Support for increased capacity to facilitate enhanced stable isotope resolved investigations of human metabolism in the biosciences'

支持提高能力，促进生物科学中人类代谢的稳定同位素解析研究

• 批准号: BB/T017821/1
• 负责人: Daniel Tennant
• 金额: $ 23.26万
• 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: 2020
• 资助国家: 英国
• 起止时间: 2020 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FT017821%2F1
• 关键词: Support; increased; capacity; facilitate; enhanced

We have known for some time that our by changing the metabolism of the cells in our bodies, diet can directly influence how all of our organs work, and in doing so, affects our long-term health. We also know that the environment that we live in and the stimuli we are exposed to alters our metabolism. Indeed, we have made huge strides recently in characterising how our metabolism can change, as well as whether measurements of the levels of metabolites in our blood or cells can help clinicians make decisions on our health. However, many of the fine details of how exactly our metabolism changes and what this means for our health are unknown. To do this, we trace how nutrients are used in our bodies by enriching them in a naturally-occurring 'heavy' form of carbon or nitrogen, and then following them into different metabolites within cells. This allows us to determine which pathways the nutrients take, and whether changes in this are associated with different diet, age, or even temperature. The equipment that we are requesting in this proposal allows us to detect changes in specific metabolic pathways through identifying alterations in the incorporation of these heavy forms of carbon and nitrogen with very high sensitivity. As it is a very specialised research method, we interact with groups around the UK to support their studies of metabolism in diverse areas of biology, forming a highly collaborative network that benefits research throughout the UK.

我们早就知道，通过改变体内细胞的新陈代谢，饮食可以直接影响我们所有器官的工作方式，并在这样做的同时，影响我们的长期健康。我们也知道，我们生活的环境和我们所暴露的刺激会改变我们的新陈代谢。事实上，我们最近在表征我们的新陈代谢如何变化以及测量我们血液或细胞中的代谢物水平是否可以帮助临床医生对我们的健康做出决定方面取得了巨大的进步。然而，关于我们的新陈代谢到底是如何变化的，以及这对我们的健康意味着什么，许多细节都是未知的。为了做到这一点，我们追踪营养物质在我们体内的使用情况，方法是以自然产生的碳或氮的形式丰富营养物质，然后将它们转化为细胞内的不同代谢物。这使我们能够确定营养物质的途径，以及这种变化是否与不同的饮食、年龄甚至温度有关。我们在这项提案中所要求的设备使我们能够通过以非常高的灵敏度识别这些重形式的碳和氮的结合的变化来检测特定代谢途径的变化。由于这是一种非常专业的研究方法，我们与英国各地的团体互动，支持他们在生物学的不同领域进行新陈代谢研究，形成了一个高度协作的网络，使整个英国的研究受益。

项目成果

High-Resolution Glucose Fate-Mapping Reveals LDHB-Dependent Lactate Production by Human Pancreatic Islets

高分辨率葡萄糖命运图谱揭示了人类胰岛的 LDHB 依赖性乳酸产生

• DOI: 10.2139/ssrn.4398981
• 发表时间: 2023
• 作者: Cuozzo F

Tolerogenic effects of 1,25-dihydroxyvitamin D on dendritic cells involve induction of fatty acid synthesis.

• DOI: 10.1016/j.jsbmb.2021.105891
• 发表时间: 2021-07
• 期刊: The Journal of steroid biochemistry and molecular biology
• 作者: Garcia AM;Bishop EL;Li D;Jeffery LE;Garten A;Thakker A;Certo M;Mauro C;Tennant DA;Dimeloe S;Evelo CT;Coort SL;Hewison M
• 通讯作者: Hewison M

Inflammation causes remodeling of mitochondrial cytochrome c oxidase mediated by the bifunctional gene C15orf48.

• DOI: 10.1126/sciadv.abl5182
• 发表时间: 2021-12-10
• 期刊: Science advances
• 影响因子: 13.6
• 作者: Clayton SA;Daley KK;MacDonald L;Fernandez-Vizarra E;Bottegoni G;O'Neil JD;Major T;Griffin D;Zhuang Q;Adewoye AB;Woolcock K;Jones SW;Goodyear C;Elmesmari A;Filer A;Tennant DA;Alivernini S;Buckley CD;Pitceathly RDS;Kurowska-Stolarska M;Clark AR
• 通讯作者: Clark AR

Loss of SDHB Promotes Dysregulated Iron Homeostasis, Oxidative Stress, and Sensitivity to Ascorbate

• DOI: 10.1158/0008-5472.can-20-2936
• 发表时间: 2021-07-01
• 期刊: CANCER RESEARCH
• 影响因子: 11.2
• 作者: Goncalves, Judith;Moog, Sophie;Favier, Judith
• 通讯作者: Favier, Judith