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Thomas McIntosh, Cell Biology

Our laboratory is interested in the structure and function of biological membranes. We currently have two primary areas of focus: (1) the properties of membrane microdomains or „rafts‰ and (2) the cell lytic effects of antimicrobial peptides.

In the first area of interest, we are using a variety of biophysical techniques to analyze the structure of membrane rafts, the mechanisms by which rafts form, and the interactions of raft and non-raft bilayers with peptides of biological interest. Rafts, which have been isolated from both biological membranes and bilayers containing specific classes of lipids, sequester specific membrane proteins and are thought to play important roles in cellular processes such as endocytosis, protein and lipid trafficking, and signal transduction. We have found that the thickness and mechanical properties of rafts are different than typical membranes, and these differences have profound effects on their interactions with peptides and proteins.

In the second area of focus, we are determining the roles of membrane components in governing how specific antimicrobial peptides lyse cells. Appreciation is rapidly growing for the part of the innate defense system that depends on these peptides to kill a wide range of microbial invaders. Most of these peptides do not act primarily on specific processes or proteins in the invading microbe, but begin killing the microbe by disrupting the barrier function of the cell membrane. Specifically, their main target is the lipid bilayer of the microbe's membrane. Because these peptides work on basic physical properties of the membrane bilayer to initiate cell death, microbes have difficulty in developing resistance to these peptides. One specific question we are addressing is the reason host eukaryotic cells are much less sensitive to these peptides than are bacterial cells.

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