Strategies for spatial and temporal control of gene expression in cell-free reactions and biomimetic systems

• Applicant: Professorin Dr. Henrike Niederholtmeyer
• Subject Area: Biochemistry
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 436921284

Living Organisms control precisely where and when certain processes happen in their interior. Multicellular Organisms are built from specialized tissues, organs and structures that grew from a single cell during their development. Even single cells contain complex nanomachines, organelles and reaction networks, that execute reactions and determine at what location and at what time these reactions take place. In comparison to human-made technologies and machines, biological systems self-organize, grow, repair themselves and reproduce, and do so in a very robust manner. In combination with synthetic materials, these properties could have great advantages in our technologies. Our understanding of how self-organization works and is coordinated in living organisms is still incomplete and definitely not advanced enough to use these mechanisms efficiently. Biochemical experiments on purified enzymes and on isolated molecular processes have elucidated functions of biomolecules and the fundamental biochemical processes in cells. The advantage of experiments on minimal, defined systems is that their contents and their respective concentrations are known, and can be adjusted easily. In this project I will use a similar approach to investigate mechanisms that lead to spatial and temporal self-organization. Self-organization processes are a defining characteristic of all living things. However, they are counter-intuitive because they happen far from equilibrium and because they create order from chaos or homogeneity. Therefore, a synthetic bottom-up approach is necessary. Only when we can program, control and reconstruct self-organization processes in a biochemically simplified, defined system, we may fundamentally understand them. My approach uses cell-free gene expression and artificial materials that emulate cellular membranes and organelles. The goal is to develop genetic networks and molecular control strategies that lead to the formation of spatial and temporal patterns in gene expression. I will use specific binding interaction to control the availability and the diffusion of genetic regulators. For the realization of the project I will develop and use microfluidic technology to precisely control reaction conditions, as well as synthetic materials to spatially structure biomimetic systems. The insights of this study will lead to a better understanding of pattern formation in the development of multicellular organisms and enable us to use self-organization processes in artificial, biomimetic systems to our advantage.

• DFG Programme: Independent Junior Research Groups
• Major Instrumentation: Microscope
• Instrumentation Group: 5000 Labormikroskope