Provided herein are systems, methods and compositions for rendering cells or the expression of an effector protein sensitive to a predetermined condition. In one aspect, cells can be rendered dependent upon the presence of an environmental agent, e.g., an exogenous agent, without which the cell will default to expression of a death protein and be killed. In another aspect, cells can be rendered sensitive to the presence of a set of predetermined conditions such that cells will only grow when two or more necessary exogenous agents are supplied, and without either of which, the cells are killed. In this aspect, hybrid transcription factors provide a vast array of possible predetermined conditions.