High Throughput Synthetic Biology and Biosensors

Top

00:00:11.18 Hi, my name is Lauri and we're going to talk
00:00:13.23 a little bit about synthetic biology
00:00:15.17 and high throughput methods on how to create biosensors.
00:00:19.08 We human beings are really bad at sensing
00:00:21.25 weak signals in nature. We cannot see buried landmines,
00:00:25.13 we cannot smell polluting chemicals in nature,
00:00:29.01 we cannot taste toxins in our drinking water.
00:00:32.23 We have created really, really sophisticated
00:00:36.13 analytical methods to detect all of those things.
00:00:38.17 But those instruments are really expensive
00:00:41.06 and next to impossible to use in field.
00:00:43.12 For example, arsenic is a really common element in the soil,
00:00:47.18 but when it leaks into our drinking water, it becomes
00:00:50.20 a tasteless and odorless killer.
00:00:52.23 In western world, we can do analysis on our drinking
00:00:56.19 water and monitor the levels of arsenic.
00:00:59.05 So you can be pretty sure that the water you're drinking
00:01:00.28 is safe, but in the developing countries,
00:01:03.14 those instruments are not available.
00:01:06.13 The water is taken from wells and all the laboratories
00:01:11.06 are far away. So what we would need is a simple
00:01:14.10 kit that would be really cheap and easy to use,
00:01:17.02 that anyone can use to monitor the levels of arsenic
00:01:20.18 in their drinking water.
00:01:22.06 Now, what analytics is all about is
00:01:26.24 taking a weak signal and converting
00:01:29.07 it into something that we can see,
00:01:31.24 or detect. Microbes have evolved into
00:01:36.24 sensing their environment and reacting upon
00:01:39.01 it. So, if we could use the microbe to take
00:01:43.25 the input signal and turn it into something visible, like
00:01:46.16 light. That would be really handy
00:01:49.18 and you would call that a biosensor.
00:01:51.23 And now, the structures in the microbe that would do it
00:01:54.22 would require some part that takes the input signal
00:01:58.19 and then launches some kind of output signal.
00:02:01.08 This, we would call a reporter gene.
00:02:03.06 Reporter genes should be very sensitive,
00:02:07.19 it should detect really small amounts of the input signal
00:02:10.11 and it should also be very specific.
00:02:12.26 It should not react to just anything. Now
00:02:15.24 let's take a quick closer look into this promoter
00:02:17.29 part of the reporter. We could cut it down in smaller
00:02:23.05 parts, some of the parts would be responsible for binding
00:02:27.00 transcription factors, some other parts would be
00:02:30.04 responsible for binding polymerases,
00:02:32.17 and some other parts would be responsible for
00:02:35.02 binding ribosomes. There would also be some linkers
00:02:37.29 that would space those elements from each other.
00:02:40.07 Now we can rationally decide these parts.
00:02:43.13 Building all different kinds of variations,
00:02:47.02 and then combine them together into different
00:02:49.22 kinds of combinations. Now, we would pretty soon run into
00:02:54.28 a problem that we have many of these combinations
00:02:57.19 and that would result in a huge number of
00:03:00.13 samples that we should test. Essentially, that would
00:03:03.14 result in a huge number of microbes that we need to test
00:03:06.02 for, for their ability to function as a biosensor.
00:03:09.25 And that is something we can do with robotics.
00:03:13.12 Hi, my name is Angela. So in this experiment, we are
00:03:16.29 going to test different promoter constructs.
00:03:19.25 Since we are dealing with a huge amount
00:03:21.25 of different possibilities, we need to be assisted by
00:03:24.26 a robot to make it feasible. So basically, what the robot
00:03:28.16 will do for us is to introduce the different promoter
00:03:31.17 constructs into the bacteria. Then, we will test
00:03:34.19 the promoter activity by measuring the cell's luminescence.
00:03:38.26 Hi, I'm Claudia and in this experiment
00:03:40.25 we are interested in identifying a mutant
00:03:42.23 which shows stronger activity than the other potential candidates
00:03:46.07 strains to finally create a more efficient promoter.
00:03:49.01 So when we looked at the data, we saw
00:03:51.18 that if you completely destroy the promoter, you don't see any
00:03:54.13 activity, which is measured illuminescence compared to a white background
00:03:58.01 of potential strains which show relatively low
00:04:00.19 and comparable activity.
00:04:02.13 However, we were able to identify
00:04:04.04 one particular strain which showed very strong illuminescence
00:04:07.01 and is therefore a potential candidate for
00:04:09.08 further experimental follow-up.
00:04:10.28 Synthetic biology not only gives us the tools to create
00:04:14.10 all those combinations, but more importantly, allows us
00:04:17.22 to select from a huge amount of variation.
00:04:20.06 In this case, we could select the one microbe that
00:04:24.02 does the job for us, pick it from the sample,
00:04:27.12 and trace back the combination of elements that we
00:04:30.08 actually used to make it. In this case,
00:04:32.14 this specific combination allowed sensitive and very specific
00:04:37.18 detection of the input signal and a very
00:04:40.14 dynamic output signal. Now, this might
00:04:45.20 microbe could be used to create a sensitive,
00:04:49.13 cheap, and easy to use tester to make sure
00:04:53.13 that your drinking water does not contain arsenic.
00:04:55.28 This is not science fiction, this is done already
00:05:00.05 in several companies developing this technology.
00:05:03.04 Synthetic biology allows us to create these
00:05:08.00 biosensors for practically anything.

This Talk

Audience:

Researcher

Recorded: June 2015

Talk Overview

Humans are bad at detecting weak signals in the environment, for example sensing pollutants in the area or toxins in drinking water. Most instruments that have been developed to detect such signals are very expensive and cannot be used in day-to-day lives. Using synthetic biology, inexpensive and efficient biosensors can be created to detect weak signals and create a response that humans can detect, such as emitting light. Using engineering principles and robotics, the Synthetic Biology in Action participants describe the steps they used to optimize a biosensor to sense an environmental input and create the maximal response possible.