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

这个博士生项目将适合那些希望成为真正的多学科团队的一员而受到启发的学生。该项目位于医学、分子生物学、基因组医学和工业的交界处，是希望进一步掌握分子生物学、生物信息学和基因组医学核心技能的人的理想选择。你将发展普通实验室医学的技能，以及探索非编码序列变异的分子后果的最先进的工具。独一无二的是，iCASE植入将在截止日期和目标驱动的临床应用开发工作中为您提供补充经验。该项目关于什么，您将如何参与？身体如何控制何时何地制造骨骼对有机体的生存和功能至关重要。然而，有时身体会犯错，在骨骼之外制造骨骼，例如在身体或头部严重受伤后在肌肉中，或者在心脏病中，骨骼实际上可以在血管壁内形成。这个项目是关于理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。我们之前在遗传关联研究中已经表明，这种疾病存在遗传成分，发现个体之间的差异通过与多个microRNAs(阻止基因工作的遗传物质)相互作用，在长非编码RNA基因CASC20中发挥作用。在这里，我们计划找出CASC20使这种错误的骨形成发生的确切的分子机制。在这个地门博士研究生中，你将加入一个跨学科和跨机构的、关键的和行业合作伙伴关系，以确定CASC20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。具体来说，您的项目将解决以下问题：1)CASC20下游的机械性靶基因是什么？2)调节其靶基因的CASC20-RNA功能序列/S在哪里？3)CASC20-与其相关的microRNA之间的相互作用导致异常骨形成的机制是什么？您将接受什么培训？我们对表观遗传学将为我们的人类老龄化领域带来的机遇充满热情，并希望将我们的热情转移到一个也看到这一领域发展机会的学生身上。除了分子生物学和基因组学方面的专门培训外，你还将沉浸在一种常见、复杂疾病的生物学中。您将通过机构间和我们强大的行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，以最大限度地利用可用的学习资源。这将包括在谢菲尔德与Stemcell X一起进行一段时间的工业培训，以及学术机构接受的培训。

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.