Aims of MaxSynBio Network
What drives us further
The research program of the consortium „MaxSynBio: Max Planck Research Network in Synthetic Biology“ relies solely on the bottom-up approach in Synthetic Biology. It is focused on the detailed analysis and understanding of selected essential processes of life, via their modular reconstitution in minimal synthetic systems. The fundamental insights gained from the reconstitution activities, on the long-term perspective, should be utilized for establishing a new generation of biotechnological production processes which would work with synthetic cell constructs replacing natural living cells used in conventional biotechnology. Thus, both aspects - gaining fundamental insights as well as seeking potential applications - are the motivating driving forces for the MaxSynBio consortium.
In order to reduce the complexity of the objects of investigation, we do not aim at the reconstitution of a fully functional synthetic cell.
Instead, the consortium is concentrating intentionally on the synthesis of selected life processes which are of fundamental importance for the proliferation of living cells, more specifically:
- Energy: All active processes in living systems need continuous supply of energy and materials, either harvested from the extracellular environment or transferred from other parts of the systems. In many cases, energy supply and storage is closely connected to thecell’s metabolism, i.e. to the enzymatically controlled conversion of energy into chemicalsubstances required for certain cellular processes and subsystems, or the conversion of nutrients into readily available energy components needed for performing cellular functions.
- Metabolism: Metabolic processes are of special interests since they promise an interesting potential for industrial production processes. Metabolic reaction cascades and networks in biological cells are of impressive complexity. In MaxSynBio we aim to reconstitute a fully functional metabolic cascade while reducing its complexity to a minimum. As a proof of principle but also to demonstrate a practical application we have chosen the CETCH cycle, which captures CO2.
- Growth: The term growth is used here in the context of cell development, i.e. it refers to the increase in volume of a single cell. It is a very important part of the proliferom.
- Division: A mother cell divides to produce two daughter cells. Before division can occur, the genomic information stored in chromosomes must be replicated, and the duplicated genome must be separated between cells. One type of division mechanism is binary fission where the genetic material is segregated equally into two daughter cells. In order to divide, a cell has to be polarized. Cell polarity refers to spatial differences in the shape, structure, and function of cells. Almost all types of cells form polarity patterns which enables them to carry out specialized functions.
- Signaling & Motility: Along with the control of cellular growth and differentiation, morphogenesis is one of the fundamental aspects of developmental biology. It causes a cell or an organism to develop its shape. Morphogenetic responses can be induced e.g. by environmental chemicals or by mechanical stress caused by spatial patterning of cells. Many living cells are able to detect changes of the physical and chemical environmental conditions, transmit external stimulus signals and initiate a spontaneous and active response behavior, e.g. adhesion on surfaces or directed movement within their environment.
In the context of MaxSynBio, we summarize the entirety of the just mentioned life processes under the term “proliferom”, because - in a more general sense - all these processes are linked to the proliferation phenomenon. The proliferom is based on two major prerequisites:
- Compartmentalization: Nearly all processes in living cells take place in microcompartments consisting of membrane structures functionalized with embedded proteins which enable or control many different processes in cells, such as transport, catalysis of reactions, energy transformation, signal transduction and many others. Consequently, synthetic life processes must be reconstituted in cell-like synthetic microcompartments.
- Proteins Expression: The key molecular devices within functionalized compartments are proteins, particularly membrane-bound and membrane-integrated proteins. The transcription-translation machinery of cells transfers genetic information into functional proteins. The ability to run this machinery under well controlled conditions is of paramount importance for the realization of minimal life systems.
In MaxSynBio, functionalized cell-like containers, equipped with energy supply and metabolic modules, are to be used for mimicking essential life processes. For the reconstitution of these processes, minimal systems are to be assembled from functional modules, which in turn are composed of parts. These parts are built from molecular entities. Thus, our modular bottom-up approach is based on four hierarchical levels, namely systems, modules, parts and molecular entities. Prior to the design of a specific system, the desired system functionality must be clearly defined. Once this is fixed, a construction plan of the target system can be prepared from which all functional modules and parts, needed to fulfill the system’s functionality, can be derived. Based on the list of parts, it can be decided which molecular entities and structures (natural and/or non-natural) are to be used for realizing the functionalities needed on the parts level.
On the long term, we are aiming at the true computer-aided design procedure, i.e. artificial life systems should be assembled from parts and modules by use of standardized libraries. In parallel to the experimental implementation of a given construction plan, the computer aided system analysis based on mathematical models should be performed. Thereby competing systems designs are be evaluated, e.g. with respect to stability and robustness, and necessary additional functional modules can be identified. The cyclic workflow from the experiments via modeling to the systems analysis and back to system design should be supported in a flexible manner by computer toolboxes to be developed in MaxSynBio. The just sketched computer-aided modular cell design is another important long-term goal.
A rational synthetic approach towards creating living systems, as pursued by the MaxSynBio consortium, has potentially huge ethical and societal implications. Thus, it is indispensable to integrate in our research program activities aiming at investigating all ethical issues and dealing with the public communication of the research performed in MaxSynBio.
(1) monitoring of advancing scientific steps, e.g. related to safety issues and security concerns,
(2) reflection on methods, themes and outcomes of ethical and societal dealings with Synthetic Biology,
(3) analysis of imaginations, interpretations and framings prevalent in the general public,
(4) engagement of public with science via open communication platform,
(5) theoretical modelling and empirical ground work on different concepts of Synthetic Life,
(6) development of strategies for responsible government addressing concerns of “dual use” and “bio-patenting”.