Week 10: Bioproduction

Using Gynkgo Bioworks foundry resources in our final project

My final project

For my final project I am desining a E.coli or S. cerevisiae strain that can detect COVID-19 so that it can be deployed anywhere without expensive resources.

In order to do that, I am trying to make my organism express ACE2 and link binding of viral spike protein to ACE2 with an intracelullar cascade signal that produces a compound. So far I have not been able to find the intracellular cascade pathway that viral binding to ACE2 triggers, probably because ACE2 just helps the virus fuse with the cellular membrane.

Therefore I will try to express a few proteins in E. coli or S. cerevisiae.
-First, a chimeric ACE2 linked to a detection mechanism through quenching fluorescence or quorum sensing.
-Second a protein similar to the virus spike protein so that it binds it with less afinity to ACE2 than COVID-19

How I will leverage Ginkgo's resources

The first thing I need to do is the design of the proteins. This can be done much faster using Gynkgo platform because they can support the lead optimization of different protein designs. For example, they can do rapid DNA synthesis that I could leverage to generate hundreds of different protein designs. They mentioned they have a protein engineering pipeline so I could leverage their capabilities to further improve key parameters such as sensitivity of my protein.

Second, I could also use their DNA synthesis capabilities to synthesize cell plasmids with the required components that I need in my genetic circuit and that I will later use to transform my cells. Each of those plasmids will include different variants of my protein designs, as well as different detection mechasnism that I want to test. Without Gyngko's capabilities, I would have to do each of them one by one, so I could not try as many designs. However, this way, I could try to test as many as possible to find the one that works better

Third, I will need to clone those proteins inside E.coli and/or S. cerevisiae, so I could use their automatic processes to accelerate the transformation of my strains and also their strain selection or large-scale sequencing capabilities to select those that I am most interested in (eg. best expression of ACE2)

With all of those large-scale screening, I would easily accelerate the process of synthetising my genetic engineered organism because I could just do massive screening with different designs and different strains instead that trying over and over again until it works