Research

What is Life?

The What, Why, and How of our work

What is life, and how can it be programmed? We approach this question from two extreme ends of cellular complexity. In mammalian cells, we design protein circuits that operate within the dynamic networks of living systems, interfacing with endogenous pathways to sense, compute, and control cellular behavior. In synthetic cells, we build life-like behaviors from the bottom up using minimal molecular components, creating simplified systems that reveal the fundamental principles underlying biological organization. By working simultaneously in these highly complex and highly reduced contexts, we seek to uncover the rules that govern living systems across scales.

Molecular Computing with Protein Circuits

We design protein circuits that can programmably and robustly carry out computations both inside and outside of cells. Such circuits allow one to predictably control cell functions. Circuit components are proteins designed from scratch or optimized from existing ones, which enables full customization of their functionalities at the single molecule level. Key topics include:

Discover design principles that allow arbitrary molecular computations to be carried out by a set of interacting proteins
Scale protein circuits so they accommodate a large number of inputs and outputs
Interface protein circuits with biological processes to turn cells into living therapeutics

Related Publications

Multivalency enables signal processing at single protein levelWu, X., Jia, Y., Zhang, T., Xiong, Z., Ye, Z., Yu, G., Lei, Y., Mao, Z., Qu, V., Dang, B., Xu, Z., Chen, Z. (10/15/2025). J. Am. Chem. Soc..
A synthetic protein-level neural network in mammalian cellsChen, Z., Linton, J.M., Xia, S., Fan, X., Yu, D., Wang, J., Zhu, R., Elowitz, M.B. (12/13/2024). Science.
Programmable protein circuit designChen, Z., Elowitz, M.B. (4/29/2021). Cell.
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De novo design of protein logic gatesChen, Z., Kibler, R.D., Hunt, A., Busch, F., Pearl, J., Jia, M., VanAernum, Z.L., Wicky, B.I.M., Dods, G., Liao, H., Wilken, M.S., Ciarlo, C., Green, S., El-Samad, H., Stamatoyannopoulos, J., Wysocki, V.H., Jewett, M.C., Boyken, S.E., Baker, D. (4/3/2020). Science.

De Novo Design of Synthetic Cells

Living cells maintain themselves by coupling information storage, molecule regeneration, and spatial organization. We ask what is minimally required for these processes to become life-like by building synthetic cells from the bottom up. Our approach combines natural biological components with de novo designed protein modules to create synthetic cells whose replication and division can be modeled, programmed, and experimentally optimized. By reconstructing cellular behaviors outside the framework of existing organisms, we aim to reveal how life can emerge from seemingly lifeless molecules. Key topics include:

Control membrane growth, deformation, and division using protein-based molecular machinery
Coordinate genome replication with compartment division to enable inheritance across synthetic cell generations
Develop predictive models and design principles for the iterative construction of synthetic cells