Light Tube Array for Genetic Circuit Design

Rice University bioengineers have developed an ultra high-precision method for creating and measuring gene expression signals in bacteria by combining light-sensing proteins from photosynthetic algae with a simple array of red and green LED lights and standard fluorescent reporter genes. By varying the timing and intensity of the lights, they were able to control exactly when and how much different genes were expressed. "Our work was inspired by the methods that are used to study electronic circuits. Electrical engineers have tools like oscilloscopes and function generators that allow them to measure how voltage signals flow through electrical circuits. Those measurements are essential for making multiple circuits work together properly, so that more complex devices can be built. We have used our light-based tools as a biological function generator and oscilloscope in order to similarly analyze genetic circuits," says Rice bioengineer Jeffrey Tabor.



Transcript

00:00:01 [Music] in our lab we engineer living cells like bacteria to do useful types of functions for people so for example to sense the chemical signals of disease uh in your body and respond by producing molecules that prevent the disease and the way that we do that is to actually build little circuits made of genes inside of these bacteria and the circuits uh are

00:00:29 are responsible for during the Computing they actually allow the cells to uh detect complicated signatures of disease in your body and respond only at the right time in place and only deliver uh the correct amount of of a drug it's very difficult to build these circuits and we build small components of the circuits but it's very difficult to put them together and have them perform

00:00:51 predictively like they do in electrical engineering what we did here is develop a new method where we could actually use light visible light uh as a signal uh much like an electrical uh device called a function generator where we can send um time varying signals uh that go up and down into these circuits at different speeds and then um by measuring how the circuit responds to

00:01:14 these light signals uh we can actually uh understand how the circuits behave uh which allows us to to use computer tools to to build larger circuits in a more predictable way we needed a device to shine light on on our cells in a you know precise Manner and there wasn't really anything available on the market to do it we we decided that we would build our own Hardware the design has

00:01:37 four LEDs underneath each culture tube uh and they're all optically isolated from each other there's 64 tubes uh so there's a total of 256 LEDs that are all being controlled uh each one each LED can be uh controlled both in time and in intensity there are 496 different levels of intensity um and the refresh rate on on the apparatus is about 500 HZ the way that weed use the device is we take our

00:02:01 cells uh and we grow them up uh and we split them across all 64 tubes uh and then we run the experiment uh and let the cells grow under our pre-programmed light condition uh and uh they they'll grow for eight hours then we remove them all and and we take them over to another instrument for measurement so rice is in a really special location so we sit next to the world's largest Medical Center

00:02:24 and uh rice is an engineering school and we've we've got uh multiple faculty now who are studying Sy itic biology we have a great opportunity uh to build um medically relevant Technologies out of living organisms and then work with the medical researchers across the street to actually test those and push them through into clinical applications uh very quickly and so um for example we're

00:02:48 engineering bacteria that could diagnose disease signatures in your body much more accurately than current Diagnostics can do and at much lower or much earlier in the progression of the disease and we have collaborators in the medical center who can literally walk across the street hand them our engineered bacteria and they can test it in in Mouse models and animal models very quickly and tell us

00:03:07 if it works or fails and then uh right across the street back in our lab we can quickly make a new design or fix our design and send it back to them so rice is very uniquely positioned to make a lot of uh Headway uh in in the medical applications of synthetic biology