SEED 2015 - Microfludics for Synthetic Biology!

µsynth: A Versatile Microfluidic Device for Automating the Synthetic Biology Process

- by Steve Shih, JBEI

Steve Shih’s very well structured talk gave a concise and intriguing peek into the world of microfluidics and its promising potential in synthetic biology automation. In reference to his work he said that Synthetic Biology could be defined as the science to “design and build genetic circuits in living cells.” There is an inherent circular process in every synthetic biological experiment – design and selection of a particular target->build parts of the circuit or pathway as well as perform the actual microbial transformation to run the selected biological circuit->test the resultant engineered microbe using standard validation techniques->learn and repeat the step for optimization.

Microfluidics has been around for a long time and the technique has diversified into a wide range of types (microchannels, two-phase flow, paper fluidics, slip chips, to name a few), all allowing the controlled and regulated interaction of multiple fluids. In case of synthetic biology, microfluidics may hold the key to expediting and automating the experimental cycle described above. They will be able to integrate all chemicals and microbes onto one tiny handheld device, reminiscent of “lab-on-a-chip”.

Shih proposed a novel microfluidic device that controls the flow of liquids in various channels with the help of electrodes. The technique – called Digital Microfluidics (DMF) – harnesses the inherent ionic nature of different fluids and controls the motion of tiny droplets out of the device’s reservoirs and into the common mixing channels to prepare micro-solutions with extremely high efficiency and reproducibility.

The DMF is essentially a layer of alternating electrodes and insulators topped with a hydrophobic surface that contains the reservoirs and fluid channels. Each DMF device can be plugged to a computer and fed with a simple program that will sequentially mix different constituents of an experiment automatically. In his presentation, Shih also demonstrated a successful proof of concept using a bicistronic design. Looking forward to more widespread use of DMF devices in the future!

Their lab website: http://www.jbei.org/research/divisions/technology/microfluidic-assays/

SEED 2015 - Jeff Way, Wyss Institute - Spatial and Quantitative Optimization of Engineered Multi-Element Therapeutic Proteins

Dr. Jeffrey Way started off session 2 on biomedical applications at the SEED (Synthetic Biology: Engineering, Evolution and Design) conference by talking about the application of synthetic biology in protein drug design and production.  Protein drugs are essentially drugs that either target proteins thereby blocking their activity or replace a missing protein (as in case of diabetes or anemia).

Dr. Way discussed how nature uses highly complex systems to achieve immune responses – multiple proteins interact with multiple ligands and this complex network is constantly edited by evolution.

At its core, Synthetic Biology is about learning from Nature and improving our methods of producing organic compounds. Borrowing a leaf from redundant and complex mammalian pathways Dr. Way proposed to improve specificity of protein drugs in two ways – first, by introducing minor mutations in the proteins such that their affinity to bind to non-targets reduces, albeit at the cost of 40x-200x reduction in target-specific activity and second, by physically linking the protein to another protein that will bind to a spatially nearby cell-surface receptor.

Dr. Way and others in the Dr. Pamela Silver lab have demonstrated the aforementioned strategies using two protein drug systems – the IFNα and Erythropoietin (EPO). This technology holds promise in the billion-dollar field of EPO production – the key drug for anemia - but work needs to be done in making this suitable for scenarios such as “solid” tumors that are rendered inaccessible due to lack of proper exchange of fluids with lymph nodes and are impervious to diffusion.

To address the current challenges in protein drug design, Dr. Way urged the need for computational tools that would allow spatial optimization of protein-protein complexes and increase the throughput of the current method of experimental trial and error.

For more information, visit their lab site: https://silver.med.harvard.edu/