Home Faculty and Research Faculty by Name Ahmet Yildiz

Ahmet Yildiz

Assistant Professor of Biochemistry and Molecular Biology

Lab Homepage: http://physics.berkeley.edu/research/yildiz/

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Research Interests

One of the most fascinating features of biology is the directed movement of subcellular compartments and single proteins. While eukaryotes use muscle contraction for motion, enzymes can find their targeted molecule or location by random Brownian motion. However, cellular motility can be more demanding than what can be achieved by random diffusion, and the cell needs different means of transport to move organelles, chromosomes and sensors in a directed manner. This requires conversion of chemical energy into work. For example, duplicated chromosomes are moved to the metaphase plate before cell division through the rearrangement and polymerization of microtubule filaments. Synapses and dendrites can be far from the cell body of neurons and required receptor molecules and organelles are transported along the axons by the help of molecular motors moving along the microtubule.

These energy transducer enzymes are of great interest to biophysics and single molecule microscopy is an emerging field to study their mechanism. We now have tools in laboratory that can measure detect enzymatic events with one nanometer precision in space and sub-picoNewton sensitivity in force. Single molecule imaging has revolutionized our understanding in biology by direct observation of molecular motions, time courses of reactions and heterogeneity in subpopulations of the proteins. My research is focused on pushing the limits of sensitivity further by developing fluorescence and force clamp techniques. I aim to understand how macromolecular machines inside the cell work individually and how their interaction play a key role in cellular processes. We are also using superresolution imaging techniques to visualize cell cycle dependent changes in DNA structure.

Current Projects

The projects in the lab combine tools available in single molecule biophysiccs with molecular biology and biochemistry to understand the mechanism of complex enzymatic machinery in vitro and in living cells. Major focus is on cytoplasmic dynein motor, intracellular cargo transport, and chromosome end protection.

Dissecting the Molecular Mechanism of Dynein: Cytoplasmic dynein is a unique motor that transports a variety of intracellular cargo towards the microtubule minus-end in eukaryotic cells. However, a structural dissection of its mechanism has not been undertaken. By using budding yeast cells to genetically manipulate and express the dynein motor, we perform single molecule FRET experiments to measure interactions between the internal domains in an active protein and investigate how these interactions are correlated with the movement of the motor. The locations of the rings and their rotations will be detected by high spatial resolution two-color imaging and a polarization microscope as dynein walks along microtubules. These experiments will help us to draw a detailed mechanistic model of how dynein works in cells.

Single Molecule Studies on Intraflagellar Transport (IFT): To understand the mechanism of cargo transport in vivo, my lab is using Chlamydomonas cells as a model system. So far, we have tracked flagellar membrane proteins and observed that these proteins are transported uniformly toward a single direction. By using this system, we aim to understand how opposite polarity motors function together to move cargoes back and forth along the microtubules and how cells control their activity by associated enzymes. We use mutated strains of Chlamydomonas to externally control motor activity and manipulate cargo transport by applying forces via optical tweezers. Our studies will also reveal how cells can rapidly grow and maintain cilia and flagella by the help of these measurements.

Telomere Loop Formation: Telomeric DNA repeats protect ends of linear chromosomes against degradation. Because of the “3’-end replication problem”, telomeres constantly shorten upon each cell division and critically short telomeres lead to cell cycle arrest. Both aging and human cancers have been related to this important system. Although telomeres and telomere binding proteins have been extensively studied by genetic manipulations and biochemical methods, understanding the formation of functional telomere and its interaction with telomerase and other binding partners needs more sensitive measurements. We aim to develop a single molecule assay by reconstituting human telomere complex in vitro to observe how telomeres form loops for end capping of chromosomes and how these loops open and close as a replication fork reaches to the telomere. 

Selected Publications

Ahmet Yildiz, Michio Tomishige, Arne Gennerich and Ronald D. Vale. Intramolecular strain governs kinesin stepping behavior along microtubules. 2008. Cell 134,1.

Samara L. Reck-Peterson, Ahmet Yildiz, Andrew P. Carter, Arne Gennerich, Nan Zhang, Ronald D. Vale. Cytoplasmic dynein coordinates its two motor domains to move processively along microtubules. 2006. Cell 126, 335.

Ahmet Yildiz, Michio Tomishige, Ronald D. Vale, Paul R. Selvin. Kinesin walks hand-over-hand. 2004. Science 303, 676.

Ahmet Yildiz. How molecular motors move. 2006. Science 311, 792.

Ahmet Yildiz, Joseph N. Forkey, Sean A. McKinney, Taekjip Ha, Yale E. Goldman, Paul R. Selvin. Myosin V walks hand-over-hand: Single fluorophore imaging with 1.5 nm localization. 2003. Science 300, 2061.

Last Updated 2008-09-08