Identifying the underlying mechanisms of medium chain fatty acids in health using a simple model system
使用简单的模型系统识别中链脂肪酸对健康的潜在机制
基本信息
- 批准号:1813968
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:英国
- 项目类别:Studentship
- 财政年份:2016
- 资助国家:英国
- 起止时间:2016 至 无数据
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The medium chain tryglyceride (MCT) ketogenic diet provides a range of health benefits including improved behaviour and cognitive function (1), and is a treatment for drug resistant epilepsy, and possibly brain cancer and Alzheimer's disease treatment (2,3). The diet involves the supplementary intake of two main medium chain fats, decanoic and octanoic acid and was thought to act through the generation of ketones (4,5). However, we have recently demonstrated that it acts in epilepsy treatment through a direct effect of decanoic acid on a neurotransmitter receptor. The other mechanisms of actions relating to health remain to be defined. Identifying these mechanisms will significantly improve our understanding of the health benefits of the diet that is a priority area for BBSRC research.Our studies provide world-leading examples of using the simple eukaryote, Dictyostelium, as an innovative animal-replacement model in a range of biomedical-related studies (6). Examples of our breakthroughs include: a) Identifying the molecular mechanism of the epilepsy treatment valproic acid in Dictyostelium (7,8) and the translation of this to in vitro and in vivo animal models (9), leading to the identification novel potent compounds with efficacy in multiple animal models (10,11), with two resulting patents (WO_2012069790_A1, GB_Application_1416017.0) and the discovery of the target of decanoic acid in epilepsy control (12). Clinical trials relating to this discovery are due to start in early 2016. b) Identifying targets for bitter tastants related to drug development and therapeutic activity (13,14). c) Illustrating the conserved roles of homologues of two health/disease related human proteins (13,15).These animal-replacement studies suggest that Dictyostelium can inform our understanding of cellular functions of food relevant to human health, and this is another priority area for BBSRC funding.The project will involve screening a Dictyostelium mutant library to identify proteins controlling the effect of these food related fats. Fat-dependent changes in cell function will be investigated to identify molecular mechanism of these foods. Human homologues of the identified proteins will be analyse in Dictyostelium, and mammalian cell lines will be used to provide translational research and lead to the analysis of human samples.The project will provide advanced training in a multidisciplinary range of techniques, including cell and developmental biology, biochemistry, pharmacology, and pharmacogenetics and outstanding training in 3Rs research and its broad application. The student will also be trained in traditional (mammalian) cell models, providing a new integrated way of working in 3Rs research, in addition to scientific writing and oral presentation at international meetings (the annual International Dictyostelium meeting).
中链甘油三酯(MCT)生酮饮食提供了一系列健康益处,包括改善行为和认知功能(1),并且是耐药性癫痫的治疗方法,也可能是脑癌和阿尔茨海默病的治疗方法(2,3)。饮食包括补充摄入两种主要的中链脂肪,癸酸和辛酸,并被认为是通过酮的产生(4,5)。然而,我们最近已经证明,它通过癸酸对神经递质受体的直接作用来治疗癫痫。与健康有关的其他行动机制仍有待确定。确定这些机制将大大提高我们对饮食的健康益处的理解,这是BBSRC研究的优先领域。我们的研究提供了世界领先的使用简单真核生物Dictyosteoblast作为一系列生物医学相关研究中的创新动物替代模型的例子(6)。我们的突破包括:a)确定丙戊酸在网骨藻中治疗癫痫的分子机制(7,8),并将其转化为体外和体内动物模型(9),从而确定了在多种动物模型中有效的新型强效化合物(10,11),并获得了两项专利(W0_2012069790_A1,GB_Application_1416017.0)和发现癸酸在癫痫控制中的靶标(12)。与这一发现相关的临床试验将于2016年初开始。B)鉴定与药物开发和治疗活性相关的促苦味剂的靶标(13,14)。c)阐明两种与健康/疾病相关的人类蛋白质同源物的保守作用(13,15)。这些动物替代研究表明,网囊藻可以为我们了解与人类健康相关的食物细胞功能提供信息,这是BBSRC资助的另一个优先领域。该项目将涉及筛选网囊藻突变体库,以确定控制这些食物相关脂肪影响的蛋白质。将研究细胞功能的脂肪依赖性变化,以确定这些食物的分子机制。该项目将提供多学科技术的高级培训,包括细胞和发育生物学、生物化学、药理学和药物遗传学,以及3Rs研究及其广泛应用方面的优秀培训。学生还将接受传统(哺乳动物)细胞模型的培训,提供3Rs研究的新综合工作方式,以及科学写作和国际会议(年度国际网骨藻会议)的口头报告。
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)
All You Need Is Fats-for Seizure Control: Using Amoeba to Advance Epilepsy Research.
您所需要的只是癫痫发作控制:使用变形虫来推进癫痫研究。
- DOI:10.3389/fncel.2018.00199
- 发表时间:2018
- 期刊:
- 影响因子:5.3
- 作者:Warren EC;Walker MC;Williams RSB
- 通讯作者:Williams RSB
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其他文献
吉治仁志 他: "トランスジェニックマウスによるTIMP-1の線維化促進機序"最新医学. 55. 1781-1787 (2000)
Hitoshi Yoshiji 等:“转基因小鼠中 TIMP-1 的促纤维化机制”现代医学 55. 1781-1787 (2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
LiDAR Implementations for Autonomous Vehicle Applications
- DOI:
- 发表时间:
2021 - 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
吉治仁志 他: "イラスト医学&サイエンスシリーズ血管の分子医学"羊土社(渋谷正史編). 125 (2000)
Hitoshi Yoshiji 等人:“血管医学与科学系列分子医学图解”Yodosha(涉谷正志编辑)125(2000)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Effect of manidipine hydrochloride,a calcium antagonist,on isoproterenol-induced left ventricular hypertrophy: "Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,K.,Teragaki,M.,Iwao,H.and Yoshikawa,J." Jpn Circ J. 62(1). 47-52 (1998)
钙拮抗剂盐酸马尼地平对异丙肾上腺素引起的左心室肥厚的影响:“Yoshiyama,M.,Takeuchi,K.,Kim,S.,Hanatani,A.,Omura,T.,Toda,I.,Akioka,
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
的其他文献
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2896097 - 财政年份:2027
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2780268 - 财政年份:2027
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2908693 - 财政年份:2027
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2908917 - 财政年份:2027
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2879438 - 财政年份:2027
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Developing a 3D printed skin model using a Dextran - Collagen hydrogel to analyse the cellular and epigenetic effects of interleukin-17 inhibitors in
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2876993 - 财政年份:2027
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