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Antimicrobial
Peptides
Antibiotics have changed the course of human history saving innumerable lives and substantially improving the quality of life across the globe. Bacteria are fighting back though. Superbugs, species that do not respond to our most potent drugs, are evolving, infecting humans with alarming frequency. And our drug war chest is not being updated with new antibiotics because of this oxymoronic financial disincentive: one dose, one treatment with antibiotics may cure the disease, in stark contrast to medicines prescribed for life.
In our group, we borrow from nature and harness the potential of antimicrobial peptides (AMPs). These are small proteins most all higher organisms produce that lyse and kill bacteria rapidly. AMPs have been successful during evolutionary timescales, so there is only slight chance bacteria could quickly develop resistance to them. A major hurdle in using these very potent molecules in our fight against bacteria is that at sufficiently large concentrations they may lyse host red blood cells.
We use mathematical models, to explain the ways these molecules disrupt bacterial and human cells. With detailed explanations we should have a better chance of designing antimicrobial peptides with therapeutic potential. Typically, as is well established, antimicrobial peptides bind on cell membranes, form aggregates, and disrupt the integrity of the membrane. What is not known is the set of thermodynamic and kinetic driving forces behind all the biophysical steps that underlie biological function, and what are the sequence and structural features of AMPs that render them bactericidal and toxic.
With collaborators at the Centers for Disease Control and the Medical School at UCLA we are engineering new AMPs with therapeutic potential.
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