News Release

Gene's novel role may provide key to treating liver and neurodegenerative diseases

'FAIM' gene research conducted by Singapore scientists

Peer-Reviewed Publication

Agency for Science, Technology and Research (A*STAR), Singapore

Scientists at Singapore's Bioprocessing Technology Institute (BTI) have made a novel discovery about how the gene, "Fas-apoptosis inhibitory molecule" (FAIM), protects both immune and liver cells from apoptosis, or programmed cell death.

Their research is published in the current journal Cell Death and Differentiation.

The scientists, Jianxin Huo, Ph.D., and Shengli Xu, Ph.D., also discovered that this process may possibly be manipulated for clinical application and proposed the first-to-be-published in-animal model to study the role of FAIM in detail.

FAIM triggers a mechanism that ultimately impedes an important pathway to apoptosis, which is mediated by a key protein called Fas. Using their mouse model, the scientists elucidated part of the sequence of molecular events that regulates Fas-mediated apoptosis.

They found that FAIM functioned as a key switch in the Fas cell death circuit, which could be turned up or down to prolong or decrease cell survival.

Therefore, in principle, this gene could make a good target for drug intervention in either liver cirrhosis in which the target is to prolong cell survival, or in cancer in which the goal is to induce tumour cell death.

BTI Scientific Director Lam Kong Peng, Ph.D., who heads the immunology group that conducted the research, said, "We had earlier identified FAIM to be valuable in increasing the yield of biologics, and that had been one of the main focuses of BTI's research until now. We were extremely pleased to be able to establish that FAIM's function is preserved across both liver and immune cells, as this underscores its critical role in regulating cell death in disease."

The immunology team at BTI, one of the research institutes sponsored by Singapore's A*STAR (Agency for Science, Technology and Research), aims to further characterize the role of FAIM in liver cancer and other debilitating diseases.

According to Drs. Huo and Xu, there is also significant existing evidence that FAIM prevents neuron death and promotes neural outgrowth.

They hypothesize that FAIM might play a role in neuron protection, making it a potential therapeutic target for neurodegenerative diseases such as Alzheimer's and Parkinson's. Eventually, the Singapore scientists hope to conduct drug screens on FAIM to determine how it can be used to prolong or delay cell survival, and provide solutions to a wide variety of human diseases.

Drs. Huo and Xu's interest in FAIM was sparked by the work of their colleagues in BTI's animal cell technology group, which since 2007 has been using FAIM to enhance the longevity of biologics-producing cells to increase their yield in bioreactors, which are vessels in which organisms are cultured, and biochemically active substances derived from them.

Biologics are medicinal products such as vaccines, allergenics, tissues and recombinant proteins that can be extracted from natural sources (human, animal, or microorganism) and produced by biotechnology methods.

Curious about FAIM's role in immune cells, particularly its increased expression in activated B cells, key effectors of the human immune system responsible for fighting viruses and other pathogens that invade the body, the two scientists began developing the first in vivo knockout mouse model to closely examine FAIM's role in preventing programmed cell death.

BTI Executive Director Miranda Yap, Ph.D., said, "The Immunology Group's venturing beyond the traditional boundaries of applied science has paid off with their discovery of a second role for FAIM in the seemingly unrelated field of immunology. Their work is indeed a fine example of how our scientists are constantly pushing the envelope to keep at the forefront of biomedical research."

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The Cell Death and Differentiation paper, "Genetic deletion of faim reveals its role in modulating c-FLIP expression during CD95-mediated apoptosis of lymphocytes and hepatocytes," is authored by: J. Huo, S. Xu, K. Guo, Q. Zeng and K-P Lam.

AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH

For more information:
Ms Adela Foo
Senior Officer, Corporate Communications
DID: (+65) 6826 6218 | Fax: (+65) 6478 9593
Email: adela_foo@a-star.edu.sg

BIOPROCESSING TECHNOLOGY INSTITUTE: (www.bti.a-star.edu.sg)

Bioprocessing Technology Institute (BTI) is a member of the Agency for Science, Technology and Research (A*STAR). Established in 1990 as the Bioprocessing Technology Unit, it was renamed the Bioprocessing Technology Institute (BTI) in 2003. The research institute's mission is to develop manpower capabilities and establish cutting-edge technologies relevant to the bioprocessing community. Some of the key research areas include expression engineering, animal cell technology, stem cell research, microbial fermentation, downstream purification and analytics.

AGENCY FOR SCIENCE, TECHNOLOGY AND RESEARCH: (www.a-star.edu.sg)

The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based Singapore. A*STAR actively nurtures public sector research and development in Biomedical Sciences, and Physical Sciences and Engineering, and supports Singapore's key economic clusters by providing intellectual, human and industrial capital to our partners in industry and the healthcare sector. A*STAR oversees 23 research institutes, consortia and centres located in Biopolis and Fusionopolis, and the area in their vicinity, and supports extramural research with the universities, hospital research centres, and other local and international


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