NU Engineer Reprograms Cells to Combat Malaria Worldwide

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Keith Tyo applies synthetic biology, genetically reprogramming cells, to combat global health crises such as malaria.

Malaria strikes nearly 500 million people and causes a million deaths every year, according to the World Health Organization.

Tyo, a chemical and biological engineer at Northwestern University, recently received a $100,000 grant from the Bill & Melinda Gates Foundation for his work. His global health projects focus on creating new compounds to treat a host of diseases, including HIV and tuberculosis. He plans to produce low-cost biosensors for underprivileged countries desperately in need of basic medical diagnostic equipment.

Keith Tyo specializes in synthetic biology, engineering cells that can provide inexpensive diagnosis and treatment for disease. (Photo courtesy of Keith Tyo)  Keith Tyo specializes in synthetic biology, engineering cells that can provide inexpensive diagnosis and treatment for disease. (Photo courtesy of Keith Tyo)

His prestigious award allows him to work on techniques in engineering biological systems to improve the quality of life for those around the world lacking access to basic medical care. One of his innovative projects involves engineering yeast cells as biosensors that can inexpensively diagnose diseases or even confirm pregnancy.

What is synthetic biology?
Synthetic biology is reprogramming cells by changing their DNA, with the goal of doing something useful for society. Synthetic biology is a field regulated by the government.

How do you use synthetic biology to address global health problems? What are some of these issues?
Synthetic biology is being able to reprogram cells. And you can use that for lots of things. I’m interested in combating poverty and the key challenges related to poverty that can be solved by technology. What we can do is look at ways of reducing the cost of health care delivery in resource-poor countries. In a developed world, we have hospitals and hospital labs with well-trained physicians and equipment. You don’t have that in resource-poor countries. We’re trying to take aspects of this hospital lab and program it into a cell, specifically a yeast cell - the exact same yeast you’d use to make your bread. By programming yeast DNA to be able to detect pathogens or other blood markers and having the yeast itself change colors, this could look like a diagnostic test, such as a pregnancy test. The strip is made of yeast, or has yeast on it, and yeast would change colors if you had a tuberculosis infection, or your iron levels were below a certain threshold, etc. Yeast is incredibly cheap. There are many drugs that we make now that are approved drugs that are known to be effective.  We are reducing cost of synthesis by using yeast as a factory; that is, using yeast cells as an actual way to convert raw material into a product. Through that, you can make compounds with much less starting material, so costs can go down.

You recently received a grant from the Bill & Melinda Gates Foundation to combat malaria. How do you plan to utilize these funds?
Three different Gates Foundation grants have been given to Northwestern University. We are looking at low cost synthesis of drugs for HIV, malaria and tuberculosis. The money is to support Ph. D. students to carry out the experiments that will test our different hypotheses about how synthetic biology will be implemented.

What will you be engineering in the case of malaria?
Parasites of malaria spread from human to human via mosquitoes. People are working on engineering sterile mosquitoes that can be made and released into the environment. When mosquitoes mate, they would mate with the sterile mosquitoes so that they wouldn’t be able to reproduce. Through this they could reduce the general mosquito population. This sidesteps the need for harmful chemicals and pesticides. We are looking at enzymes inside of malaria parasites and looking at enzymes that are essential for that cell to live. We are going to trick the plasmodium (microorganisms that cause malaria) into actually chewing up those essential enzymes, and by doing this trick of convincing the cell it’s a bad protein and chewing it up, it kills itself. This is a novel form of treating plasmodium, or malaria, and tries to kill plasmodium. My expertise is in which would be the appropriate proteins to chew up.

Many areas of the world are impacted by malaria and people anywhere can contract the illness when they travel abroad. But where are the key areas where we need to combat this disease?
Sub-Saharan Africa, primarily.

What would you like people to take away about your work and from the potential of synthetic biology?
Alleviating suffering. There are actually concrete opportunities to make technologies that would extend many of the great things we enjoy in this country in countries that don’t have it. That’s what I spend my days and nights thinking about.

How do you address concerns about misuse of synthetic biology?
There are regulations in place. All technologies with great potential have potential for both good and harm. How do we make bioethics an essential aspect of every Ph. D. program that does synthetic biology? By training the students to think well and to think about dual use and the implications of the research they do. Then there’s a much greater chance of self-regulation. President Obama has put out two reports related to synthetic biology and how people might be able to use this for harm, so there are regulatory bodies. It’s very much regulated.

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