Bad to the Bone: How does the genome control when and where bone grows?

这个博士项目将适合一个学生的前景是一个真正的多学科团队的一部分启发。该项目位于医学，分子生物学，基因组医学和工业之间的界面，是希望进一步提高分子生物学，生物信息学和基因组医学核心技能的人的理想选择。您将开发普通实验室医学技能以及探索非编码序列变异的分子后果的最先进工具。独特的是，iCASE的位置将给你一个补充的经验，在最后期限和目标驱动的临床应用程序开发工作。什么是项目，你会如何参与？身体如何控制何时何地生成骨骼，对生物体的生存和功能至关重要。然而，有时身体会出错，在骨骼外制造骨骼，例如在身体或头部严重受伤后的肌肉中，或者在心脏病中，骨骼实际上可以在血管壁内形成。这个项目是关于了解基因组如何控制这一过程，以及表观遗传学如何影响这种控制。我们以前在遗传关联研究中已经表明，这种疾病有一个遗传成分，发现长非编码RNA基因CASC 20的个体之间的差异通过与多种microRNA（阻止基因工作的遗传物质片段）的相互作用在疾病易感性中发挥作用。在这里，我们计划找出CASC 20使这种错误的骨形成发生的确切分子机制。在这个DiMeN博士研究生项目中，您将加入跨学科和跨机构的，至关重要的是，和工业合作伙伴关系，以确定CASC 20促进病理性骨形成的机制，使我们能够开发新的策略来调节其在衰老疾病中的发展。具体而言，您的项目将解决以下问题：1）CASC 20的下游机制靶基因是什么？2)调节其靶点的CASC 20 RNA功能序列在哪里？3)CASC 20-及其相关microRNA之间的相互作用导致骨形成异常的机制是什么？你将接受什么样的培训？我们对表观遗传学将为我们的人类衰老领域带来的机会充满热情，并希望将我们的热情转移给一个也看到这一领域发展机会的学生。除了在分子生物学和基因组学的具体培训，你将沉浸在一个共同的，复杂的疾病的生物学。您将通过机构间和我们强大的工业合作获得所有这些领域的专业知识。您将有机会参加谢菲尔德和纽卡斯尔的研讨会和系列讲座，以最大限度地利用现有的学习资源。这将包括在谢菲尔德与StemcellX进行一段时间的工业培训，以及在学术机构接受培训。

This PhD Project would suit a student inspired by the prospect of being part of a truly multidisciplinary team. This project sits at the interface between medicine, molecular biology, genomic medicine and industry, and is ideal for somebody who wishes to further core skills in molecular biology, bioinformatics and genomic medicine. You will develop skills in general laboratory medicine as well as state-of-the-art tools in exploring the molecular consequences of non-coding sequence variation. Uniquely, the iCASE placement will give you a complementary experience in deadline and target-driven clinical application development work.What is the project about and how would you be involved?How the body controls where and when bone is made is critical to an organism's survival and function. However, there are times when the body gets it wrong and makes bone outside of the skeleton, for example in the muscles after a severe injury to the body or head, or in heart disease, where bone can actually form within the blood vessel walls. This project is all about understanding how the genome controls this process and how epigenetics can affect that control. We have previously shown in genetic association studies that there is an inherited component to the disease, finding that differences between individuals in the long non-coding RNA gene CASC20 plays a role in disease susceptibility through its interactions with multiple microRNAs (pieces of genetic material that stop a gene working). Here we plan to find out the exact molecular mechanisms through which CASC20 makes this wrong bone formation occur.In this DiMeN PhD studentship, you will join an interdisciplinary and cross-institutional and crucially, and industrial partnership to determine the mechanisms by which CASC20 promotes pathological bone formation, empowering us to develop novel strategies to modulate its development in diseases of ageing. Specifically, your project will address the following questions: 1) What are the downstream mechanistic target genes of CASC20? 2) Where is/are the CASC20 RNA functional sequence/s that regulate its targets? 3) What is the mechanism of the interaction between CASC20-and its associated microRNAs that results in abnormal bone formation?What training will you receive?We feel passionately about the opportunities that epigenetics will bring to our field of human ageing and want to transfer our enthusiasm to a student who also sees the development opportunities in this area. As well as specific training in molecular biology and genomics, you will be immersed in the biology of a common, complex disease. You will gain expertise in all these fields through the inter-institutional and through our strong industrial collaboration. You will have the opportunity to participate in the seminar and lecture series available at Sheffield and Newcastle to maximize the learning resource available. This will including a period of industrial training in Sheffield with StemcellX, as well as that received by the academic institutions.