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Programmable BioMolecular Circuits: Emulating Regulatory Functions in Living Cells Using a Bottom-Up Approach

Periodic Reporting for period 2 - BioCircuit (Programmable BioMolecular Circuits: Emulating Regulatory Functions in Living Cells Using a Bottom-Up Approach)

Reporting period: 2018-02-01 to 2019-07-31

Living cells form the basis of life. Cells have evolved to process an enormous amount of chemical signals using dedicated molecular networks. However, because of the high complexity of the living cell, unraveling the design principles of these molecular networks has proven impossible. In this project, we have build molecular networks outside of the living cell with the objective of studying the design principles of molecular networks using a bottom-up approach. Such an approach can provide detailed answers on the way molecular networks are able to process information. This is important for society as malfunctioning of molecular networks in living cells can lead to diseases such as cancer. Therefore understanding how molecular networks achieve their function and how they fail is an important research question that is important for society.
In the first period, we designed several genetic circuits and tested the response of these circuits in silico. We have designed and tested the microfluidic devices that will be used to test run genetic programs outside of the living cell. In addition, we have cloned DNA constructs and tested them in cell lysate. In the next period, we will prototype the cell-free genetic circuits in our microfluidic flow reactors.
Understanding the design principles of genetic circuits is currently extremely difficult due to the extreme complexity of the living cell. Our project will uncover basic principles of genetic circuits by reconstituting them outside the cell by combining cell-free protein synthesis and microfluidic flow reactors. Understanding the design principles of genetic circuits will allow us to better understand the origin of complex diseases like cancer.