Fostering synthetic biology automation through standards.

Synthetic biology aims to make it easier to engineer biology to carry out useful tasks. The field has effectively outplaced the virtually abandoned field of genetic engineering. This is being done by introducing genuine engineering notions such as design, modularity, standardisation and orthogonality; and, most importantly, the inclusion of mathematical modelling and computational simulations. DNA fragments are assembled in a Lego-like fashion to build biomolecular networks à la carte - the so-called 'genetic circuits'. Such circuits can mimic the functioning of basic electronic devices, for example, making bacteria behave as living computers. Over the last 15 years, several genetic circuits have been successfully engineered to make bacteria perform computational functions such as Boolean logic gates, counters, half-adders or memories.

A major limitation to engineer increasingly complex devices is the highly inefficient and nonstandard design process. Like any other engineering field, design precedes implementation/synthesis and testing. The more accurate the design is, the more robust and predictable the genetic device would be. However, there is a lack of tools to capture the information of designs, which are often sketched by hand with no computer intervention - a very error-prone method. Furthermore, design information is often not exchanged - another obstacle to the progress of synthetic biology. To fill this gap, the Synthetic Biology Open Language (SBOL), an open standard for the representation of in silico designs, is begin actively developed. By using SBOL, scientists can unambiguously describe DNA sequences. SBOL provides a data format that can capture information of complex systems in an unprecedented level of detail.

This Ph.D. project will focus on the research and development of novel advanced design methods for synthetic biology. A key objective is to develop new computational approaches for integrating experimental characterization (testing) approaches into standards such as SBOL. This will pave the way to what we refer to as functional standard design. This is, designs will not only embed information about DNA sequences but also about the performance of those sequences once inside a living organism. Furthermore, the project aims at establishing design rules among functional DNA components based on their characterization - a language to relate such DNA components will be developed to automate the process that goes from conceptualization to testing, through design. The approach to the research will revolve around genetic circuit design and simulation. Validation of in silico designs will be carried out through implementation and testing. The candidate will spend 3 months in the DOULIX TM headquarters (Venice, Italy) to learn the internal workings of an industrial interdisciplinary team and will also research the use of robotics and automation platforms for testing synthetic bacterial systems.