A biochemist at the University of Massachusetts has received a four-year $308,000 grant from the American Heart Association.

The grant was awarded to Alejandro P. Heuck in order to further the development of molecular probes that are able to measure cholesterol levels in the membranes of single cells.

The probes are determined to be useful in evaluating the effect of new cholesterol-lowering drugs. There is also the potential that the probes could be used as a diagnostic tool for people with both Alzheimer’s disease and atherosclerosis, hardening of the arteries.

According to Heuck, atherosclerosis is the major disease associated with cholesterol and lipid metabolism, and atherosclerosis vascular disease has the possibility of becoming a worldwide leading cause of death by 2020.

“Development of these molecular probes will allow us and others to precisely assess cholesterol levels in cell membranes and to study its regulation when cells are subjected to different stimuli or drug treatments,” said Heuck.

One question Heuck plans to address with this grant is how a natural cholesterol-binding protein can be modified to develop these probes that measure the cholesterol levels in cellular membranes.

He said there is a certain type of protein from the pathogenic bacteria Clostridium perfringens that has evolved to specifically recognize cholesterol in eukaryotic membranes. Since this protein only attaches to membranes with high cholesterol levels, Heuck plans to take advantage of the properties of the protein in order to design these probes that recognize cholesterol on cellular membranes.

“In particular, we are looking for mutant proteins that recognize only low or high levels,” said Heuck.

In addition, he will generate probes that selectively attach to cells with a specific level of cholesterol and then label each probe with a different color fluorescent dye. In this case, the probes will be used to study cholesterol regulation in cell membranes of macrophages, which are immune system cells that affect the formation of the arterial deposits within atherosclerosis. Heuck hopes that his work will allow other biochemists to “precisely assess cholesterol levels in the cell membranes, and to study its regulation when the cells are subjected to different stimuli or drug treatments.” “Initially, we will apply these novel probes to analyze cholesterol homeostasis in macrophages, given their key role on atherosclerosis,” he said.

The American Heart Association Scientist Development Grant, which began Jan. 1, is awarded to highly promising beginning scientists. The program hopes to encourage and fund research projects in order to create a link between the completion of research training and competition as an independent researcher.

“The goal of this project is to develop unique molecular probes that will ultimately allow the quantification and imaging of distinct cholesterol levels in cell membranes,” Heuck said.

Kristen Healy can be reached at [email protected].