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Biochips in Bangkok: Thailand's Sole Array Lab Plows Ahead with Ag-Bio Projects


By Justin Petrone

BANGKOK, Thailand — Minimum input, maximum output. That's the credo of the microarray lab at the National Center for Genetic Engineering and Biotechnology, or BIOTEC, the biotechnology arm of Thailand's National Science and Technology Development Agency.

BIOTEC's microarray lab, the only lab of its kind in the country, was founded two years ago to focus on projects related to pathogen testing and agricultural research, but running an array lab in a developing country has its share obstacles, including a shortage of available funding, lack of experienced talent, and logistical headaches.

"If you order a chemical reagent in the US, it might take a day to get there, [and] if it gets there in three days it's considered late," Nitsara Karoonuthaisiri, director of the BIOTEC array lab, told BioArray News. "Here it can take 45 days. So there are a lot of difficulties to adjust to when running a lab here."

A chemical engineer who studied at Columbia University and later Stanford, where she trained in the lab of Camilla Kao, Nitsara was 29 when BIOTEC asked her in 2007 to start an array lab that could help support local research endeavors. Because Thai government policies favor ag-bio projects, that's where the lab focused its early projects.

"The government decided that Thailand wants to be the kitchen of the world, and we must support that policy because most of our funding comes from taxpayers," said Karoonuthaisiri.

For her lab, that meant shrimp research. "Shrimp is one of the most important animals for our economy," Karoonuthaisiri said. "We had a lot of programs to research shrimp, and array technology was seen as another tool" with which to study the crustaceans.

Two specific projects included making black tiger shrimp arrays for gene-expression profiling and for identifying probiotic bacteria to be used as shrimp feed. In both cases, BIOTEC researchers have been paired with their counterparts in industry to conduct the research.

"We have board meetings for the shrimp program that include the farmers. So they come in and say, 'Look, I really don't care about this molecular stuff, but here, this is a problem we see. We see that if the testes of shrimps are black then we can't use them,'" Karoonuthaisiri said. "Then as researchers we have to determine how having black testes could affect the offspring of the shrimp."

While there is interest within Thailand for researching black tiger shrimp, a larger variety of the species that demands a premium price, Karoonuthaisiri said there are currently no plans to sequence the organism's genome.

"Whole-genome sequencing costs a lot and we don't have a lot of resources," she said. "Plus, the black tiger shrimp genome is complex. It is estimated to be two-thirds the size of the human genome."

The array lab's main workhorse for its various projects is an Arrayit NanoPrint arrayer instrument. But before BIOTEC could procure the instrument for its shrimp projects, Karoonuthaisiri had to find other ways to make chips.

"Before we had the NanoPrint machine, I flew back to Stanford and Columbia to print the chips," Karoonuthaisiri said. "For the first version of the shrimp chips, before this machine was delivered, I had to fly to Columbia and print the arrays there. Without equipment and without infrastructure our researchers had to rely on other institutes."

Then there were the universal challenges. "To upgrade technologies in developing countries is hard because after a year a system is already obsolete," Karoonuthaisiri said, describing how she decided on the NanoPrint only after evaluating other options on the market. "When you make a purchase you have to make sure it has most of the features you need it for and to know that that technology is at a saturation point and that it's not going to change within three months."

Another technology obstacle for the lab was the local environment. "At Stanford, we built our own [arraying] machine and … the machine can be an open system because in California, it's 40- to 50-percent humidity all the time," Karoonuthaisiri said. "But, in Thailand, even with air conditioning on, humidity went up to 80 percent," she said. "So, what do we do? We have to have our [arrayer] in a humidity-controlled room."

Finding talented lab personnel was also challenging. "In the US there are hundreds of people who have worked with arrays, even more," said Karoonuthaisiri. In Thailand, "you can count on your fingers how many have made their own chips, maybe less than five," she said.

However, these challenges sometimes had a built-in silver lining: "Thais like us who come back to work in our country … become experts almost automatically and there are a lot of opportunities to work," she said.

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Food Testing

Besides shrimp research, BIOTEC's array lab has delved into food-borne pathogen testing, and has developed an antibody array approach to replace slower, more traditional methods like culture or multiplex PCR. BioArray News spoke with Karoonuthaisiri about the food-testing array last year (see BAN 8/11/2009).

Last week, she said that her lab is now trying to construct a higher-throughput detection system that can identify many food-borne pathogens. Currently, using the antibody array approach, Karoonuthaisiri's team can detect E. coli, Salmonella, and Listeria, she said. The lab previously established a proof of concept for the array by using it to detect pathogens in cow's milk.

Karoonuthaisiri and colleagues are now in the process of making the array applicable for different kinds of food, such as seafood, she said.

BIOTEC is cooperating with NanoAsia, a firm also based in Bangkok, to bring an automated instrument to market that will rely on the antibody array technology. The company has supported the project and wants to develop a low-cost machine that can be distributed to local food-testing labs, Karoonuthaisiri said.

"We are focusing on developing higher-throughput, lower-cost methods so that sensitivity will be better and [we are] also including a different set of antibodies so that [the] array can be more specific and [allow us] to check on different pathogens" besides E. coli, Salmonella, and Listeria, she said.

Karoounthasiri said that she plans to have a prototype ready that can be used by food-producing companies by the middle of 2011. "I don't think products can ever be finished, though," she said. "They are always being improved all the time."

Despite investments from firms like NanoAsia, most of the funding for BIOTEC's array projects comes from the Thai government. Last month, the array lab received an invention award from the Thai National Science Research Council for THB 150,000 ($4,600). The award is "not a lot of money in the US," Karoonuthaisiri said, "but it is a lot of money for Thais."

'Culture of R&D'

BIOTEC's microarray lab is the only one of its kind in Thailand and is unique in this part of Southeast Asia. With neighbors like Burma, Cambodia, Laos, Malaysia, and Vietnam, plus the prominence of Bangkok as a regional center for multinationals, it would seem that the lab would be busy with biotech partnerships, but, according to Karoonuthaisiri, that's not yet the case.

"We hoped that we could be a hub of biotech in Southeast Asia, but it's still a way to go to promote our biotechnology because we don't have a lot of resources," Karoonuthaisiri said.

"Biotechnology is not the kind of industry where you can work for a day and get a result; some drugs take 10 years or more to develop to be one competent drug that is making money.

"Money is the thing that hinders the process of moving forward because one single company doesn't have that much money [to invest] and if they do, it's easier to invest in a hotel and get a return faster," Karoonuthaisiri continued.

"To be able to see a long-term profit like investing in biotech is not a tradition here but I think it is getting there," she added. " but I hope that biotech will be able to have one or two cases of success stories and other investors will come in and say, 'This was successful, why can't we do this?' That is what we are trying to do here."

BIOTEC is trying to encourage more public-private partnerships. NSTDA is currently constructing a new incubator on its campus outside Bangkok where it hopes to house companies. The approach is roughly modeled on Singapore's Biopolis.

"The culture of R&D within a private company is not well established in Thailand," Karoonuthaisiri said. "Unlike the US, where a private company has its own R&D, in Thailand, due to lack of human resources and lack of infrastructure and equipment, NSTDA and BIOTEC have tried to encourage them to do R&D, but if they do not have the resources they can rent space here" and outsource research projects to BIOTEC, she said.

"We are trying to build a culture of investing in research," Karoonuthaisiri said. "Once that culture has become more successful, other people will do the same."

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