Prof. Michelle Knowles and her group are interested in understanding how membrane proteins function on a molecular level. They use single molecule and quantitative imaging techniques to form spatio-temporal maps of fluorescently labeled proteins and develop methods for measuring transient protein-protein interactions in live cells and biochemical systems. Her lab currently focuses on two different proteins systems: SNARE proteins and P-glycoprotein. The SNARE proteins provide the energy needed for membrane fusion and are essential to neurotransmission, membrane repair, and intracellular membrane transport. VAMP, a SNARE protein located on a vesicle, and the plasma membrane SNAREs, Syntaxin and SNAP25, come together to form a ternary protein complex. When the cell secretes the vesicle contents, the three SNAREs interact and fold to form a very stable ternary complex that is thought to cause the membrane of the vesicle to merge with the plasma membrane. P-glycoprotein (P-gp) is a large membrane protein that removes toxic chemicals from the cell by hydrolyzing ATP. The upregulation of P-gp has been correlated to multidrug resistance in cancer and had been show to decrease survival rates. P-gp removes chemotherapeutic drugs and renders the cell resistant to treatment. We are developing methods to address how P-gp functions on a molecular level and how efflux is activated and halted with drugs. Ultimately, armed with a molecular understanding of P-gp, drugs that are capable of eluding or overcoming this drug resistance mechanism can be developed. To study these proteins, the Knowles' lab uses total internal reflection fluorescence microscopy, an imaging technique that preferentially illuminates the surface of the cell. In doing so, the background is greatly reduced and allows for single molecule imaging. Single molecules have been used as a calibration for measuring the number of proteins in a complex and are also used to study the dynamics of proteins. Single molecule techniques are ideal for characterizing how a protein works and have been used to reveal molecular mechanisms of protein function. Spatio-temporal mapping allows us to connect protein function with clustering, mobility and location. Technique and algorithm development plays a key role in this research as the Knowles' group aims to identify transient protein-protein interactions from imaging data.
The Pegan laboratory's research goal is to gain a greater understanding of the mammalian innate immune response and how it is modulated, as well as develop new therapeutic templates for emerging diseases. Our on-going intent is to investigate the anti-viral type I response through the structural and kinetic study of proteases and ligases involved in the immune response signaling pathway. Through this research a better understanding of the role these proteins play in cellular regulation of the innate anti-viral immune response will occur. This insight will allow us to pioneer treatments for viral infection as well as autoimmune and cancer disorders. In addition, we also intend to seek new antibiotic templates for Tuberculosis using structure based drug design and high-throughput screening. Click on the picture below to see a video of their research.