分子成像解码人体组织在健康和疾病

简介: 以便更快更有效地将新药带给患者, 澳门第一赌城在线娱乐必须提高对澳门第一赌城在线娱乐想要治疗的疾病的理解. Using advanced molecular imaging – propelled most recently by mass spectrometry – our scientists are able to probe and analyse 组织 samples in a depth and detail that was previously impossible. 通过利用人工智能和机器学习的强大力量, the full molecular complexity is finally becoming decipherable and is already revealing insights that have the potential to fundamentally transform future drug discovery and development.

对疾病的分子理解如何帮助评估药物安全性

Integral to modern drug discovery is the ability to understand – in as much detail as possible – the effects of our compounds on human 组织s at a cellular level. 换句话说，就是澳门第一赌城在线娱乐的候选药物在病人体内的作用. 几十年来,, 科学家们使用了传统的组织学和组织病理学技术, 染色组织样本，寻找特定的细胞形态, 显微镜载玻片上的标记和信号. 找出药物分子在体内的去向(生物分布), 以前唯一可用的选择是放射自显影, an expensive and laborious radio-labelled approach with limited ability to only image distribution of a single target.

现在, a suite of innovative technologies which make up our advanced molecular imaging capabilities have enabled a quantum leap in our ability to understand disease processes and evaluate drug efficacy and safety. 这些技术使澳门第一赌城在线娱乐能够探测每一个组织样本——无论是来自病人的活组织检查, 动物模型或先进的细胞培养-前所未有的深度. Combining these remarkable powers of detection with the incredible analysis and interpretation capabilities of artificial intelligence (AI) and machine learning means we can explore uncharted territory with open minds in our search for the unknown and unexpected.

用质谱成像导航人体分子的复杂性

在这个领域，质谱成像(MSI)的进步已经成为真正的游戏规则改变者. We are now able to simultaneously measure the individual masses of molecules using a mass spectrometer, 可视化它们的空间分布，无论是多肽, 蛋白质, 脂质, 内源性代谢物或药物分子-在组织的微环境内, providing vital clues to their inter-relationships and allowing us to better assess the safety and efficacy of compounds.

质谱法本身当然并不新鲜. 用于许多研究和开发领域, 它依赖于电离过程:将组织样本转化为气体形式. What is special about MSI is that the 组织 sample is not homogenised (mixed-up) prior to ionisation. 而不是, 它被快速冷冻，并直接从其完整的表面电离, 所以每个分子的初始位置是已知的. The whole sample is scanned a few microns at a time with each discrete location analysed forming one pixel in the images we ultimately generate. 这提供了丰富的数字信息.

创建“谷歌地球”视图

Today’s advanced molecular imaging techniques – and MSI in particular – mean we can now create the most detailed molecular maps ever. Much like Google Earth software enables a satellite view of the planet down to 3D views of individual streets and buildings, 澳门第一赌城在线娱乐的新成像功能允许澳门第一赌城在线娱乐放大和缩小从微观到宏观的水平和回来. Our mass spectrometers even enable us to do the equivalent of looking through the window of a house to see where the sofa is.

澳门第一赌城在线娱乐检测到的每个分子都有自己的图谱, 由成千上万张不同角度的图片拼凑而成. 澳门第一赌城在线娱乐可以“看到”药物分子, biomarkers and the 组织 microenvironment simultaneously and examine the picture from the genomic and molecular viewpoint up to the cellular, 组织, 器官和患者水平. 大量的数据集是从健康的, diseased and drug-treated 组织 samples which can then be mined by AI and machine learning techniques to spot patterns, 连接和关系的复杂性远远超过以往任何时候, 将信息转化为见解，见解转化为知识. 

有了这些知识，澳门第一赌城在线娱乐将更有能力设计出安全有效的药物, 开发最佳给药方法, 制定适当的剂量并监测疾病进展. 使用这些方法，澳门第一赌城在线娱乐已经发现了新的见解，例如:

• The first mechanistic description of how metabolites generated by the gut microbiome might play a role in neurological conditions like Parkinson’s¹
• 肺转移中营养物质感知与利用的机制² 结肠直肠癌³
• 一种新的三维肺腺癌模型，可以模拟肺腺癌 在活的有机体内 组织和肿瘤微环境⁴
• Preclinical imaging to explore the penetration of oncology drug candidates across the blood brain barrier and their impact on brain tumour growth⁵
• High-resolution 3D visualisation of nanomedicine distribution providing valuable insights into the influence of the tumour vasculature and microenvironment on nanomedicine localisation⁶

英国癌症研究中心的“大挑战”

澳门在线赌城娱乐是一个创新的五年多中心项目的一部分, multidisciplinary collaboration that aims to plot the most detailed map ever seen of the molecular landscape of malignant tumours.

英国癌症研究中心(CRUK), this ‘Grand Challenge’ is led by 约瑟芬·邦奇教授 from the National Physics Laboratory and the consortium includes leading scientists from the Francis Crick Institute, 格拉斯哥的比特森研究所, 剑桥大学和许多其他大学.

The team’s database will be made available to researchers worldwide and its approaches used to create standardised, 部署最新技术的最佳实践指南.

合作 with academia is key for us to push the boundaries of science and drive disease discovery and understanding to help us create the next generation of therapeutics.

参考文献

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3. 氨基酸转运体SLC7A5是kras突变型结直肠癌有效生长所必需的. Nat Genet 53, 16-26 (2021). http://doi.org/10.1038/s41588-020-00753-3
4.  Characterization of an Aggregated Three-Dimensional Cell Culture Model by Multimodal Mass Spectrometry Imaging - 2020 Sep 15;92(18):12538-12547. doi: 10.1021 / acs.analchem.0c02389. 
5. Preclinical comparison of the blood brain barrier (BBB) permeability of osimertinib with other EGFR TKIs - 2020 Oct 7;clincanres.1871.2019. doi: 10.1158/1078-0432.ccr - 19 - 1871. 
6. 纳米药物在肿瘤中分布的高分辨率三维可视化[j]; 2020;1 (2):880-897. doi: 10.7150 / thno.37178.