Anna Liachenko, BSc, MSc
Managing Editor,
Geriatrics & Aging
In a stunning presentation at the National Academy of Engineering meeting, Thomas J. Meade of the California Institute of Technology presented frog embryos unfolding from egg to tadpole stages. The images provided an unprecedented degree of cellular resolution, allowing one to see a cell reacting to alterations in a single gene. The technique perfected by Meade and his colleagues represents a major advance in functional nuclear magnetic resonance (NMR) technology.
Positron Emission Tomography (PET) and functional magnetic resonance imaging (fMRI) are both known to reveal sites in the living brain or other tissues that are active when a person is engaged in performing a particular task. These techniques have provided an extraordinary amount of biological information and are among the most important advances in medical science.
The Meade technique uses a novel contrast agent that identifies specific cells when their genes are turned on. NMR relies on the detection of vibrations in hydrogen atoms of water that are induced by a magnetic field. Contrast agents, such as gadolinium, are often added to enhance hydrogen's signal emission. This technique provides a powerful means to image the topography of soft tissue, but cannot provide a deeper level of resolution.
Meade has discovered an elegant and economical solution to one of the most significant problems in biological science: how to provide functional images of cellular level activity. He solved this problem by constructing a 'molecular basket' for each gadolinium ion. The basket consists of claw-like molecules called chelators. He then created a lid for the basket made out of galactopyranose. The 'closed basket' was injected into both cells of a two-cell frog embryo. One of the two cells was also injected with the gene for galactopyranose-digesting enzyme. Upon synthesis of the galactopyranose-digesting enzyme, the galactopyranose 'lid' was digested, exposing gadolinium to water, resulting in a bright signal. The principle of this technique can potentially be used for detecting any enzyme. Thus, one can create a general method for tracking the changes in any cell, or cellular pathway. Even more exciting is research aimed at finding a way of attaching a drug to the 'basket' and activating it with a particular enzyme within a cell. The potential for this new delivery system is enormous.
Advances in aging research will require understanding the activities and interactions of hundreds of genes. The ability to resolve functional NMR images down to the cellular level will have enormous implications for this research.
