B.A.Sc. (Toronto), Ph.D. (Minnesota), P.Eng.
Principal Investigator, Yip Research Lab
Fellow, Engineering Institute of Canada, 2013
Fellow, American Association for the Advancement of Science, 2009
Graduate Faculty Teaching Award for Sustained Contribution to Excellence in Teaching, University of Toronto Faculty of Medicine, 2008
Tier 2 Canada Research Chair, 2000-2010
Faculty Teaching Award, 2000/01
Premier’s Research Excellence Award, 1999
Molecular Imaging Corp. Young Biological Scanning Probe Microscopist of the Year, 1998
Microscopical Soc. of Canada – Ont. Section Chair
Professional Engineers of Ontario
American Chemical Society
Chemical Institute of Canada
Canadian Society for Chemical Engineering
Molecular Engineering and Single Molecule Biophysics
Molecular engineering refers to the molecular level control of materials through rational control of chemical structure, molecular conformation, and solid-state packing. The study of molecular engineering draws influences from fields as diverse as organic chemistry, biochemistry, structural biology, and chemical engineering. Indeed control over processes ranging from the crystallization of biomolecules and pharmaceuticals to the formation of protein complexes requires an in-depth understanding of the subtle structural and chemical factors controlling the processes of molecular self-assembly and recognition.
Our research efforts are directed at the in situ characterization of molecular self-assembly, which has clear implications for understanding processes ranging from the crystallization of biomolecules and pharmaceuticals to the interaction of protein and drug molecules with cellular membranes. Through a combination of in situ scanning probe microscopy (SPM) with other techniques including circular dichroism, light scattering, X-ray scattering, NMR spectroscopy, and infrared and Raman spectroscopy, we are endeavouring to develop models for these processes. Collaborations with structural biology and crystallography research groups at the University of Toronto in additional to external programs with pharmaceutical companies offer an excellent opportunity to study a variety of biomolecular phenomena and processes of therapeutic interest.
The design of novel molecules and proteins for therapeutic applications requires an understanding of how these molecules interface with their complementary sites in the body. Thus it becomes clearly important to characterize the structure of these binding sites and X-ray crystallography remains one of the main means for acquiring high-resolution structural data. However, traditional diffraction techniques cannot readily provide information about the kinetics of crystal growth or local disorder.Thus we are using in situ SPM to assess the structure of protein crystals at the crystal-solution interface. These studies will provide information on the kinetics of crystal growth and, perhaps more importantly, the role of defects on crystal dissolution, which is of key importance for the bioavailability of crystalline pharmaceuticals. We are also investigating the formation of protein complexes on model lipid bilayers. This approach has shown promise for understanding the mechanisms associated with protein complexation on cell membranes, including the action of viral proteins. Similarly, we are also studying the process of protein aggregation and fibril formation at model interfaces, which has significant implications for the design of novel biomimetic materials. The ability to achieve near-molecular scale resolution in the absence of staining and high vacuum techniques suggests an ideal opportunity to characterize the factors that influence these processes under native conditions.
The high force sensitivity of the scanning probe microscope has enabled researchers to directly measure intermolecular forces, including ligand-receptor interactions, using chemically modified SPM tips and surface immobilized molecules. This approach affords a unique opportunity to directly probe an envelope of association energies, which complements traditional equilibrium association measurements and has clear application to the characterization of other systems including force mapping of biological membrane surfaces and the interaction between novel ligands and specific binding sites which may have importance for the screening of new drug molecules.
Furthermore, our group is actively involved in the design, fabrication, and application of novel molecular scale functional imaging tools as well as computational approaches to understanding molecular structure, function, and assembly.
Indolicidin Binding Induces Thinning of a Lipid Bilayer Neale, C., Hsu, J.C.Y., Yip, C.M., Pomes, R. Biophysical J. 2014 Apr 15;106(8):L29-31
The Mechanism Of Membrane Disruption By Cytotoxic Amyloid Oligomers Formed By PrP(106-126) Is Dependent On Bilayer Composition Walsh P., Vanderlee, G., Yau, J., Campeau, J., Sim, V.L., Yip, C.M., Sharpe, S. J. Biol. Chem. 2014 Apr 11;289(15):10419-10430
Inside-Out Signaling Promotes Dynamic Changes In The CEACAM1 Oligomeric State To Control Its Cell Adhesion Properties Patel, P, Lee, H.S., Ming, A., Rath, A., Deber, C., Yip, C.M., Rocheleau, J.V, Gray-Owen, S.D. Journal of Biological Chemistry: 2013 Oct 11;288(41):29654-29669
The Sticholysin Family Of Pore-Forming Toxins Induce The Mixing Of Lipids In Membrane Domains Ros, U., Edwards, M.A., Epand, R.F., Lanio, M.E., Scherier, S., Yip, C.M. Alvarez, C., Epand, R.M. BBA – Biomembranes 2013 Nov;1828(11):2757-2762.
Forces Of Interactions Between Bare And Polymer Coated Iron And Silica: Effect Of pH, Ionic Strength And Humic Acids Pensini, E, Sleep B, Yip, C.M., O’Carroll, D., Environmental Science and Technology, 2012, 46(24):13401-13408
Charge Carrier Mobility In Fluorinated Phenoxy Boron Subphthalocyanines: The Role Of Solid State PackingCastrucci, J., Helander, M,, Morse, G., Lu, Z-H, Yip, C.M., Bender, T. Crystal Growth and Design, 2012, 12(3). 1095-1100
Roles of Hydrophobicity and Charge Distribution of Cationic Antimicrobial Peptides in Peptide-Membrane Interactions Yin, L.M., Edwards, M.A., Li, J., Yip, C.M., Deber, C.M. J. Biol. Chem 2012, 287, 7738-7745
Dynamic Macrophage “Probing” Is Required For The Efficient Capture Of Phagocytic Targets Flannagan, R.S.; Harrison, R.E; Yip, C.M.; Jaqaman, K.; Grinstein, S. J. Cell. Bio. 2010 Dec 13;191(6):1205-1218
Peptide-Induced Domain Formation In Supported Lipid Bilayers: Direct Evidence By Combined Atomic Force And Polarized Total Internal Reflection Fluorescence Microscopy Oreopoulos, J.; Epand, R.Q.; Epand, R.M; Yip, C.M. Biophys J. 2010 Mar 3;98(5):815-823. (80% effort)
Supported Lipid Bilayer Templated J-Aggregate Growth: Role of Stabilizing Cation-π Interactions and Headgroup Packing Mo, G.; Yip, C.M. Langmuir 2009 Sep 15;25(18):10719-10729 (100% effort)
Tracking Molecular Interactions in Membranes By Simultaneous ATR-Fourier-Transform Infrared Spectroscopy-Atomic Force Microscopy. Verity, J., Chhabra, N., Sinnathamby, K., Yip, C.M. Biophys J. 2009 Aug 19;97(4):1225-1231 (100% effort).