In 1993, their postdoctoral trainees, Wang Xiaodong and Michael Briggs, purified the Sterol Regulatory Element-Binding Proteins (SREBPs), a family of membrane-bound transcription factors. Since 1993, Goldstein, Brown, and their colleagues have described the unexpectedly complex machinery that proteolytically releases the SREBPs from membranes, thus allowing their migration to the nucleus where they activate all the genes involved in the synthesis of cholesterol and fatty acids. The machinery for generating active SREBPs is tightly regulated by a negative feedback mechanism, which explains how cells maintain the necessary levels of fats and cholesterol in the face of varying environmental circumstances.