A globally unique 19F, 13C, 15N NMR system to enable frontier bioscience

我们使用一种名为核磁共振波谱(核磁共振)的技术来研究生物分子的结构，这些生物分子构成了细胞和生物体的复杂机械。它们的结构决定了它们如何工作和相互作用，并构成了人类在理解尖端生物科学方面相当大的努力的基础。我们计划购买世界上第一个TXO-HF核磁共振低温探头技术，并利用它在帕金森氏症等神经退行性疾病、设计新生物分子结构或生产抗病毒、抗生素和抗真菌化合物等领域取得突破性发现。我们还可以利用这些新的核磁共振数据来设计或重新调整药物的用途，使它们更有效，甚至可以观察当你的身体试图代谢下一代药物时，它们会发生什么。我们已经确定了这台仪器将从第一天起支持的3000万英镑的资助研究项目、国家合作和博士培训项目，我们正在与一系列国家网络合作，这些网络将使我们能够在核磁共振仪器的生命周期内大幅增加这一数字。新的探测器将使这项研究成为可能，因为核磁共振与医院中发现的全身核磁共振扫描仪具有相同的基本理念。然而，当研究生物科学中的分子时，很难获得足够的样本来用我们的核磁共振光谱仪检测，而核磁共振研究的“标准”原子核(质子)往往是如此丰富，以至于它给出了非常‘嘈杂’的光谱，有太多的信号，我们无法解释。解决这些问题的办法是使用核磁共振“冷冻探头”，它具有非常灵敏的探测能力，并经过优化，可以观察其他类型的原子核，这些原子核往往会发出更多的扩散信号。一些核磁共振系统已经开始使用碳和氮核，但让我们将要安装的TXO-HF系统特别强大的是，它还可以使用另一个原子核，氟，它是唯一强大的探测器，因为它在大多数自然系统中是罕见的。这意味着我们可以使用尖端的生物合成技术将氟引入我们研究的分子中，然后在没有质子核磁共振发现的所有背景噪音的情况下跟踪其行为，从而研究生物学中的一些非常困难的问题。使用这种新设备有许多更重要和更复杂的科学问题需要回答，为此，我们与许多合作大学、国家核磁共振网络项目和生物制药公司进行了合作。通过将所有这些不同的群体聚集在一起，我们确保了我们最大限度地增加了人数，并拥有可以应用于我们面临的科学挑战的广泛专业知识。随着大学如何合作的全国性图景的演变，共享(昂贵！)像这样独特和复杂的设备变得越来越重要。因此，我们寻求用这台设备做的一部分是将其作为榜样，以鼓励我们熟练的研究技术专业人员运行这些仪器的合作和培训，并激励学生，他们自己将成为未来的生物科学研究人员和核磁共振光谱学家。为了做到这一点，我们与一个支持这一想法的敬业团队进行了合作，并希望通过这个团队使设备更具影响力和可持续性。

We use a technique called Nuclear Magnetic Resonance spectroscopy (NMR) to study the structure of biomolecules that form the intricate machinery of cells and organisms. Their structure determines how they work and interact with each other and forms the basis of considerable human effort in understanding cutting edge bioscience. We are proposing to purchase the world's first TXO-HF NMR cryogenic probe technology and use it to make ground-breaking discoveries in areas such as neurodegenerative conditions like Parkinson's disease, design the structure of new biomolecules, or the production of antiviral, antibiotic and antifungal compounds. We can also use this new NMR data to design or repurpose drugs to make them more potent and even look at what happens to next generation drugs when your body tries to metabolise them. We have already identified >£30m of funded research programs, national collaborations and doctoral training programs that this instrument will underpin from day one, and we are working with a range of national networks who will allow us to increase this substantially over the lifetime of the NMR instrument. The new probe will enable this research because NMR shares the same basic ideas as the whole-body MRI scanners that are found in hospitals. However when studying molecules in bioscience, it is difficult to get enough sample to detect with our NMR spectrometer and the 'standard' atomic nucleus that MRI studies (the proton), tends to be so abundant that it gives very 'noisy' spectra with too many signals for us to be able to interpret. The solution to these problems is to use an NMR 'cryoprobe' that has very sensitive detection and is optimised to look at other types of atomic nuclei that tend to give more spread-out signals. Some NMR systems have started to use carbon and nitrogen nuclei, but what makes this TXO-HF system we are going to install especially powerful is that it can also use a further nucleus, fluorine, that is uniquely powerful as a probe because it is rare in most natural systems. This means we can use cutting-edge biosynthetic techniques to introduce fluorine into the molecules we study and then follow it's behaviour without all of the background noise that is found with proton-based NMR and thus study some very difficult problems in biology. There are many more important and complex scientific questions to answer with this new equipment and to do this we have teamed up with many partner universities, national NMR network programs and biopharmaceutical companies. By bringing all of these different groups together we are ensuring we maximise the number of people and have a broad expertise that can be applied to the scientific challenges we face. As the national picture of how universities work together evolves, sharing (expensive!) unique and sophisticated equipment like this becomes ever more important. Therefore part of what we are seeking to do with this equipment is use it as an exemplar to encourage collaboration and training for our skilled research technical professionals who run these instruments, as well as to inspire the students who themselves will go on to be the bioscience researchers and NMR spectroscopists of the future. To do this we have engaged with a dedicated team who champion this idea and through which we hope to make the equipment even more impactful and sustainable.