Focus

Molecular architecture and function of the microtubule cytoskeleton

Research

We are interested in understanding how cells acquire their shape, position organelles, move materials, and segregate chromosomes during cell division. These features are essential for life and organized by the microtubule cytoskeleton, which resembles the skeletal system that supports our human body. Each cell type and shape requires a specific microtubule architecture. For instance, long and bundled microtubules make up the axonal extensions of a nerve cell that can reach up to 1 meter in length, whereas a spherical microtubule network renders a lymphocyte perfectly round. In contrast to the human skeleton, the microtubule cytoskeleton is also highly dynamic. Most cells regularly undergo cell division, during which the cell-type specific interphase microtubule network is completely disassembled and replaced by short and dynamic microtubules of the mitotic spindle to capture, align and then segregate chromosomes.

How is a specific microtubule architecture established at the molecular level?

Microtubules are cylindrical and dynamic polymers that consist of the protein tubulin. The biological function of the microtubule cytoskeleton relies on the precise arrangement of microtubules in the cell. To achieve this organization, microtubule associated proteins generate, sever, polymerize, shrink, bundle, anchor, or move microtubules. We want to understand these functionalities mechanistically and use this insight to explain how they ultimately result in the self-organization of the microtubule cytoskeleton.

We employ two complementary approaches that allow us to both look at structural detail of microtubule effectors and explain their function in the biological context. To study the mechanism by which microtubules are organized at a structural level, we use biophysical methods, electron microscopy and X-ray crystallography. To understand the dynamic assembly of the microtubule cytoskeleton, we combine biochemical and cell biological techniques along with advanced light microscopy methods.

Our goal is to identify and characterize new mechanisms that establish the cellular microtubule architecture. This will ultimately reveal how the microtubule cytoskeleton builds cellular structures to give cells their shape, position organelles, serve as tracks that move materials, generate force for movement, and segregate chromosomes.

Biography

Sabine Petry, Ph.D is originally from Germany and studied Biochemistry at the Goethe University, where she became interested in structural biology. She performed her Master’s thesis at the Max Planck Institute of Biophysics in Frankfurt under supervision of Prof. Carola Hunte and Prof. Hartmut Michel (Nobel Prize Chemistry 1988). Sabine performed her thesis research with Dr. Venki Ramakrishnan (Nobel Prize Chemistry 2009) at the MRC Laboratory of Molecular Biology (UK) from 2003 - 07. She was involved in solving the first crystal structure of a classical translation factor bound to the entire ribosome, work that helped increase our knowledge of how translation factors drive protein synthesis in the ribosome.

In 2008, Sabine joined Ron Vale's lab at UCSF as a postdoctoral HHMI Fellow of the Life Science Research Foundation, where she pursued the study of a less understood and larger molecular entity, the mitotic spindle. Her research focused on understanding how microtubule nucleation is regulated in the mitotic spindle, which is poorly understood. It led to the discovery of a new microtubule nucleation mechanism, in which microtubules arise by nucleation from existing microtubules. Branching microtubule nucleation helps explain many unresolved aspects of how the mitotic spindle is assembled, and raises new questions about its role in building the microtubule cytoskeleton of the cell.

The Petry Lab was inaugurated in 2013 and combines high-resolution microscopy methods along with structural studies to study how the microtubule cytoskeleton builds cellular structures. Sabine received the NIH Pathway to Independence Award, the Kimmel Scholar Award for Cancer Research and the Packard Fellowship for Science and Engineering. She is also a Pew Scholar in the Biomedical Sciences.

Honors & Awards