Ronald Kaback became interested in membrane transport at a time when studies on biological membranes were in their infancy, and in the early phase of his career, he developed a
cell-free membrane system to study
active transport. The system consisted of osmotically sealed membrane
vesicles of defined orientation (right-side-out) that catalyze active transport essentially as well as intact cells, but lack subsequent metabolism of the solutes accumulated. These vesicles were dubbed
Kabackosomes by the Dutch scientist Wilhelmus N. Konings, Kaback's close friend and early collaborator. In addition to transforming the field of transport from phenomenology to biochemistry, this seminal development caused him to forego the practice of pediatrics for a career in basic science. The use of membrane vesicles from various sources has become a standard tool for testing models and performing hypothesis-driven research. Kaback demonstrated quantitatively that an electrochemical H+ gradient is the immediate driving force for accumulation of many different solutes.
Peter Mitchell who conceived and formulated the
Chemiosmotic Hypothesis considered these findings to be the most conclusive experimental support for the Hypothesis with respect to membrane transport. Kaback extended his interest to the molecular mechanism of membrane transport by focusing on the
lactose permease of
Escherichia coli (
LacY; aka the lactose/H+ symporter), which is now a paradigm for the
Major Facilitator Superfamily, arguably the largest group of membrane transport proteins. With the emergence of molecular biology, he and his colleagues pioneered Cysteine-Scanning Mutagenesis in combination with chemical modification, as well as a battery of site-directed biophysical/biochemical techniques to demonstrate almost incontrovertibly that LacY functions by a mechanism involving alternating access of sugar- and proton-binding sites to either side of the membrane. Until his death in 2019, Ronald Kaback gave lectures regularly at international meetings. In the last period of his career, his laboratory continued to extend studies on the evolution and mechanism of LacY and other symport proteins. == Awards and recognitions ==