Instruction in Quantitative Aspects underlying Biomedical Research.
Exposure to fundamental aspects of quantitation is now required within the graduate programs in the
Biomedical Sciences at Vanderbilt. Quantitation exposure is obtained in several ways. 1) The Biomath
program of course has a heavy required mathematics component required of all members. 2)The Chemical,
Physical and Mathematic Biology (CPMB) program which has grown in size by 250% in four years and is
currently in the process of applying for degree granting status has course in mathematics, physics and
Chemical biology as part of its curriculum. 3) IGP students can take courses in the mathematics of receptor
binding and also in biostatistics as a part of their elective menu, and typically10-15% go this route. 4) Finally
to make sue that all of our students get exposure to quantitation we are developing a new section of the IGP
core course on Bio-quantitation. This is required for all students to successfully complete the first year. It will
be taught as a full section and will encompass 15-20 formal lecture hours as well as an equal number of
flextime, enrichment hours involved in small group discussions. Details of al these course offerings are
presented in the Appendix.
The IGP Bio-Quantitation Course.
All segments will consist of a subject overview, coupled to assigned reading and problems.
Subsequently the problems will be reviewed and dissected in small-group discussions.
1.
Chemical Equilibria
Free energy
Pressure and temperature dependence
Phase changes
Application to biochemical reactions
Establishment of ion gradients (use of Nernst equation)
Application to biological systems
2.
Chemical Kinetics
Reaction rates
Rate laws
Enzyme kinetics
Reaction mechanisms
Temperature dependence of rate constants
Relationship between thermodynamics and kinetics
Applications to biological systems
3.
Ligand Binding to Macromolecules
Macroscopic and microscopic equilibrium constants
Experimental determination of binding isotherms
Application to biological systems
Cooperativity in ligand binding
Allostery
4.
Viscosity and Diffusion
Appreciate factors affecting movement within the cell of ions and macromolecules.
Sedimentation
5.
Electrophoresis
Forces existing in an electric field
Effect of macromolecule shape, molecular weight and charge
Effect of solid support
6.
Biostatistics
We will focus on specific results obtained from the literature, which we will then analyze
in such a way as to emphasize the statistical principles involved. The three situations
envisaged are (1) a transfection analysis in which multiples transfections into multiple
sets of tissue culture cells on different days are then analyzed by triplicate
determinations from each cell culture. (2) a hormone binding assay analysed by a
Scatchard plot with data points coming from the full range of binding, so that weighting
data points precedes regression analysis of the data. (3) a DNA array binding assay
will be analyzed in an attempt to demonstrate the estimation of significant changes and
to determine the significance of the claims made by the authors. In each case idealized
data sets will be supplied for practice in the statistical analysis, to be followed up with an
analysis of actual data sets reported in the literature.