Full Programme

DNA origami, in which a long scaffold strand is assembled with a large number of short staple strands into parallel arrays of double helices, has proven a powerful method for custom nanofabrication. Although diverse shapes in 2D are possible, the single-layer rectangle has proven the most popular, as it features fast and robust folding and…

DNA origami, in which a long scaffold strand is assembled with a large number of short staple strands into parallel arrays of double helices, has proven a powerful method for custom nanofabrication of shapes up to 100 nm in size. However, the scaffold represents about half the mass of an origami, therefore the origami size…

Self-assembling protein containers are promising delivery vehicles for cellular and gene therapy applications, but the ability to predict how mutations alter self-assembly and other particle properties remains a significant challenge. Here, we combine comprehensive codon mutagenesis with high-throughput sequencing to characterize the assembly-competency of all single amino acid variants of several self-assembling proteins, including those…

In this lecture we will discuss the design of algorithms for the dissection of regulatory networks, including ARACNe, for the reverse engineering of transcriptional networks, MINDy, for the reverse engineering of signal transduction networks, and PrePPI for the dissection of protein-protein interaction networks using protein structure information. We will then address the use of regulatory…

Protein production is a multi-billion dollar industry, with applications in pharmaceuticals, industrial enzyme use (eg in laundry detergent), and biomaterials. Bacteria are receiving renewed interest as protein production hosts because of their fast growth and tractability. The Salmonella enterica Type III Secretion System secretes non-native proteins at product titers of up to 400 mg/L in…

In this second lecture we will discuss how network-based methodologies can be used to systematically identify, validate, and pharmacologically target of a new class of therapeutic targets represented by Master Regulator proteins, whose concerted aberrant activity within tightly regulated modules (tumor checkpoints) is responsible for the mechanistic implementation and maintenance of specific tumor cell states. These…

Systems and synthetic biology deal with substantial challenges due to uncertainty that more traditional disciplines such as physics or engineering do not face to the same extent. This has two main reasons: (i) despite the increasing availability of quantitative datasets, our knowledge about essentially all cellular networks is incomplete, regarding quantitative parameters and functional relations…

Synthetic biology has emerged as a novel discipline that tries to engineer biology in a more controllable, predictable and standardize manner. Bringing such characteristics to microbial systems allow us to expand the tools available to engineering metabolism in a more powerful way. This talk will present through some examples, how cutting-edge synthetic biology tools such…

A key step for understanding heterogeneity in cell populations is to disentangle sources of cell-to-cell and intra-cellular variability. Single-cell time-lapse data provides potential means for this, but single-cell analysis with dynamic models is a challenging open problem. Most of the existing inference methods address only single-gene expression or neglect correlations between processes that underlie heterogeneous…

This lecture will introduce the principle of genetically-encoded biosensors and their applications in synthetic biology.  The various types of detection elements that can be used (nucleic acids, proteins, and whole-cells) and the advantages and disadvantages of different circuit designs will be discussed.  Examples from the recent literature will be used to illustrate the principles of…

After several decades of engineering microbes for biotechnological applications, we have realized that overengineer strains often present undesirable features that limit the improvement of current production systems. Moreover, natural systems evolve as ecosystems and not as an individual to allow better performance in the environment. The use of microbial communities in the food and feed…

This lecture follows on from part 1 to discuss the key performance characteristics of a genetically-encoded biosensor including signal-to-noise ratio, sensitivity, and dynamic range, as well as the design features that can be used to modulate these characteristics.  Basic models of biosensor circuits  will also be covered to enable students to gain an understanding of how these…

Genomics has undergone a resolution revolution, such that the nucleic acid content of individual cells are now sequenced routinely in high-throughput mode. Thus we can define the cellular composition of tissues in an unbiased and comprehensive way using single cell transcriptomics, revealing the molecular fingerprint of cell states and their predicted signalling circuits in tissues…

A common approach to create synthetic genetic circuits is to combine components that have been previously characterized in isolation. Within this approach it is certainly desirable that the behavior of components does not change upon composition. However, this is rarely the case as a module’s behavior is often context-dependent. Context-dependence arises from a number of…

In vitro directed evolution allows biomolecules with new and useful properties to be engineered—mimicking natural evolution on an experimentally accessible time scale by creating large libraries of DNA mutants using PCR and then carrying out a high-throughput assay for variants with improved function. To provide a breakthrough in the complexity of libraries that can be readily…

The fluorescent proteins revolutionized our ability to study protein function directly in the cell by enabling individual proteins to be selectively labeled through genetic encoding of a fluorescent tag.  As researchers seek to make increasingly sophisticated dynamic measurements of protein function in the cell to unravel molecular mechanism, we designed a chemical tag to combine…

In this lecture, I will present a general approach to ``isolate’’, to some extent, the behavior of a genetic circuit from context. Specifically, I will address two problems. The first problem is to enable a genetic circuit to drive arbitrarily large loads without compromising the quality of the signal being transmitted. To this end, I…