Michael J. Bruno
Post-Doctoral Fellow
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Position:

PhD. Candidate in Biochemistry and Structural Biology, Weill Medical College of Cornell University, New York, NY

Synopsis of Current Resarch:

At low micromolar concentrations, poly-unsaturated fatty acids (PUFAs) alter the function of many membrane proteins - including ion channels. PUFAs may act by binding to membrane proteins, but they exert their effects on unrelated proteins at similar concentrations, suggesting a common mode of action that does not involve specific binding. Because the membrane's lipid bilayer serves as the common "solvent" for all membrane proteins, it is reasonable to consider the possibility that PUFAs alter membrane protein function by a bilayer-dependent mechanism. Indeed PUFAs modify bilayer properties, promote a negative lipid curvature and, being reversibly adsorbing amphiphiles, would be expected to alter the bilayer elastic moduli. Thus, PUFAs could alter bilayer material properties by adsorbing at the bilayer/solution interface and in turn alter protein function. Negative changes in curvature would be expected to decrease gramicidin channel appearance rate and lifetimes; increases in bilayer elasticity would have the opposite effect. In my research I use gramicidin analogues of different sequence length and bilayers of different thickness to assess whether PUFAs may exert their effects through an indirect (bilayer-mediated) mechanism. I quantified the changes in channel properties for increasing concentrations (3 - 30 µM) of n-3 and n-6 fatty acids. In most cases, PUFAs decrease bilayer stiffness and thereby increase channel lifetime and appearance rate, suggesting that the changes in elasticity dominate over changes in curvature. The changes in channel lifetimes increase with increasing channel-bilayer hydrophobic mismatch imposed by changes in channel length at a constant bilayer thickness or changes in bilayer thickness at a constant channel length. Under certain conditions (i.e. with low hydrophobic mismatch or thick membranes), the negative changes in curvature induced by PUFAs overcome the increase in bilayer elasticity to decrease the channel lifetime. Thus, I have been able to show that the general ability of amphipathic compounds to alter membrane protein function by decreasing the bilayer stiffness is governed by the interplay between its ability to alter the lipid or monolayer curvature and its ability to soften the bilayer by increasing bilayer elasticity. This dynamic provides a framework for understanding the role of the bilayer in the regulation of integral membrane protein function.

Education/Training:

Institution and Location Degree Year(s) Field of Study
Dartmouth College, Hanover, NH B.A. 1999 Physical Biochemistry
Weill Medical College of Cornell University, New York, NY PhD. Candidate Present Biochemistry and Structural Biology

Work:

2004-2005 Co-Chair, Problem-Based Learning Workshops
2000-Present Presenter, Cornell Institute for Biology Teachers
2001-Present Co-Chair, Cornell Science Challenge

Honors:

1999 Honors in Chemistry, Dartmouth College
2004-2005 Jacques Cohenca Predoctoral Fellowship, Cornell University

Publications: