Modelling the Gene Regulatory Network underlying Lineage Commitment in Human Mesenchymal Stem Cells (LINCONET)

人类间充质干细胞谱系定型的基因调控网络建模 (LINCONET)

• 批准号: BB/I004556/1
• 负责人: Francesco Falciani
• 金额: $ 34.48万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FI004556%2F1
• 关键词: Modelling; Gene; Regulatory; Network; underlying

With the aging of the world population, degenerative diseases such as osteoporosis and arthritis will have an increasing impact on health and quality of life. Restoration of damaged bone and cartilage by stimulating human mesenchymal stem cells (HMSCs) to differentiate into bone- or cartilage-synthesizing cells provides a novel and attractive therapeutic opportunity with profound implications in biomedicine. This requires a thorough understanding of the normal biological processes underlying cell differentiation and the disease-induced tissue degeneration. Given the multi-potent character of stem cells, and the complexity of the cross-talk between signalling pathways that determine lineage commitment and disease progression, an integrated approach that uses advanced computational techniques (a systems biology approach) is essential. This project aims to develop a framework to understand tissue regeneration. To this end, we will unravel and mechanistically model the genetic network underlying normal tissue regeneration processes. An integral part of our strategy is to experimentally validate hypotheses generated by computational models by using tightly integrated cycles of computational modelling and experimental verification at the cellular and organism level.

随着世界人口的老龄化，骨质疏松症和关节炎等退行性疾病将对健康和生活质量产生越来越大的影响。通过刺激人间充质干细胞（HMSC）分化为骨或软骨合成细胞来修复受损的骨和软骨提供了一种新颖且有吸引力的治疗机会，在生物医学中具有深远的意义。这需要对细胞分化和疾病诱导的组织变性的正常生物学过程有透彻的理解。鉴于干细胞的多能性，以及决定谱系定型和疾病进展的信号通路之间的相互作用的复杂性，使用先进的计算技术（系统生物学方法）的综合方法是必不可少的。该项目旨在开发一个框架来理解组织再生。为此，我们将解开和机械模型的遗传网络的基础正常组织再生过程。我们的策略的一个组成部分是通过使用紧密集成的计算建模和实验验证在细胞和生物体水平的周期，实验验证由计算模型产生的假设。

项目成果

Inference of Low and High-Grade Glioma Gene Regulatory Networks Delineates the Role of Rnd3 in Establishing Multiple Hallmarks of Cancer.

• DOI: 10.1371/journal.pgen.1005325
• 发表时间: 2015-07
• 期刊: PLoS genetics
• 影响因子: 4.5
• 作者: Clarke K;Daubon T;Turan N;Soulet F;Mohd Zahari M;Ryan KR;Durant S;He S;Herbert J;Ankers J;Heath JK;Bjerkvig R;Bicknell R;Hotchin NA;Bikfalvi A;Falciani F
• 通讯作者: Falciani F

Stromal transcriptional profiles reveal hierarchies of anatomical site, serum response and disease and identify disease specific pathways.

• DOI: 10.1371/journal.pone.0120917
• 发表时间: 2015
• 期刊: PloS one
• 影响因子: 3.7
• 作者: Filer A;Antczak P;Parsonage GN;Legault HM;O'Toole M;Pearson MJ;Thomas AM;Scheel-Toellner D;Raza K;Buckley CD;Falciani F
• 通讯作者: Falciani F