James Clack
associate professor of biology
IUPU Columbus

"The eyes are the windows to the soul," as the saying goes.

James Clack, associate professor of biology at Indiana University Purdue University Columbus, and his colleagues are trying to pull back the curtains on the fascinating visual structure of the eye and find out what's going on inside.

The ability of rods and cones in the eye (photoreceptors) to respond electrically to light (photoresponse) and relay that response to the brain underlies our ability to see. The generation of this photoresponse is controlled by a number of enzymes and chemicals, together called the "light-activated cyclic nucleotide cascade."

The protein Transducin performs a key role in this cascade by linking the absorption of light with changes in the electrical activity of the photoreceptors. Clack studies the structural and functional subunit interactions of Transducin.

Transducin is composed of three different subunits, alpha, beta, and gamma. Clack and his colleagues have recently shown that in the normal eye, the three subunits are present in different amounts, with the beta and gamma subunits being roughly three times as abundant as the alpha subunit. They believe that this difference in abundance may affect the sensitivity, latency, or duration of photoresponses to a light stimulus.

The group is also investigating the structural and functional differences in the different subunits that make up Transducin. For example, they have determined that there are as many as eight isoforms of the beta subunit of Transducin present in normal photoreceptors. These isoforms have very different physical and chemical properties and may be involved in altering the photoreceptors' response to light. Alternatively, the subunit alterations may control whether or not a particular subunit functions at all.

Along with Frank Witzmann, professor of cellular and integrative physiology of the IU School of Medicine, Clack is continuing to probe the molecular basis of these alterations by using classic biochemical techniques combined with an emerging method of inquiry called proteomics.

"It is critical for us to understand in as much detail as we can how the eye performs its magical conversion of light stimuli into information and perception in normal eyes, so that we can better understand the nature of some types of blinding eye disease," Clack says. "Study of the light-activated cyclic nucleotide cascade will also give us insights into the working of closely related signal transduction systems such as those that control heart function and many other systems where a stimulus evokes a response in a target organ or tissue."

Clack hopes that his research will "shed some light" on how we see and what goes wrong when we cannot.