2. Network objectives

RoSBNet brings together people working in Synthetic and Systems Biology as well as systems/ control, electrical, chemical and computer engineers, physicists and mathematicians to address the theoretical and practical challenges of designing new robust biological networks or modifying already existing ones, which have to function inside uncertain biological environments, all the way from parts to whole systems. The network will also focus on the ethical, societal and economical concerns that are raised by advances in Synthetic Biology, aiming to create a fruitful discussion on how such concerns can be balanced by the potential usefulness of the many applications, such as environmental cleanup, fuel generation and healthcare. The objective is to transfer knowledge and develop a fruitful discussion and cross-fertilization of ideas on modelling, analysis, design and construction of synthetic biological networks, and to promote mobility and communication between control/ electrical/computer engineering, biology, mathematics and the social sciences as well as with Industry. The goal is to create a cohesive community that can effectively respond to research challenges, funding opportunities and international activities.

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5. Touching on ethical, legal and social issues (ELSI)

A constructive dialogue around Synthetic Biology may be hindered by the breadth of activities and the lack of a universal and single definition of “Synthetic Biology”, e.g. perceptions of scientists “playing god” in creating new life, intentional/accidental release of synthetic organisms, misuse to create biological weapons by biohackers, commercial race to synthesize and privatize synthetic life, etc.. People may treat synthetic life forms as dangerous until disproven. Also, current patent law may stifle collaboration and development and overcomplicate the patent process. These issues will be discussed in the network. In the first year, we will look at social and institutional implications of Synthetic Biology on researchers that work in multidisciplinary areas, ethics of genetics and gene therapy, and philosophical ethics. In the second year, the conceptual foundations and epistemology, legal/economic aspects of corporate partnerships, and ethical and social dimensions of biomedical science will be focused. In the third year, we will talk about ethical issues of building artificial life & interfering with nature, policies for biosafety and biosecurity, and legal aspects of biomedicine, etc..

3. Research challenges

Robustness is an important property which facilitates a synthetic biological system to maintain its designed performance within uncertain working environments. However, the term “robustness” is actually highly specific to the hierarchy level of the organisational scales. Making each parts/components in a large pathway working robust to its own function does not necessarily guarantee the robustness to the function of the whole pathway. On the other hand, the robustness to the function of each lower level parts/components may not be essential for the robustness to the function of the higher level network. Moreover, in some cases, the robustness renders the system resistant to intrinsic and extrinsic noise but at the same time it makes any attempt to tune the operating point so as to achieve a desired input-output performance for a particular application very difficult, if not impossible. All of above suggest that an adequate robustness level should be carefully adopted in every organization levels when design a synthetic biological network for any specific application purpose, and thus let the idea of simply interfacing lower level parts/ components to create higher level functionality with robustness still remain a challenge in current stage.

6. Management and activities

RoSBNet is co-funded by BBSRC, EPSRC, ESRC, AHRC in UK. Membership is dynamic via subscribing the mailing list, introducing self to other members, and contributing to discussions. A network core will manage membership and coordinate activities. The main activity is an annual, 3-day workshop. This will be open to all researchers. The organisation of the topics of the workshop is shown in the figure above. Funding is available for travel and subsistence for 30 Oxford-based, 20 Nation-wide/EU and 10 International members who will attend the annual workshop.

For more details, please visit the website

http://www.eng.ox.ac.uk/control/RoSBNet

, and welcome to join the mailing list

rosbnet-subscribe@maillist.ox.ac.uk

References[1] E. Andrianantoandro et. al., Molecular Systems Biology 2:2006.0028, 2007

[2] D. Baker et. al., Scientific American 44-51, 2006

[3] D. Endy, Nature 348:449-453, 2005.

1. Background

Synthetic Biology is a new research field which aims in designing new or modifying existing biological pathways in order to produce systems with superior or different properties, usually for a novel application. However, these designs need to be implemented inside a cellular environment and a major challenge of synthetic biology is that the effect of the interactions of the new pathways with the cellular environment need to be taken into account during the design or redesign process. This is unlike any other engineering design procedure, such as electrical circuit or computer engineering design, where the behaviour of simple parts, of more complicated components or even of whole systems, can be predicted and eventually measured and verified after implementation. This unique feature to Synthetic Biology designs poses new challenges. Many engineering/physical/mathematical disciplines have long been dealing with the analysis and design of complex systems that operate robustly in uncertain environments, and therefore have a lot to contribute towards constructing synthetic biological networks, whether these are parts, pathways, cells or multi-cellular systems, with performance guarantees within an uncertain environment.

4. Organisation of the topics

The figure above shows the organisation of the topics that will be investigated in the following three years. The challenge is to exchange views and expertise on how to construct robust biological networks at different organisational scales. From the Biology side, in the first year we will look at the level of simple functional network motif, in the second year at the level of large signal transduction/metabolic/ protein-protein interaction pathways, and in the third year at how whole cells can be constructed. At the same time, every year we will be looking at paradigms from Electrical and Computer engineering that are directly related to the biological scale – resistors/ capacitors/inductors and small circuits (op-amps, transistors etc) in the first year, larger circuits in the second year, and protocols/modularity/architecture of computer networks in the third year. In parallel to these, there will be a control/mathematical direction which will discuss modelling for design at these different organizational levels. Two common themes for all three years will be measurement – i.e., the methods/devices that evaluate the performance of designs – and ELSI, i.e., the ethical, legal, social, philosophical, economical and other issues raised by Synthetic Biology researches.

Increasing Hierarchy of Organization

Year 1 (2008-09)“Low Level” Structures

Biology Theme:Constructing simple functional network motifs (switches, oscillators, etc.) from standardised biological parts.

Electrical/Computer Engineering Theme:The “Art of Electronics” - building transistors, op-amps etc.

Control/Systems Engineering Theme:Understanding the robustness of simple biological and electrical circuits.

Year 2 (2009-10)“Medium Level” Structures

Biology Theme:Constructing and modifying signal transduction, protein-protein and metabolic networks.

Electrical/Computer Engineering Theme: Interconnecting parts to build circuits that perform efficiently and reliably.

Control/Systems Engineering Theme: Interconnection of subsystems to design robust super-systems; modularity in design.

Year 3 (2010-11)“Higher Level” Structures

Biology Theme:Bottom up and top down approaches for constructing artificial cells and multi cellular systems.

Electrical/Computer Engineering Theme:Organizational principles and protocols in computer networked systems.

Control/Systems Engineering Theme: Modelling, analysis and architectural principles of complex networked systems.

Network Challenge: Building robust synthetic biological networks across organizational layers

Universal Topics and Common Bases

Measurement methods at different scales and organizational levels. Ethical, economical, philosophical, legal and societal issues.

RoSBNet: From Robust Synthetic Biological Parts to Whole Systems: Theoretical, Practical and Ethical Challenges

1Oxford Centre for Integrative Systems Biology, Department of Biochemistry, and 2Control Group, Department of Engineering Science, University of Oxford, UK

Yo-Cheng Chang1,2, George H. Wadhams1, Judith P. Armitage1, and Antonis Papachristodoulou2*

Website: http://www.eng.ox.ac.uk/control/RoSBNetMailing list: rosbnet-subscribe@maillist.ox.ac.uk