Why sequential logic?

Cells respond to a myriad signals under most conditions and adjust their own internal mechanisms to survive. This adjustment depends not only on processing a combination of current environmental input signals, but also on determining the cell’s current state, which is a result of a series of past inputs. In digital circuit theory, this operating mode is known as sequential logic. Nowadays, a wide variety of tasks can be performed by synthetically engineered genetic circuits, mostly constructed using combinational logic. Contrast to sequential logic, its output is a function of the present input only. It is difficult to perform functions in a specific order, which has limited the widespread implementation of such systems. The ability of sequential logic circuits to store modest amounts of information within living systems and to act upon them would enable new approaches to the study and control of biological processes . A cell can be designed to do more complex work if it has more states. In other words, we can unfold a new dimensionality in designing synthetic life – time.

What did we do?

This year, the Peking iGEM team is attempting to develop a framework of biological sequential circuits that are programmable. The envisioned circuit is capable of both storing states in DNA and automatically running a series of instructions in a specific order. More specifically, the sequential logic that consists of a clock, flip flop and control unit in bacteria. The clock is an oscillator with a repeated signal cycle that serves as a "metronome" to trigger actions of sequential logic circuits. Flip-flop is a memory device that can remember states. Paired with a clock signal, it can realize state transition. The control unit is a functional part which can convert a signal from flip-flop into complex functions. With such a design, historical events are recorded and influence current cell behavior. This work tries to point the way toward building large computational sys-tems from modular biological parts—basic sequential computing devices in living cells—and ultimately, programming complex biological functions. Computers have thus become "alive". A unicellular organism itself cannot pack much computational power, but considered as a modular building block, its potential is impressive.