CellComp

Cellular Computing

The Cellular Computing team is an interdisciplinary research team that combines experimental and theoretical methods to improve the design and engineering of biological systems across scales.

Manish Kushwaha

The Cellular Computing team aims to engineer synthetic genetic circuits with increasing levels of complexity: going from the molecular-level in cell-free systems to the multicellular level in co-cultures, with intercellular exchange. By integrating experimental data with mathematical modelling, we strive to understand and predict the behaviour of these circuits, facilitating optimisation and scaling up. Finally, we will use the knowledge generated to improve computer-aided design and automate the process of designing new genetic circuits with diverse functionalities, and across diverse organisms. Our long-term vision is to advance the field of synthetic biology and pave the way for transformative applications in bioengineering and biotechnology. For details, see: https://www.cellularcomputing.team/

Research axis

CellComp axis 1 - Genetic Circuit Design As synthetic genetic circuits grow in scale, they become increasingly difficult for the host cells to maintain and run. The cellular resources required for these circuits impose cellular burden and make the circuits susceptible to negative selection that results in their loss. In this research theme, we build experimental and theoretical methods for quantifying and reducing the expenses/ burden associated with circuit maintenance and execution, as well as mitigating circuit burden using resource-aware dynamic feedback control. Using these methods, we aim to identify the most efficient design architectures that enable the implementation of genetic circuits with defined functions, while minimising expression costs.
CellComp axis 2 - Distributed Bio-computing To circumvent the size-limit on scaling up of genetic circuits inside single cells, multicellular approaches for building distributed biological circuits have recently emerged. In this research theme, we develop approaches to enable synthetic cell-to-cell communication within bacterial communities, including the accompanying computational logic. These engineered communication signals will enable scaling up of multicellular circuits for complex computational tasks, using a combination of small molecules and DNA-based high bandwidth signals for intercellular communication, implemented in several different environments.
CellComp axis 3 - Multi-species Circuits The lack of genetic tools in useful non-model organisms currently prevents leveraging the full potential of the biotechnological process. Considerable effort is required to identify and characterise new genetic parts before they are for engineering in a new chassis organism. In this research theme, we develop cross-system compatible genetic tools and expression systems that are “portable” between different types of cellular and cell-free systems. We use these portable parts for rapid prototyping of genetic circuits and metabolic pathways in a cross-system manner. The aim is to expand the genetic circuits from a single species at-a-time to systems with cells from multiple species: including those from different kingdoms of life.

The lack of genetic tools in useful non-model organisms currently prevents leveraging the full potential of the biotechnological process. Considerable effort is required to identify and characterise new genetic parts before they are for engineering in a new chassis organism. In this research theme, we develop cross-system compatible genetic tools and expression systems that are “portable” between different types of cellular and cell-free systems. We use these portable parts for rapid prototyping of genetic circuits and metabolic pathways in a cross-system manner. The aim is to expand the genetic circuits from a single species at-a-time to systems with cells from multiple species: including those from different kingdoms of life.

Team members

Thomas NOWAK

  • Scientist

Matthias FÜGGER

  • Scientist

Manish KUSHWAHA

  • Scientist

Shreyas PARKHIE

  • PhD student

Anchita SHARMA

  • PhD student

Maud HOFMANN

  • PhD student

Abhinav PUJAR

  • PhD student
  • Dominique LE COQ (CR CNRS)
  • Jean-Christophe PIARD (IR INRAE)
  • Cédric Saint Martin (PhD)

Key points

News

  • PhD defense

Abhinav PUJAR – 10/04/2025

Distributed Biological Circuits in Synthetic Phage-Bacterial Systems
  • Research article

Phage-mediated intercellular CRISPRi for biocomputation in bacterial consortia

In the field of Synthetic Biology, biological systems are engineered to sense inputs and respond in a programmed manner, a process called biological computing. Traditional biocomputing faces limitations due to the resource burden on single engineered cells, restricting the amount of foreign DNA they can simultaneously express. A recent solution, distributed biological computing, involves using […]
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