¡Post-Doctoral Positions Open Immediately (June 2009)!

Teresa Ruiz, Ph. D.

Associate Professor

Department of Molecular Physiology & Biophysics

HSRF Building, Room 106

149 Beaumont Avenue

Burlington, VT 05405, U.S.A.

Tel: +1 (802) 656-4835

Fax: +1 (802) 656-0747

truiz@physiology.med.uvm.edu

A strong correlation exists between structural properties and functional mechanisms of macromolecular complexes. Our goal is to understand the structural/functional relationships of macromolecular complexes using high resolution electron microscopy and image processing techniques. Our results combined with atomic resolution X-ray data using hybrid or multiresolution techniques and with the available biochemical and biophysical data will provide a better understanding of the functional mechanism of biological systems. Presently our main interests are focused on two areas, energy metabolism and bacterial adhesion.

I. Structure/function studies of eukaryotic phosphofructokinases and their interaction with the cytoskeleton

Glycolysis and respiration are the main pathways for energy production in living cells. Although respiration is mostly favored by multicellular organisms, muscle and cancer cells behave more like unicellular organisms using glycolysis as their main energy pathway. Deficiencies and dysfunction of glycolytic enzymes, in particular phosphofructokinase (Pfk), results in severe clinical syndromes and diseases (e.g., Hemolytic anemia, Tauri's disease, non-insulin dependent diabetes mellitus). Pfk plays a key role in the regulation of the glycolytic pathway and its activity, in eukaryotes, is controlled by a large number of allosteric effectors (~20). During the past twenty years, large efforts have been devoted to comprehend the mechanisms of catalysis and regulation of Pfk. However, the structures of the eukaryotic enzymes are still largely unknown, in most cases due to the lack of good quality crystals for X-ray analysis.

We are analyzing the structure of Pfk from eukaryotic organisms (S. cerevisiae, S. pombe) in the presence of different combinations of effectors and substrates by novel techniques of cryo-electron microscopy of single particles and image processing, and by fitting X-ray models to the electron microscopy structures. These studies will provide significant new information regarding the structure/function relationship of the mechanism of catalysis and regulation of phosphofructokinase in eukaryotic organisms. more...>

II. Structure of oral bacterial adhesins and adhesin/receptor complexes

Oral bacteria not only can cause severe periodontal diseases but, as opportunistic pathogens, have been associated with other serious human infections (e.g., endocarditis, pneumonia, vertebral osteomielitis, atherosclerosis). Bacterial colonization and subsequent invasion are usually preceded by bacterial adhesion to host cells. Adhesion is mediated by fimbriae or other proteinaceous appendages found on the cell surface of gram-positive and gram-negative bacteria.

We are studying two major colonizers of the oral cavity as model systems, S. parasanguis and A actinomycetemcomitans. In S. parasanguis , a gram-positive bacteria, cell host adhesion is mediated by fimbriae, specifically by the fimbriae-associated adhesin (Fap1) and in A. actinomycetemcomitans, a gram-negative bacteria, adhesion to the host extracellular matrix is mediated by antenna-like appendages of a single bacterial protein (EmaA). Through a combination of several electron microscopy techniques (negative staining, vitreous ice, tomography, single particles ...) with biochemical and molecular genetic techniques. We are trying to unveil the structure of the external appendages, their anchorage to the bacterial membrane and their interaction with the various human cell host components. The final goal is to extrapolate the findings on these model systems to other pathogens with similar mechanisms of adhesion and invasion. more...>

last updated October 2008