2006-09-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/680351摘要：系統生物學是在生物學上一個新興的領域，它著重於以系統的觀點來了解生物系統的運作。由於高通量藥物合成、蛋白質體、微陣列及生物資訊技術的發展，使得系統生物學的研究愈發可行了。生物轉變的整體研究將能加快闡明生化路徑及疾病治療的速度。除此之外，系統生物學也著重於描述和了解複雜的生物系統如何運作以及發展預測人類疾病的模式。在本計畫中將會利用系統生物學的研究方法來探討藥物對癌細胞的作用模式。 雖然疾病生物學很複雜，而藥物開發則必需倚靠生物反應，但是"基因到藥物"的希望之路已經是一觸即發，即將成功。對於改善現行的癌症治療，如何使藥物能專一地作用在癌細胞上仍然是一個主要的挑戰。因為RGD motif與很多重要的生化反應機制息息相關，所以找出最有效含RGD胜&#32957;的藥物將是非常重要的。 本計畫主要的目標是要整合化學、生物學和計算學，並使用系統生物學研究法來研究在RGD胜&#32957;誘導下乳癌細胞進行細胞凋亡的作用機制；進一步地利用系統生物學研究法來開發新的藥物以治療癌症。 本整合型研究計畫有幾個特定的目標，如以下所述： 1.以RGD胜&#32957;為基礎，設計並合成有潛力的藥物；<br> Abstract: Systems biology is a new field in biology that focuses on an understanding of functional activity from a systems-wide perspective. Recently, with the advent of high-throughput drug synthesis, proteomics, microarray and bioinformatics technologies, the study of systems biology has become possible. The holistic study of biological transformations will enable more rapid advances in elucidating biochemical pathways and disease therapies. The hope of the rapid translation of 'genes to drugs' has foundered on the reality that disease biology is complex, and that drug development must be driven by insights into biological responses. Targeting drugs to tumor cells is a central challenge for improving existing cancer therapies. Since the RGD motif is involved in many important biochemistry mechanisms, it is of great interest to conduct the most effective RGD-containing peptide drugs. RGD-containing peptides have been demonstrated to strongly inhibit the adhesion, migration, invasion of tumor cells and tumor growth of human breast cancer cells. The major objectives of this proposal are to integrate chemistry, biology and computation to investigate the molecular mechanism of apoptosis in RGD-peptide-induced MCF-7 breast cancer cells using systems-biology approach; furthermore, to discover novel drugs for cancer therapy. Specific aims: 1.To design and synthesize potential drugs based on RGD peptides; to analyze the activity of anti-cancer drugs. 2.Identification of therapeutic biomarkers for the treatment of breast cancer by integrating proteomics and genomics expression profiles. 3.To develop high throughput protein array platforms based on the identified proteins and explore apoptosis pathways. 4.To development in silico modeling procedures for biological networks; then reconstruct and simulate the apoptosis network of RGD mimetic compounds acting on cancer cells. 5.To verify the biological network and pathways using biological experiments such as Q-PCR, RNAi and protein array. 6.To discover the molecular mechanism for novel compounds acting on cancer cells.系統生物學基因網路細胞凋亡Systems biologyGene networkApoptosis