Spring 2015 Courses
Biomolecular NMR - Structure and Molecular Recognition
Nuclear magnetic resonance spectroscopy (NMR) is a powerful tool for the interrogation of biomolecular structure and interactions at atomic resolution. Structural genomics efforts have produced refinements in the methodology for three-dimensional protein structure determination, such that new structures can be solved in a matter of weeks using increasingly automated processes. This course begins with a description of the quantum mechanical basis for multidimensional NMR using the product operator formalism. This powerful operator algebra rigorously predicts the propagation of the nuclear spin wavefunction under a time-independent Hamiltonian operator governing interactions between nuclear spins and between spins and static or transient magnetic fields, enabling the development of increasingly complex pulse sequences for multidimensional, multinuclear NMR measurements of biomolecules. Simple pulse sequences for magnetization transfer and isotope editing are described using product operators and combined into more complex two- and three-dimensional pulse schemes for triple-resonance correlation of nuclei in proteins. Systematic application of these NMR methods to the sequence-specific assignment of isotopically enriched proteins will then be linked to the interpretation of other of types NMR data (nuclear Overhauser effect; scalar and dipolar couplings) that report directly on tertiary structure. The balance of the course will consist of practical, hands-on training in basics of 2D/3D NMR data acquisition, processing and analysis, as well as interactive computer tutorials on the chemical shift assignment and 3D structure determination processes.
Contemporary X-ray Crystallography
X-ray crystallography is the main method for elucidating 3-dimensional structures of macromolecules and biomolecular complexes. This method is capable of revealing structural details at high resolutions (finer than 3.5 Å). Powered by modern synchrotron-based light sources and state-of-the-art computer programs, contemporary crystallographic research has provided mechanistic insights into complex cellular functions such as gene transcription and translation. While crystallographic computer programs are openly available, the use of these packages by biologists who do not have a theoretical comprehension of crystallography can be unproductive. This course is designed to teach non-crystallographers the capability to intelligently use crystallographic programs that are often available in the form of bundled software. Attendees will learn systematically the central theory behind the crystallographic tools in use today, and hence grow an appreciation of the physical process that takes place during an experiment to determine the structure of a protein or nucleic acid. A central aim of this course is to generate stimulating discussions that will help the students to grasp the essence of macromolecular crystallography.
Special Topics in Biochemistry - Oxidative Stress Signaling in Cancer
This course will focus on the role of oxidant-activated signaling cascades in neoplastic transformation. Major areas to be covered include: (a) reactive oxygen and reactive nitrogen species (ROS, RNS) as second messengers; (b) metabolic vs. non-metabolic ROS/RNS sources; (c) cellular targets of oxidative attack; (d) preventative and reparative antioxidant defenses; (e) activation and regulation of redox signaling cascades; (f) proliferative vs. apoptotic signaling under oxidative pressure; (g) dysregulated redox metabolism in cancer and (h) signaling events in oxidant-based tumor therapies. Students are expected to develop an advanced understanding of various aspects of oxidative stress signaling in tumorigenesis through introductory lectures, outside readings, and in-class discussions.