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Anne Delcour
University of HoustonDepartment: Biology & BiochemistryAddress: 369 Science & Research Bldg II Houston, TX 77204-5001 Phone: 713-743-2684 Fax: 713-743-2636 Email: adelcour@uh.edu Web: www.bchs.uh.edu/people/faculty/research-divisions/index.php?155622-961-5=biolcc |
Education
B.S. Zoology, University of Liege (Belgium) (1981)
Ph.D. Biochemistry, Cornell University (1986)
Univ. Wisconsin-Madison (1986-1990); Stanford University (1990-1992)
Honors
Nominated for Chair of the 2002 and 2004 Gordon Conference on Bacterial Cell Surfaces
Faculty Development Award, Natural Sciences and Mathematics Alumni Association, University of Houston: 1997
Travel award from the Biophysical Society: 1996
Junior Faculty Enhancement Award, Oakridge Association of Universities: 1994
NIH postdoctoral fellowship (NRSA): 11/1/90 - 7/31/92
NIH traineeship from the Department of Medical Genetics (University of Wisconsin-Madison): 1/1/1989 - 1/31/90
Muscular Dystrophy Association fellowship: 1/1/1987 - 12/31/1988
International Fellowship from the American Association of University Women: 9/1/1982 - 8/31/1983
Research Topic
Molecular mechanisms of bacterial ion channels
Research Description
I am interested in the molecular mechanisms of ion channel function and modulation. In particular, my lab is focused on the study of bacterial ion channels because bacteria are a convenient system where electrophysiological, biochemical and genetic studies can be performed. We use the patch clamp and planar lipid bilayer techniques to measure the electrical activity of single channel proteins in real time. The computer analysis of the data gives us information on the size and selectivity of the ion channel, kinetic properties, dependence on transmembrane voltage or on other physical or chemical parameters, and mechanisms of modulation.
We are in the process of characterizing the molecular properties of various channels from Escherichia coli and Vibrio cholerae (the agent of cholera). Most of our effort is devoted to our NIH-funded study of porins, abundant channels of the outer membrane. These proteins play an essential role in the survival of the cell, and their study is of great interest not only in the broad scope of fundamental research on ion channels and bacterial physiology, but also with respect to potential medical applications. Our goal is to understand the molecular mechanisms underlying gating and modulation of these ion channels. They are one of the few ion channels whose structure is known at atomic resolution. This gives us the excellent opportunity to investigate the relationships between structure and function by performing electrophysiological and biochemical experiments on both spontaneously occurring and genetically engineered mutant channels. We use a variety of approaches in the study of the molecular properties and modulation of the porins of Escherichia coli and Vibrio cholerae, including electrophysiology, bacterial genetics, molecular biology, ESR and fluorescence spectroscopy.
Unlike eukaryotic channels, porins are barrels made of 16 beta-strands spanning the membrane and connected to each other by extracellular and periplasmic loops. One of these loops (L3) folds back inside the pore and forms the channel's constriction zone. We have found that mutations of various residues around the constriction zone - on L3 and in the barrel - have different effects on the channel gating kinetics. This suggests that this loop might be involved in the conformational changes responsible for the fluctuations of the channel between open and closed states. We are continuing our studies of structure-function relationships by using site-directed mutants and engineered proteins to identify the role of extracellular loops in voltage- and pH-dependence. Current and future projects involve electrophysiological and spectroscopic methods to gain information on the dynamic properties of the wild-type and engineered channels.
We are also studying the modulation of porins by naturally occurring chemicals, such polyamines and bile. We have demonstrated that some porins are inhibited by these compounds in patch-clamp experiments and antibiotic flux assays. Current projects include the isolation and characterization of porin mutants that have lost sensitivity to this inhibition. The analysis of these mutants will provide us with insights into the inhibitory mechanisms, and will allow us to delineate the physiological relevance of these forms of modulation.
Additional interests of the laboratory deal with other pore-forming proteins, such as porins from other bacterial species, bacterial homologs of eukaryotic channels, and pore-forming toxins from bacterial pathogens.
Selected Publications
- Lauman, B., Pagel, M. and Delcour, A. H., “Altered Pore Properties and Kinetic Changes in Mutants of the Vibrio cholerae Porin OmpU”, Molec. Membr. Biology 25:489-505 (2008)
- • Duret, G., Szmanski, M.., Choi, K.-J., Yeo, H.-J., and Delcour, A. H., “The TpsB Translocator HMW1B of Haemophilus influenzae Forms a Large-Conductance Channel”, J. Biol. Chem. 283:15771-15778 (2008).
- Duret, G., Simonet, V. and Delcour, A. H., “Modulation of Vibrio cholerae Porin Function by Acidic pH”, Channels 1:70-79 (2007).
- Duret, G. and Delcour, A. H., “Deoxycholic Acid Blocks Vibrio cholerae OmpT but not OmpU Porin, J. Biol. Chem. 281:19899-19905 (2006).
- Baslé, A., Qutub, R., Mehrazin, M., Wibbenmeyer, J. A. and Delcour, A. H. (2004) Deletions of Single Extracellular Loops Affect pH-Sensitivity, but not Voltage-Dependence, of the E. coli Porin OmpF, Prot. Engineering Design and Selection, 17:665-672.
- Baslé, A., Iyer, R. and Delcour, A. H.(2004) Subconductance States in OmpF Porin Gating, Biochim. Biophys. Acta, 1664:100-107.
- Delcour, A. H. (2003) Solute Uptake through General Porins. Front. Biosci. 8, d1055-1071. URL:http://www.bioscience.org/2003/v8/d/1132/fulltext.htm
- Simonet, V. C., Basl�, A., Klose, K. E. and Delcour, A. H. (2003) The Vibrio cholerae Porins OmpU and OmpT Have Distinct Channel Properties. J. Biol. Chem. 278: 17539-17545.
- Liu, N., Samartzidou, H., Lee, K.-W., Briggs, J. and Delcour, A. H. (2000) Effects of Pore Mutations and Permeant Ion Concentration on the Spontaneous Gating Activity of OmpC Porin. Protein Engineering 13:491-500.
- Iyer, R., Wu, Z., Woster, P. M. and Delcour, A. H. (2000) Molecular Basis for the Polyamine - OmpF Porin Interactions: Inhibitor and Mutant Studies. J. Mol. Biol. 297:933-945.
Lab Members
Current Graduate Students
Former Grad Students
Former Post Docs
Lab Photos
Last edited on: September 21, 2009