Multi-modal Discovery of Mechanistic Drivers of Pulmonary Fibrosis
肺纤维化机制驱动因素的多模式发现
基本信息
- 批准号:MR/W031469/1
- 负责人:
- 金额:$ 129.48万
- 依托单位:
- 依托单位国家:英国
- 项目类别:Research Grant
- 财政年份:2022
- 资助国家:英国
- 起止时间:2022 至 无数据
- 项目状态:未结题
- 来源:
- 关键词:
项目摘要
Idiopathic pulmonary fibrosis (IPF) is a progressive lung condition characterised by scarring (fibrosis) of the lungs. This scarring deforms the lungs and reduces the ability of the lungs to take in oxygen, which causes a person to feel breathless and cough. It is not clear why some people develop IPF, but people with IPF often progress quickly to death and there is no cure. Each year 6000 people in the UK die of IPF, more than deaths from most cancers, and more than ovarian, cervical and thyroid cancers combined. This makes IPF an important disease to research. It is currently thought that genetic changes in the cells that line the lung (epithelial cells) make them susceptible to injury and scar formation, although, how these genetic changes promote scarring remains unknown. The main feature of lung scarring is that the lungs become small and stiff due to the abnormally high activity of cells that make scar tissue. It is known that genetic changes in cells that line the small airways lead to the production of increased mucous which we believe makes the cells that line the airsacs (alveoli) stiffer and unable to respond to injury in a normal way. When the lung is damaged the injured cells die and need to be replaced by new cells that originated from a special type of airsac cell called (an alveolar type 2 cell) however in scarred lung these cells begin to change to the lining cells but get stuck in a transitional state that is neither a specialised nor lining cell which we believe is related to the build up of mucous and increased stiffness of the lung. Research has shown that when lung cells grow in stiff surroundings, such as that within a scarred lung, they become even more active and produce more scar tissue. However, how mechanical forces affect cells with genetic changes found in IPF, or how the genetic changes affect the signals the that epithelial cells send and the fate that injured epithelial cells undergo remains unknown. Importantly it is possible to change the cell fate through adapting the mechanical forces within the lung is not currently known.This programme of work will use a number of distinct but complementary scientific techniques including genetics, cell and molecular biology, bioinformatics, bioengineering and biophysics to understand these interactions and determine whether we can alter the fate of lung cells and reprogram them by changing the mechanical environment they exist.This study will bring world leading scientist from a wide range of disciplines to try and find new insights to alleviate the suffering from this devastating disease. The programme will focus on a key cellular process which could link the known genetic, molecular, cellular and mechanical faults that are associated with IPF. The aim of this project is to understand 1) whether a process called cellular extrusion by which abnormal, or excess cells are squeezed out of cell layers occurs in the small airsacs of the lung 2) understand how this process is altered in scarred lung and whether it can be changed to promote lung healing 3) understand the environment in which the cells live can affect how they behave 4) use artificial intelligence and deep learning algorithms to both learn from and inform our experiment in aims 1 to 3.
特发性肺纤维化(IPF)是一种以肺瘢痕形成(纤维化)为特征的进行性肺部疾病。这种疤痕使肺部变形,降低了肺部吸入氧气的能力,这会导致一个人感到呼吸困难和咳嗽。目前尚不清楚为什么有些人会患上IPF,但IPF患者通常会迅速进展至死亡,并且无法治愈。英国每年有6000人死于IPF,超过大多数癌症的死亡人数,超过卵巢癌、宫颈癌和甲状腺癌的总和。这使得IPF成为研究的重要疾病。目前认为,肺细胞(上皮细胞)的遗传变化使它们容易受到损伤和瘢痕形成的影响,尽管这些遗传变化如何促进瘢痕形成仍然未知。肺瘢痕形成的主要特征是,由于形成瘢痕组织的细胞的异常高活性,肺变得小而僵硬。众所周知,排列在小气道上的细胞的遗传变化会导致粘液的产生增加,我们认为这会使排列在气囊(肺泡)上的细胞变硬,无法以正常的方式对损伤做出反应。当肺受损时,受损细胞死亡,需要由源自一种特殊类型的气囊细胞(肺泡2型细胞)的新细胞取代,然而在疤痕肺中,这些细胞开始改变为衬里细胞,但陷入过渡状态,既不是专门的也不是衬里细胞,我们认为这与粘液的积累和肺硬度增加有关。研究表明,当肺细胞在僵硬的环境中生长时,例如在有疤痕的肺内,它们变得更加活跃,并产生更多的疤痕组织。然而,机械力如何影响IPF中发现的具有遗传变化的细胞,或者遗传变化如何影响上皮细胞发送的信号以及受损上皮细胞经历的命运仍然未知。重要的是,通过适应肺内的机械力来改变细胞命运的可能性目前尚不清楚。这项工作计划将使用一些不同但互补的科学技术,包括遗传学,细胞和分子生物学,生物信息学,生物工程和生物物理学来理解这些相互作用,并确定我们是否可以改变肺细胞的命运,并通过改变机械环境来重新编程它们。他们存在。这项研究将带来世界领先的科学家从广泛的学科,试图找到新的见解,以减轻痛苦,从这种毁灭性的疾病。该计划将重点关注一个关键的细胞过程,该过程可能与IPF相关的已知遗传,分子,细胞和机械故障有关。这个项目的目的是了解1)是否一个过程称为细胞挤出,或多余的细胞被挤出细胞层发生在肺的小气囊2)了解这个过程是如何改变的疤痕肺和它是否可以改变,以促进肺愈合3)了解细胞生活的环境可以影响他们的行为4)使用人工智能和深度学习算法,从目标1至3的实验中学习并为之提供信息。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Beyond epithelial damage: vascular and endothelial contributions to idiopathic pulmonary fibrosis.
- DOI:10.1172/jci172058
- 发表时间:2023-09-15
- 期刊:
- 影响因子:15.9
- 作者:May, James;Mitchell, Jane A.;Jenkins, R. Gisli
- 通讯作者:Jenkins, R. Gisli
B7-H3 Associates with IMPDH2 and Regulates Cancer Cell Survival.
B7-H3与IMPDH2相关并调节癌细胞的存活。
- DOI:10.3390/cancers15133530
- 发表时间:2023-07-07
- 期刊:
- 影响因子:5.2
- 作者:
- 通讯作者:
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Gisli Jenkins其他文献
A roadmap to precision treatments for familial pulmonary fibrosis
家族性肺纤维化精准治疗路线图
- DOI:
10.1016/j.ebiom.2024.105135 - 发表时间:
2024-06-01 - 期刊:
- 影响因子:10.800
- 作者:
Killian Hurley;Mari Ozaki;Quentin Philippot;Liam Galvin;David Crosby;Mary Kirwan;Deborah R. Gill;Konstantinos-Dionysios Alysandratos;Gisli Jenkins;Matthias Griese;Nadia Nathan;Raphael Borie;Killian Hurley;Deborah Snijders;Nicolaus Schwerk;Nico Lachmann;Matthias Griese;Daniel O'Toole;Raphael Borie - 通讯作者:
Raphael Borie
REMOTE-ILD study: Description of the protocol for a multicentre, 12-month randomised controlled trial to assess the clinical and cost-effectiveness of remote monitoring of spirometry and pulse oximetry in patients with interstitial lung disease
REMOTE-ILD 研究:描述一项多中心、12 个月随机对照试验的方案,以评估间质性肺病患者肺活量测定和脉搏血氧测定远程监测的临床和成本效益
- DOI:
10.1136/bmjresp-2023-002067 - 发表时间:
2024 - 期刊:
- 影响因子:4.1
- 作者:
Sarah Barth;Colin Edwards;R. Borton;D. Beever;Wendy Adams;Gisli Jenkins;Elena Pizzo;Iain Stewart;Melissa Wickremasinghe - 通讯作者:
Melissa Wickremasinghe
Adaptive multi-interventional trial platform to improve patient care for fibrotic interstitial lung diseases.
自适应多介入试验平台,可改善纤维化间质性肺疾病的患者护理。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:10
- 作者:
Letícia Kawano;Tejaswini Kulkarni;Christopher J Ryerson;Pilar Rivera;B. Baldi;Nazia Chaudhuri;M. Funke;A. Hoffmann;Kerri A Johannson;Y. Khor;Sydney B Montesi;L. Piccari;Helmut Prosch;M. Molina;Jacobo Sellares Torres;Iazsmin Bauer;Sujeet Rajan;Joseph Jacob;Duncan Richards;Lisa G Spencer;B. Wendelberger;Tom Jensen;Melanie Quintana;M. Kreuter;Anthony C Gordon;Fernando J Martinez;Naftali Kaminski;Victoria Cornelius;Roger Lewis;Wendy Adams;Gisli Jenkins - 通讯作者:
Gisli Jenkins
Commonly prescribed medications and risk of pneumonia and all-cause mortality in people with idiopathic pulmonary fibrosis: a UK population-based cohort study
- DOI:
10.1186/s41479-024-00155-7 - 发表时间:
2025-01-25 - 期刊:
- 影响因子:6.200
- 作者:
Ann D. Morgan;Georgie M. Massen;Hannah R. Whittaker;Iain Stewart;Gisli Jenkins;Peter M. George;Jennifer K. Quint - 通讯作者:
Jennifer K. Quint
Gisli Jenkins的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Gisli Jenkins', 18)}}的其他基金
The UK Interstitial Lung Disease Long-COVID19 study (UKILD-Long COVID): understanding the burden of Interstitial Lung Disease in Long COVID.
英国间质性肺病长-COVID19研究(UKILD-Long COVID):了解长-COVID中间质性肺病的负担。
- 批准号:
MR/W006111/1 - 财政年份:2021
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
MICA - DEfining MechanIsms Shared across mulTI-organ FIbrosis to prevent the development of long-term multi-morbidity DEMISTIFI-Multi Morbidity
MICA - 多器官纤维化共享的定义机制,以防止长期多重发病的发展 DEMISTIFI-Multi Morbidity
- 批准号:
MR/W014491/1 - 财政年份:2021
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
MICA: Defining Endotypes of Pulmonary Fibrosis by Understanding the Functional Consequences of Known, and Novel, Genetic Associations with Disease
MICA:通过了解已知和新的与疾病的遗传关联的功能后果来定义肺纤维化的内型
- 批准号:
MR/V00235X/1 - 财政年份:2021
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
DEMISTIFI Multi Morbidity: DEfining MechanIsms Shared across mulTI-organ FIbrotic disease to prevent the development of long term multi-morbidity
DEMISTIFI 多重发病率:确定多器官纤维化疾病共享的机制,以预防长期多重发病率的发展
- 批准号:
MR/V005324/1 - 财政年份:2020
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
Refining models of fibrotic lung disease
细化纤维化肺疾病模型
- 批准号:
G1100564/1 - 财政年份:2011
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
The evaluation of the avb6 integrin as a biomarkers and therapeutic target for idiopathic pulmonary fibrosis
avb6整合素作为特发性肺纤维化生物标志物和治疗靶点的评估
- 批准号:
G0901226/1 - 财政年份:2010
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
相似国自然基金
基于异构医学影像数据的深度挖掘技术及中枢神经系统重大疾病的精准预测
- 批准号:61672236
- 批准年份:2016
- 资助金额:64.0 万元
- 项目类别:面上项目
相似海外基金
Flexible fMRI-Compatible Neural Probes with Organic Semiconductor based Multi-modal Sensors for Closed Loop Neuromodulation
灵活的 fMRI 兼容神经探针,带有基于有机半导体的多模态传感器,用于闭环神经调节
- 批准号:
2336525 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Standard Grant
Collaborative Research: NCS-FR: Individual variability in auditory learning characterized using multi-scale and multi-modal physiology and neuromodulation
合作研究:NCS-FR:利用多尺度、多模式生理学和神经调节表征听觉学习的个体差异
- 批准号:
2409652 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Standard Grant
Imaging for Multi-scale Multi-modal and Multi-disciplinary Analysis for EnGineering and Environmental Sustainability (IM3AGES)
工程和环境可持续性多尺度、多模式和多学科分析成像 (IM3AGES)
- 批准号:
EP/Z531133/1 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
MUSE: Multi-Modal Software Evolution
MUSE:多模式软件演进
- 批准号:
EP/W015927/2 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
High speed multi modal in-situ Transmission Electron Microscopy platform
高速多模态原位透射电子显微镜平台
- 批准号:
LE240100060 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Linkage Infrastructure, Equipment and Facilities
Multi-scale, multi-modal X-ray imaging using speckle
使用散斑的多尺度、多模态 X 射线成像
- 批准号:
DE220101402 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Discovery Early Career Researcher Award
Multi-modal electron microscopy of 3D racetrack memory
3D 赛道记忆的多模态电子显微镜
- 批准号:
EP/X025632/1 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Research Grant
NSF-SNSF: Rapid Beamforming for Massive MIMO using Machine Learning on RF-only and Multi-modal Sensor Data
NSF-SNSF:在纯射频和多模态传感器数据上使用机器学习实现大规模 MIMO 的快速波束成形
- 批准号:
2401047 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Standard Grant
FDG-PET in combination with proton (1H) and sodium (23Na) MRI: a di-modal metabolic imaging approach
FDG-PET 结合质子 (1H) 和钠 (23Na) MRI:双模态代谢成像方法
- 批准号:
24K15805 - 财政年份:2024
- 资助金额:
$ 129.48万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Enhancing STEM Success: A Multi-modal Investigating of Spatial Reasoning and Training in Undergraduate Education
促进 STEM 成功:本科教育空间推理和培训的多模式研究
- 批准号:
2300785 - 财政年份:2023
- 资助金额:
$ 129.48万 - 项目类别:
Continuing Grant