people
|Faculty
|Megan Spence
 |
Megan Spence Department of Chemistry |
Professor Spence's research focuses on peripheral and integral membrane proteins with nuclear magnetic resonance (NMR) techniques. Although one third of eukaryotic proteins are membrane proteins, only a handful have been structurally characterized, putting membrane-associated proteins at the frontier of structural biology. The partly-ordered nature of these membrane-associated systems requires us to develop new NMR techniques for systems at the solids / liquids interface as well as employing existing solid-state and solution-state NMR techniques.
Questions we can ask about these proteins / membrane systems include:
- What is the structure of the protein on the membrane?
- What is the orientation of the protein with respect to the membrane?
- What are the dynamics of the protein on the membrane?
- How does the protein affect the membrane structure and dynamics?
Professor Spence is interested in a group of neurotoxins isolated from tarantula venom whose mechanism of toxicity involves inhibiting transmembrane ion channels. Recent work by Lee and MacKinnon1 has shown that the neurotoxin, a small water-soluble protein, actually dissolves in the hydrophobic lipid bilayer and may affect the ion channel indirectly, via a lipid-mediated mechanism. Confirmation of this hypothesis would demonstrate an entirely novel mechanism of protein-protein interaction. NMR structural studies of the toxins in the membrane, as well as solid-state NMR studies of the membrane itself, could offer insight to the molecular mechanism of this ion channel inhibition.
The development of antibiotic resistant microbes has driven a huge search for new antibiotics, and antimicrobial peptides are one of the main targets of investigation. The peptides are known to compromise the integrity of the lipid bilayer of the cell they are attacking, but the mechanism is not well understood and is thought to vary from peptide to peptide. NMR allows the ability to distinguish among the different mechanisms of membrane disruption, simply by looking at the orientation of the protein on the membrane surface. Of particular interest is a group of antimicrobial hexapeptides that demonstrates specific activity against a class of fungi but shows no effect on E. Coli or S. Cerevisiae. Such specificity is unusual in antimicrobial peptides, possibly indicating a unique mechanism of action, and is of great interest in antibiotic development.
1 Lee, S.Y. and R. MacKinnon, A membrane-access mechanism of ion channel inhibition by voltage sensor toxins from spider venom. Nature, 2004. 430(6996): p. 232-235.
Awards
NSF Mathematical and Physical Sciences Distinguished Research Fellow: 2003-2005; NSF Predoctoral Fellowship: 1998 - 2001
Selected Publications
"Development of a functionalized xenon biosensor," Spence M.M., Ruiz E.J., Rubin S.M., Lowery T.J., Winssinger N., Schultz P.G., Wemmer D.E., Pines A., J. Am. Chem. Soc., 2004, 126 (46), 15287-15294.
"Remote detection of laser-polarized xenon," Moule A.J., Spence M.M., Seeley J.A., Pierce K.L., Saxena S.K., Pines A., Proc. Nat. Acad. Sci., 2003, 100 (16), 9122-9127.
"Functionalized xenon as a biosensor," Spence M.M., Rubin S.M., Dimitrov I.E., Ruiz E.J., Wemmer D.E., Pines A., Yao S.Q., Feng T., Schultz P.G., Proc. Nat. Acad. Sci., 2001, 98 (19), 10654-10657.