weren’t many good antibodies ment; gut epithelial cells only last about in the morning. on May 31, 2012 around at the time. One day, Paul Polakis fi ve days so they must be continually 1.