Research Interests

Potassium transport by the KdpFABC complex

KdpFABC is a membrane complex that is expressed in many bacteria under low potassium conditions. It uses ATP to actively pump potassium into the cell, thus maintaining intracellular homeostasis and turgor. The complex represents a unique collaboration between a pump subunit that belongs to the P-type ATPase superfamily and a channel subnit that belongs to the Superfamily of Potassium Transporters (SKT). We have solved a crystal structure that sheds light on the novel mechanisms of energy coupling between these subunits. Read more

Zinc transport of the secondary transporter YiiP

YiiP is a Zn2+ transporter belonging to the Cation Diffusion Facilitator (CDF) family. We have used helical reconstruction and cryo-EM to solve an atomic structure of this transporter. We have also used cystein substitution to form intermolecular and intramolecular crosslinks, which combined with in vitro functional assays and structural information, shed light on the conformational changes that give rise to transport. Read more

 

Older Projects

CopA is an ATP-dependent Cu+ pump belonging to the family of P-type ion pumps. We used methods of helical reconstruction to solve 3D structures of three different crystal forms of CopA. These structures have allowed us to address the role of the N-terminal domain in regulation of this pump. Read more

As part of the Transcontinental EM Initiative for Membrane Protein Structure, we have been developing technologies for producing and analyzing two-dimensional crystals. Read more

Electron Tomography

Red blood cells are characterized by a specialized cytoskeleton that confers remarkable flexibility to the cell. We have used cryo-electron tomography to visualize the 3D topology of the spectrin network that underlies this skeleton and collaborated with mathematicians to model the behavior of the skeleton under shear stress. Read more

Cardiolipin is a specialized lipid found exclusively in the inner membrane of mitochondria. Defects in the synthesis of cardiolipin lead to the mitochondriopathy, Barth syndrome. We have used electron tomography to characterize morphological defects to mitochondrial cristae as well as abnormalities in the distribution of ATP synthase caused by a deficit in cardiolipin. Read more

An adaptive immune response is initiated when naive T-cells recognize a specific antigen on the surface of an antigen presenting cell. We have been studying this process using electron tomography and have discovered a surprising release of vesicles at a specialized zone at the intercellular interface. Read more

Phi12 is a bacteriophage belonging to the family of cystoviridae. It is an enveloped virus with a multi-shell structure that is analogous to members of the Reoviridae family. We have used cryo-electron tomography and sub-tomogram averaging to analyze the 3D structure of the surface glycoprotein responsible for host recognition and infection. Read more