Grant: Discovery Grants Program - Individual

) Enzymes are molecules that allow reactions to occur at the appropriate rate in a cell under physiological conditions. The health of a cell is totally dependent upon such reactions. However, since the requirements of a cell change with differing conditions, so must the rates of many of the reactions sustaining the cell. Since it is enzymes that control these rates, it is essential for a cell to be able to regulate these enzymes to ensure that all of a cell's requirements are being properly met. ) Since molecules are so small, chemical studies have classically involved measurements made on a very large number of seemingly identical molecules. All the data obtained reflects average values for the characteristics being measured. If differences between individual molecules existed, they would not be detected due to the very large scale averaging. ) Over the past years, scientists have developed methods to measure the characteristics of individual molecules, including enzymes. With enzymes an interesting finding was made: Individual molecules of a given enzyme do not have identical properties. This means that in order to regulate its chemistry, a cell must alter the distribution of characteristics of an enzyme population. The means by which this is achieved is not understood. ) In my research we use the enzyme beta-galactosidase as a model to study the structural differences which underlie enzyme microheterogeneity and how a cell can alter the distribution of properties of a population of individual enzyme molecules in order to regulate its chemistry. This is done with the use of single enzyme molecule measurements. The effect of a given treatment on the distribution properties of the composite individual molecules of an enzyme population is measured. This is performed to provide insight into the structural differences between the individual molecules and to determine how the cell can alter the distribution of properties to effect a desired change in the overall population characteristics. This will increase our overall understanding of how cell chemistry is controlled and how this relates to the states of both health and disease. )