Scientists at the Industrial Technology Research Institute in Hsin-chu, Taiwan say they have jumped one to two years ahead of “everyone else” in assembling the components of the human liver proteome, using a multidimensional liquid chromatography front-end technique that they say allowed them to identify 4,000 human liver proteins in just a few months.
Chungcheng Liu, the former Genentech scientist leading this project, presented ITRI’s preliminary data — which included 5,000 mouse liver proteins identified over seven to eight months as well as the 4,000 human liver proteins found in cooperation with a local hospital that provided tissue from transplantation work — to a press corps in Taipei earlier this month.
This presentation follows on the heels of a talk by Fuchu He, the Beijing–based leader of the HUPO Liver Proteome Project, at the HUPO Congress in October describing the identification of 2,395 human fetal liver proteins. The HLPP has only re-cently entered its pilot phase, which will wrap up in 2005 (see PM 10-31-03). “The HUPO proteome project is still organizing” while the ITRI project is jumping ahead, Liu said.
Liu’s initiative, involving about 30 scientists at the Biomedical Engineering Center at ITRI — of which Liu is deputy general director — is entirely separate from the HLPP, as well as from core facility proteomics infrastructure development projects such as the one set up at Academia Sinica in Taipei (see PM 8-15-03), Liu said. That doesn’t mean, however, that cooperation among the efforts is not in the cards: Liu added that HUPO president Sam Hanash is “interested” in his data, and that some of the data will likely be made available to the HLPP — if Liu’s Taiwanese governmental sponsors, who would control any resulting intellectual property from the project, approve. “The [sponsoring] Ministry of Economic Affairs is anticipating some return for its investment,” Liu said.
In fact, the Taipei presentation was a standard move to impress the group’s government sponsors at the Ministry of Economic Affairs into continuing to fund the project. The project, in its second year, receives about $3 million per year from the ministry with a projected three- to four-year commitment, but projects are reviewed on a yearly basis, so “the pressure is on” to keep the Ministry interested even before data is published, Liu said. The group is working on a journal manuscript now, but is taking its time to make sure the data is worthy of a big publication. “We’d like to make the publication in a major journal like Science or Nature Biotech,” he said.
Liu’s methods were inspired by a paper that F. Hoffman–La Roche published two years ago showing a yield of 300 mouse liver proteins identified from a 2D gel that contained 6,000 spots. “I found that [ratio] unacceptable,” Liu said. Instead, he turned to liquid chromatography, running relatively large samples — on the order of 1 g — through three or four layers of columns in order to get as clear a signal as possible. “If you want to purify and identify proteins at the sensitivity level of 1 µg, then you obviously need to start with 1 g of protein, otherwise you would never see it. It’s a simple principle that people in biochemistry know very well,” he said.
After fractionation, Liu’s group fed the samples into its Applied Biosystems Q-STAR or its 4700 MALDI TOF/TOF for identification — although Liu commented that the 4700 still needed some “fine-tuning.”
Liu’s work began in response to a recommendation two years ago from a technology advisory committee that the Taiwanese government peg proteomics as an “important direction” for biotechnology. The government has identified biotechnology as one of two “stars” that it hopes will bring further business development to the island, and the MEA hopes that Liu’s project will help it achieve this goal.
“ They’d like to see some impact on the business community here,” he said. “Obviously the best way is some entrepreneur here finds a way to use this information to start a biotech company. … The other alternative is to combine these results with a drug research effort, and also this could be achieved by some major biopharma from the US or Europe recognizing this important resource and deciding to have a collaboration with us and maybe fund or establish a research lab in Taiwan. We know we can’t do this alone.”
Liu is no stranger to biotech companies: He spent 10 years at Genentech and another seven years at Genencor before returning to Taiwan four years ago to lead the ITRI. “Some people here think I’m too Americanized,” he said. “But I think I understand some of why certain companies can do things well and some can’t.”
Along with his proteomics work, Liu also does research in microarrays — he claims that ITRI has the most efficient array technology in the world for making spotted arrays — and also works with DNA sequencing, bioinformatics, and stem cell technology, among other projects.