Array of light for early disease detection?

A special feature in the May 11 issue of the journal Science highlights protein array technology, touching on research conducted by Joshua LaBaer, director of the Biodesign Institute’s Virginia G. Piper Center for Personalized Diagnostics.

With the successful completion of the Human Genome Project, research attention is increasingly focusing on proteins. Versatile products produced from genetic templates, proteins are principle actors in both the maintenance of health and the onset of illness. Protein microarrays are a means of bridging the gap between analysis of the nucleotide sequences that make up DNA and the proteome - the universe of proteins built from the amino acids coded for by genes.

Protein microarrays are helping researchers develop early detection methods, particularly for chronic diseases, which account for most of the country’s health care expenditures. Identifying telltale signs of diabetes, coronary artery disease, congestive heart failure and various cancers at an early, pre-symptomatic stage, offers the best prognosis for successful treatment, at dramatically reduced cost.

"Proteins are the machines of biology. Disease is nearly always a result of protein malfunction, and most drugs are designed to affect protein function. Protein microarrays enable us to test the biochemical properties of thousands of proteins simultaneously," says LaBaer.

While the genome provides the instruction manual for building living systems, proteins are the real molecular workhorses, faithfully carrying out genomic instructions, while also modifying their behavior under myriad environmental influences. Proteins provide structure to cells and tissues, facilitate signaling within and between cells, act as receptors, catalyze enzymatic activity, execute immune functions, and perform countless other biological tasks.

A more thorough understanding of the proteome is therefore vital to diagnostic medicine, particularly for establishing biomarkers—pre-symptomatic indices of early disease states, detectable as protein components in blood. LaBaer's group is working on discovering biomarkers for a range of deadly illnesses, including, breast, ovarian, lung and oropharyngeal cancers; type I diabetes and assorted infectious pathogens.

Until recently, studying the complexities of proteins, (as opposed to the sequence of four nucleotides making up DNA), has been daunting. A protein microarray usually consists of a library of proteins immobilized on a glass slide or chip in a 2D addressable grid format. Arrays of this sort are made by expressing and painstakingly purifying proteins, then imprinting them onto the slide's surface. Once a library of proteins has been splayed out on an array, high-throughput methods can be used to investigate their behavior.

Similar arrays have long been used to study DNA, yielding a steady stream of insights into the genome and in some cases providing rapid and accurate diagnostic tools. Researchers would like to repeat the successes of DNA microarrays with protein microarray technology, though a number of hurdles exist. Compared with nucleic acids, proteins exhibit enormous structural diversity and complexity. The synthesis, stabilization and purification of proteins are often laborious undertakings. Adequately attaching proteins to the array surface is tricky and subsequent detection of these proteins through binding events is considerably more complex than in the case of nucleic acid arrays.