2019-20 Catalog: Biochemistry & Molecular Biophysics

Learn about viruses as fascinating biological machines, focusing on naturally-occurring and evolved variants, in silico viral vector engineering, and computational methods that include structure visualization and machine learning. This course will introduce the fundamentals in the chemistry and biology of viruses, emphasizing their engineerable properties for use in basic research and translational applications. Topics include: viruses by the numbers, mammalian and non-mammalian (plant, bacteria) viruses, enveloped vs. non-enveloped viruses, host-virus interactions, viral life cycles (replication vs. dormancy), immune responses to viruses, zoonosis, diverse mechanisms of entry and replication, the application of viruses as gene-delivery vehicles (with a focus on adeno-associated viruses or AAVs, lentiviruses, and rabies), and how to engineer viral properties for applications in basic research and gene therapy. The lectures will be complemented by short lab exercises in AAV preparation, bioinformatics and machine learning, and structure visualization. Given in alternate years; offered 2019-20.

Basic principles of modern biophysical and structural methods used to interrogate macromolecules from the atomic to cellular levels, including light and electron microscopy, X-ray crystallography, NMR spectroscopy, single molecule techniques, circular dichroism, surface plasmon resonance, mass spectrometry, and molecular dynamics and systems biological simulations.

Discussion of research fields in biochemistry and molecular biophysics at Caltech.

Discussion of the energetic principles and molecular mechanisms that underlie enzyme's catalytic proficiency and exquisite specificity. Principles of allosteric regulation, selectivity, and enzyme evolution. Practical kinetics sections discuss how to infer molecular mechanisms from rate/equilibrium measurements and their application to more complex biological systems, including steady-state and pre-steadystate kinetics, kinetic simulations, and kinetics at the single molecule resolution.

A course that includes a seminar on selected topics from outside faculty on recent advances in biochemistry. Students will participate in the seminar along with a formal discussion section with visiting faculty. Students will meet with the Biochemistry seminar speaker in the discussion section for an hour, and then attend the Biochemistry seminar at 4 p.m. BMB Seminars take place 1-2 times per month (usually on Thursdays).

Advanced course in macromolecular crystallography integrating lecture and laboratory treatment of diffraction theory, crystallization (proteins, nucleic acids and macromolecular complexes), crystal characterization, X-ray sources and optics, crystal freezing, X-ray diffraction data collection (in-house and synchrotron), data reduction, multiple isomorphous replacement, single- and multi-wavelength anomalous diffraction phasing techniques, molecular replacement, electron density interpretation, structure refinement, structure validation, coordinate deposition and structure presentation. In the laboratory component, one or more proteins will be crystallized and the structure(s) determined by several methods, in parallel with lectures on the theory and discussions of the techniques

Presentations and discussion of research at Caltech in biology and chemistry. Discussions of responsible conduct of research are included.

Students may register for research units after consultation with their adviser.