http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=58609

Researchers In Montreal And The US Create Model Of Key Immune-System Component

14 Dec 2006
systems biologyの手法を使って食細胞phagosomeの機能の研究に有用なシミュレーション用モデルを世界で初めて開発。
食細胞は結核、サルモネラ菌中毒、更に生物兵器に利用される病原菌といった感染性病原菌の破壊に関わる細胞小器官である。
proteomicsやgenomicsに基づく一般的なアプローチを使って、感染に関わる分子のプロセス理解を進めることができる。
ミバエの食細胞の細胞系分析により、食細胞の活動に関わる600以上のタンパク質を検出した。
次いで、これらのタンパク質の関係の詳細なマップを作成し、従来、知られていなかった食細胞の統制機能と免疫防衛の分子パスウェイと思われるものを明らかにすることができた。
食細胞は多くの組織で類似性が高いので、このような簡単な組織を研究することでこのプロセスが研究できたと研究者は言う。
従来の細胞生物学とproteomics、functional genomics更にcomputational analysisを結びつけてモデルを構築したが、これは感染性疾病の理解を深め、病原菌との闘いの新たな戦略作成に寄与するであろうという。
Researchers at Universite de Montreal, working with teams at Massachusetts General Hospital and Johns Hopkins University, have made a major breakthrough in understanding an essential aspect of the immune system. For the first time, using a systems biology approach, they have developed a model that facilitates the study of the function of the phagosome.
The phagosome is the organelle responsible for the destruction of infectious pathogens that cause such diseases as tuberculosis and salmonellosis, as well as pathogens that could be used in bioterrorism. The results of their study were published this week in the prestigious journal Nature.
Infectious diseases remain one of the main causes of death in the world, and the phenomenon of antibiotic resistant bacteria worsens the situation each year. Thanks to the model developed by teams led by Michel Desjardins of the Department of Pathology and Cellular Biology at Universite de Montreal, Drs Lynda Stuart and Alan Ezekowitz at the Massachusetts General Hospital, a Harvard Medical School teaching hospital, and Dr Joel Bader of the Biomedical Engineering Laboratory at Johns Hopkins University, it will now be possible to better understand the complex interactions that govern the functioning of the phagosome.
"We have taken a crucial step here," Prof. Desjardins explains. "We can now reach a better understanding of the molecular processes involved in infections by using a global approach based on proteomics and genomics. This approach will expedite development of therapies and the production of new vaccines. The major investments made in recent years in proteomics research in Québec and Canada have enabled us to pool our resources and apply promising new approaches like systems biology."
As Dr. Stuart explains, "Phagocytes are immune system cells that internalize, kill, and digest bacteria within an intracellular compartment called the phagosome, a major battleground in the host-pathogen conflict. Despite its important role in our normal immune defense, the organization and functioning of the phagosome are poorly understood."
By analyzing a cell line of phagocytes from the Drosophila fruit fly, a common biological model, the researchers identified more than 600 proteins that may be involved with the operation of the phagosome.
They then constructed a detailed map of the interactions among these proteins and were able to identify previously unknown regulators of phagocytosis and potential molecular pathways of immune defense.
"Phagocytosis is very similar in many organisms, so we are able to learn about this process by studying it in simpler organisms, such as Drosophila," Dr. Stuart continues.
"By combining classic cell biology with the newer approaches of proteomics, functional genomics and computational analysis, we have generated a model of that we believe will facilitate our understanding of infectious diseases and expedite the development of new strategies to fight pathogens."

"It is exciting to see that systems biology has the power to unravel how the phagosome works by revealing the intricately woven roles of all the molecules involved in killing infectious agents," says Joel Bader, Ph.D., Assistant Professor of Biomedical Engineering and a member of the High-Throughput Biology Center at Hopkins.