Sterol transport and cell-cycle requirements for isoprenoids

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Cholesterol is a necessary evil. Too much cholesterol leads to disease, but some cholesterol is nonetheless needed for normal cell growth. Cholesterol and related lipids are required for the structure of the membrane that envelopes cells, and cholesterol affects the function of proteins embedded within this membrane. In addition to the transport mechanisms that move cholesterol through our bodies, cholesterol must also be transported within the cell interior. The mechanism for how cholesterol moves within cells is poorly understood. OSBP-related proteins (ORPs) are implicated in the transport of cholesterol within cells, but how these proteins might accomplish that function is controversial. We have chosen to study ORPs and the transport of cholesterol-related sterols in yeast cells, which can be easily exploited using a large variety of molecular genetic techniques. Yeast also represent simple versions of our own cells, so what we learn in yeast can be applied to studies of cholesterol transport in human cells. The goal of our work is to define how cholesterol is transported within cells, and to understand how cholesterol and its biosynthetic precursors affect cell growth and division.