 |
Magdalena T. Tosteson, Ph.D.Lecturer on Cell BiologyDepartment of Cell Biology Phone: 617-621 6138 |
Magdalena Tosteson came to the Harvard Medical School in 1977, after a brief tenure in the Department of Physiology at the Pritzker School of Medicine, Chicago IL.
Research interests
Work in our laboratory is oriented to the identification, isolation and reconstitution of transmembrane proteins which play a role in ion transport across cellular membranes. The ultimate goal is to determine the functional properties of the molecule in isolation whilst embedded in a phospholipid membrane as well as to determine how these properties are changed by the addition of components known to interact with those proteins.
Research Projects
Reconstitution of the early steps in viral entry. Utilizing poliovirus as a model for viruses lacking a lipid coat, we were able to incorporate the full length poliovirus receptor in a lipid bilayer and demonstrate temperature-dependent changes in structure of the complex consisting of the virus bound to receptor, which are an important part of the entry process. This recapitulates the in vitro characteristics and paves the way for further studies on the residues which are important for entry, both from the virus side as well as from the side of the receptor.
Cellular determinants of poliovirus infection. In an attempt to further define the minimum requirements for infection, we started these studies by changing the cholesterol comtent of the plasma membrane of cells. We found that this did not modify binding of poliovirus but it did affect infectivity through the effect that the cholesterol-lowering drugs have on cellular systems. The continuation of this work has led to the use of libraries of cells containing siRNAs in order to determine the cellular components crucial in infection.
Effect of membrane potential on translation. We are starting to explore the effects that the membrane potential has on translation and on some of the cellular pathways involved in cell cycle progression.
Selected References
Tosteson MT, Nibert ML and Fields BN. 1993. Ion channels induced in lipid bilayers by subvirion particles of the nonenveloped mammalian reoviruses. Proc.Natl.Acad.Sci. 90:10549-10552.
Tosteson MT, Pinto LH, Holsinger LJ and Lamb RA. 1994. Reconstitution of the influenza virus M2 ion channel in lipid bilayers. J.Membrane.Biol. 142: 117-126.
Acosta JA, Benzaquen LR, Goldstein DJ, Tosteson MT and Halperin JH. 1996. The transient pore formed by homologous terminal complement complexes functions as a bidirectional route for the transport of autocrine and paracrine signals across human cell membranes. Molec Med. 2:755-765.
Tosteson MT and Chow M. 1997. Characterization of the ion channels formed by poliovirus in planar lipid bilayers. J.Virol. 71:507-511.
Magdalena T. Tosteson, Jae B. Kim, Daniel J. Goldstein & Daniel C. Tosteson. 2001. Ion channels formed by transcription factors recognize consensus DNA sequences. Biochimica et Biophysica Acta/Biomembranes 1510:209-218.
M. T. Tosteson, J.Thomas, J.Arnadottir and D.C.Tosteson. 2003. Effects of Palytoxin on Cation Occlusion and Phosphorylation of the (Na+,K+)-ATPase. J. Membrane Biol. 192:181-189.
Mayer Michael, Jennah K. Kriebel, Magdalena T. Tosteson and George
Whitesides. 2003. Microfabricated teflon membranes for low-noise recordings of ion channels in planar lipid bilayers. Biophys. J. 85:1-12.
Pranav Danthi, Magdalena Tosteson, Qi-han Li, and Marie Chow. 2003. Genome delivery and ion channel properties are altered in VP4 mutants of poliovirus. J.Virol. 77:5266-5274.
Tosteson Magdalena T., H. Wang, A. Naumov and Marie Chow. 2004. Poliovirus binding to its receptor in lipid bilayers results in particle-specific, temperature-sensitive channels. J. Gen Virol 85:1581-1589.
Liu S., Rodriguez A.V., and Tosteson M.T. Role of simvastatin and methyl-β-cyclodextrin on inhibition of poliovirus infection. Under review.
Personnel
Mika Matsuzaki
Updated: June 2, 2006