Microtubules are vital cytoskeletal polymers that play crucial roles in cell division, maintaining cell shape, intracellular transport, and cell motility. These biological functions are made possible through interactions with numerous microtubule-associated proteins (MAPs). However, recent advances in clinical genetics have uncovered many disease-related mutations in MAPs, whose mechanisms remain poorly understood. This gap in understanding inspired Dr. Eva Nogales, Senior Faculty Scientist at the UC Berkeley Lab, and Dr. Carsten Janke, leader of the research team “Controlling Microtubule Dynamics and Function with the Tubulin Code” at the Curie Institute in Orsay, France, to explore how MAPs coordinate microtubule functions to maintain cellular homeostasis. We had the privilege of speaking with Dr. Nogales to learn more about her academic journey, the motivations behind this collaborative project, and the opportunities afforded by the France-Berkeley Fund (FBF).
Can you introduce yourself and talk about your academic journey that led you to this project?
Eva Nogales: My name is Eva Nogales, and I’m originally from Spain, where I studied physics as an undergraduate. I eventually transitioned into the biophysical sciences, which brought me to England to study electron microscopy as a tool for visualizing biological samples. Later, I moved to the United States for my postdoctoral work at Lawrence Berkeley National Laboratory, where I collaborated with Dr. Ken Downing. Together, we used a specialized form of electron microscopy, electron crystallography, to determine the atomic structure of tubulin.
After completing my postdoc, I joined the faculty at UC Berkeley and continued my research on tubulin and microtubules. Over the years, this work allowed me to connect with Dr. Carsten Janke, who studies post-translational modifications of tubulin at the Curie Institute in France. When the opportunity to apply for funding through the France-Berkeley Fund arose, I immediately thought of Dr. Janke, as I knew our complementary expertise could lead to exciting collaborations.
What made you interested in microtubules and the tubulin code?
EN: I’ve always been fascinated by biological processes that are central to cellular life, and one of these is the cytoskeleton. The cytoskeleton is a network of polymers that provides structural support to cells, much like the skeleton does for the human body. It’s also critical for processes like cell movement and intracellular organization.
Microtubules, a key component of the cytoskeleton, are essential for organizing cellular contents. Without them, cells would become chaotic and non-functional. For instance, during cell division, microtubules are responsible for aligning and separating chromosomes, ensuring that each daughter cell receives a complete genome. They also play a role in flagellar movement, such as in sperm cells, where the microtubules in the tail generate the waves that propel the cell forward.
Their versatility is what makes microtubules so fascinating—they interact with numerous cellular components to carry out a wide range of functions. This complexity makes them a rich subject for study, providing opportunities to explore many facets of cell biology over a lifetime.
Could you elaborate on the focus of your research?
EN: Microtubules are indispensable for cellular organization, particularly in neurons, where their role becomes even more critical. Neurons have a central cell body, or soma, and long extensions called axons, which can span incredible distances—such as from your spine to your foot. Microtubules act as highways along these axons, enabling motor proteins to transport essential materials like synaptic transmitters.
When microtubule function is disrupted, it can lead to severe neurological issues. These may manifest as developmental disorders in early life or neurodegenerative diseases like Alzheimer’s later in life. My research focuses on understanding how chemical modifications to tubulin, the protein building block of microtubules, affect their ability to bind regulatory factors or motor proteins. Using electron microscopy, I visualize these interactions to uncover their structural and functional implications.
What were the key outcomes of your study?
EN: Our work aims to provide a molecular-level understanding of how cells, tissues, and organisms function. By studying the structure and behavior of proteins, we gain insights into the mechanisms underlying human diseases. This knowledge is critical for designing and improving therapeutic drugs.
Our research contributes to the foundational understanding of biological systems, offering clues to why diseases occur and how they might be addressed. For example, our structural studies of proteins provide a blueprint for drug development, helping to inform strategies to tackle diseases linked to microtubule dysfunction.
How has the France-Berkeley Fund supported your research?
EN: The FBF grant has been instrumental in facilitating collaboration between our labs. A significant portion of the funding has supported exchanges, allowing members of my lab to travel to Paris and work directly with Dr. Janke’s team. This opportunity for hands-on collaboration has generated valuable data and laid the groundwork for future projects.
The grant also provided a platform for exchanging expertise, methods, and perspectives, fostering a multidisciplinary approach. These interactions have been incredibly productive, sparking new ideas and potential research directions. The FBF has been a seed for scientific collaboration, opening doors for further exploration and innovation.
We extend our heartfelt thanks to Dr. Eva Nogales for taking the time to share her insights and the impactful work her team is conducting.