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Using natures command and control network to develop ways to engineer organisms

Virginia Polytechnic Institute And State University : 09 September, 2002  (Technical Article)
Peter Kennelly, a professor of biochemistry at Virginia Tech, is probing nature's own command and control network to understand how it functions and to develop new strategies for genetically engineering organisms. By mapping the mechanisms already in place to find the switch that controls a certain action, Kennelly is working to find ways to turn on processes that normally would not be active.
'Living organisms do an amazing amount of chemistry,' says Kennelly. 'The goals of life sciences are not only to take advantage of that machinery, but to control it so it can do more sophisticated tasks,' he says. 'Currently when we want a desirable trait in an organism, we introduce a gene that we put under artificial control to make a large quantity of the protein product of that gene.'

The protein forces the organism to perform the desired task, but this is an inefficient and stressful method because it requires cells to produce hundreds of times more protein than is needed. 'We tend to stress the organism because it has to use most of its resources to do the task,' he says.

In contrast, turning on a specific switch already in place within the organism is more efficient and economical because the response is more proportionate. The maintenance of a more balanced distribution of resources among cellular processes also makes the organism more viable and robust. One application of the new method is in the development of biosensors, enzymes that are intermediaries in the natural sensing of outside events.

'If we did this from scratch, it would take us a long time, but we're able to do it more quickly if we take advantage of nature's existing engineering and modify it,' Kennelly says.

He likens the way he works to the process used to develop airplanes, in which inventors looked at birds for the basic components and then modified those parts to work in something man made.

Events taking place within a cell are linked together in networks that allow the cell to process information and make a 'decision' about what to do (the response.)

'As we learn more about how the networks perform, we can engineer them to be more sophisticated, efficient, and adaptable,' he says. For example, Kennelly's collaborator, Professor Malcolm Potts of biochemistry, works with cyanobacterium. These organisms make a protective carbohydrate material that helps the organism survive drought, temperature extremes, and radioactivity. In the future, they hope to find a way to not only use this type of coating as protection, but also to engineer it to be self-renewing and adaptive.

'What if we could embed that microorganism in the coating on the hull of a ship?' Kennelly asks. 'It would provide excellent protection because it can survive a long time. And since it's photosynthetic, it just needs light and air to perform useful tasks. Imagine if we engineered it so it knows that the coating is wearing out, and makes more when this occurs. It also could change as needed depending on the temperature and other conditions.'

In a sense, Kennelly says, it's like going from controlling a stereo system by just plugging and unplugging it to being able to manipulate the bass, treble, balance, volume, and all other control systems. 'We're going to be able to modify it to meet our needs and fine-tune each system the way we want it. We'll not only get something in between off and full volume, but we also can manipulate it to very specific tasks. This is what the next generation of genetic engineering will be. In our lab, what we're doing is learning what the parts are so that we can learn how to control them.'

The mechanism is a fundamental target of medicine. 'In the future, artificial cells could be engineered that will sense when your body needs something and then supply it,' Kennelly says. 'For example, we could place a microbe inside people or animals that makes an antibiotic when the need is sensed, or that engineers an artificial pancreas that knows when to turn on and off, since you can't just make insulin all the time. This is a dream for the future.'

Kennelly has been working in this area for 23 years, starting as a graduate student. His interest in science began when he performed research as an undergraduate. His current research is supported in part by a $715,400 four-year NIH grant, a $273,900 NSF three-year grant, and a Hatch grant from the university's College of Agriculture and Life Sciences, which has just been renewed.
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