AGGREGATION ASSAY: To detect clumping of a protein of interest, express it together with a synthetic transcriptional activator domain (grey). If the protein remains soluble, the reporter gene (green), which is under the control of a synthetic promoter that corresponds to the activator, will be expressed. If the proteins clump together, it will not. © GEORGE RETSECK
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The aggregation of cellular proteins into insoluble clumps is a hallmark of many diseases, including Alzheimer’s, Parkinson’s, systemic amyloidosis, prion diseases, and type 2 diabetes. Protein agglomeration can also be a feature of normal cellular functions, such as signal transduction, synapse modification, and the regulation of RNAs during cellular stress.
Tools for studying such physiological and pathological protein aggregations, however, are limited, explains biomedical engineer Ahmad Khalil of Boston University. The principal options for researchers, he says, are either to destroy cells and analyze their innards for protein aggregates, or append a fluorescent tag to the proteins of interest within cells and view the formation of clumps (bright spots) with a microscope.
While this second option maintains the protein’s normal physiological surroundings, Khalil says, “inherently ...
