The major scientific contributions of the Sigler laboratory concerned three areas. His studies showed how small molecules, such as steroid hormones, can bind to a protein and alter its structure, thereby altering the protein's affinity for DNA signals at the beginning of a gene and the expression of the information in that gene. These studies have implications for understanding cell development, cancer and hormone regulation. The second area of major scientific contribution by the Sigler lab involves the signal transduction pathway involved in vision. The enzymatic chemical steps that are initiated by light falling on the retina and ending in a signal to the brain are being unraveled at a molecular level, including the mechanism whereby a central protein called a G-protein is regulated as a part of the signaling cascade.
Related proteins form an important family of oncogenes.
Perhaps among his most stunning technical achievements was the structure determination of a large assembly of protein whose function was to form a machine that assures the correct folding of other newly synthesized proteins into their correct three-dimensional structure. This macromolecular machine is among the largest structures solved and provided unprecedented mechanistic insights into a catalyzed process whose existence was not even known until relatively recently. Sigler's impact on the field of structural biology far exceeded his own contributions, as enormous as they are. Beyond his science, he was an exciting and enormous presence, an engaging teller of many stories and a person who befriended and communicated his enthusiasm for science to many all over the world. Sigler is survived by his wife, Jo, their five children, and a brother, Miles.