Ahmet Yildiz is a professor in the departments of Molecular & Cell Biology and Physics. The Yildiz laboratory combines biochemical and single-molecule biophysical techniques to understand how motor proteins move on microtubules long distances at fast speeds and produce the forces required to carry their cargo in a dense cytoplasm.
QB3-Berkeley: Are there any recent papers or breakthroughs in your lab that you’re particularly excited about?
Ahmet Yildiz: There are a few. We just started working on a group of proteins called structural MAPs, which stands for microtubule-associated proteins. These proteins bind to the microtubule filaments inside the cell, and their main job is to stabilize and organize the microtubule network, especially in neurons. However, recent studies show that they also regulate the intracellular transport of motor proteins that walk along these linear tracks, which is my main interest.
We don’t know exactly where these MAPs bind on the microtubule or how they interact with trespassing motors. Many researchers study this problem at different levels, such as examining where MAPs decorate microtubules in neurons and how their abundance affects transport. We, however, want to take a bottom-up approach. Together with the Eva Nogales lab, we determine where MAPs bind on the microtubule filament by solving their microtubule-bound structure using cryo-electron microscopy. Then, we reconstitute the motility of motor proteins on microtubule filaments immobilized on the glass surface. We introduce motors with labels and decorate microtubules with MAPs to see how the presence of a MAP affects motor movement. Through these experiments, we discovered that most MAPs inhibit motor-driven transport by binding to the same place on the microtubule, making it more crowded and affecting motor binding.
A special MAP called MAP7, however, appears to be a required cofactor for kinesin-1, the most abundant kinesin in cells. Without MAP7, kinesin doesn’t bind to the microtubule, so it is essential for kinesin activation and cargo transport. Interestingly, both kinesin-1 and MAP7 bind to the same site on the microtubule, which was unexpected since an activator typically doesn’t compete for the same binding site. We found that MAP7 boosts kinesin-1 transport by interacting with kinesin away from the microtubule surface. This interaction rescues kinesin from autoinhibition and helps it avoid obstacles as it moves along the microtubule. Through high-resolution tracking of kinesin motors on MAP7-decorated microtubules, we developed a model for how MAP7 facilitates kinesin-driven transport despite this overlap.
QB3: How do you stay motivated and inspired in the face of research setbacks or challenges?
AY: Scientists face many setbacks and challenges daily. I tell my students: Experiments often fail. If everything worked right away, we’d quickly get the answers we wanted, move on to the next problem, and keep troubleshooting.
However, despite the setbacks, we also have moments of success when experiments work, and we address the questions we have been searching for. I stay motivated because I like being challenged and trying to solve problems. I enjoy working on issues that interest me, and I have the freedom to decide which problems to tackle. This intellectual freedom and the pursuit of nature’s mysteries make me enthusiastic to come to the lab every morning. I find research intellectually rewarding, and I think of it as a unique privilege. Throughout history, those who’ve made lasting contributions were philosophers and scientists—not politicians—which motivates me to contribute to science, even if in a small way.
QB3: Could you share an experience from your early life that sparked your interest in science?
AY: I grew up in a rural area in Turkey, where most people worked on farms or in factories and few had a college education. My parents, for example, had little schooling and I’m the youngest of seven. My elementary school teacher, however, sparked my interest in math and science. He assigned me projects—simple things like studying rocks and fieldwork—that went beyond our curriculum. I enjoyed focusing on these projects and delving into the details rather than learning superficially and moving quickly to the next topic. This experience made me realize that I preferred depth, rather than breadth in my studies. Despite not coming from a family of scientists, I met people who guided me in the right direction, and I eventually attended a challenging science high school in Turkey, where I decided to pursue a career in science.
QB3: What is your teaching philosophy, and how do you engage students in science?
AY: I enjoy teaching in the classroom, but I am especially passionate about training graduate students in research. I meet with each student as much as they need, ensuring they understand the significance of our work, what’s known, and what we aim to achieve. It takes time for young researchers to see the big picture, so I try to provide that perspective rather than just assigning experiments. I want them to understand the context of their projects and feel part of a bigger scientific community.
It takes time for a new graduate student to become fully independent in the lab. I closely supervise newly joined students and assign senior students or postdocs to provide them with hands-on training as much as they need. Once the student becomes autonomous, I emphasize that each project is the student’s intellectual property. I tell them to think of their research as their mini startup. This sense of ownership is crucial because research is not a nine-to-five job. It requires dedication, learning, and perseverance in the face of failure. A sense of ownership is essential for a researcher to become more motivated to overcome challenges and succeed.
QB3: Can you share a story about a student who has gone on to do something remarkable?
AY: I have had a chance to work with many spectacular students, which is definitely one of the most significant perks of being a faculty member at Berkeley. I can perhaps highlight one of my first Biophysics students, Vladislav Belyy, who graduated in 2014. At the time I joined Berkeley as a young assistant professor, many of the microscopes we used weren’t commercially available, so we had to build them using hundreds of parts from different vendors. Vlad was truly exceptional in instrumentation, optics, programming, electronics, and biophysics. He built half of our lab’s equipment, and we still use some of his microscopes today. His contributions were crucial for the success of my lab when we first started.
Vlad has also made significant discoveries, such as showing how dynein’s two legs work together to pull against piconewton-scale forces in the cell. He also developed a new microscopy method to track single molecules in the crowded environment of the cell. He went on to work with Peter Walter at UCSF on ER stress sensor activation. He is now an assistant professor at the Ohio State University, combining biophysical techniques with cell biology to study stress sensor activation in cells. His skills and contributions have made him a remarkable researcher, and I’m quite excited about the ongoing research in his lab.