Microarray analysis for studies of genome organisation and evolution plus development of novel diagnostic tools and technologies

微阵列是一系列微小的DNA斑点以非常有序的方式排列在载玻片上。它可以代表一个完整的基因组，按照它在生物体中出现的顺序排列;它可以由在特定时间在特定组织中表达的部分基因组成，或者它可以包含代表个体生物（如我们自己）中出现的遗传变异的DNA。当我们在这些阵列上进行某些实验时，我们可以更好地了解基因在某些发育时间点何时打开和关闭，人类和动物如何遗传变化以及基因组如何进化。以前，我的研究兴趣集中在染色体的研究上，染色体是细胞分裂时DNA（和相关蛋白质）形成的结构。值得注意的成功包括首次应用染色体技术在胚胎受孕后仅三天诊断遗传疾病，深入了解精子产生和区分鸡的所有染色体（这是第一次在鸟类中实现）。最近，我们一直对细胞不分裂时染色体发生的变化感兴趣，即当细胞执行其正常功能时。将微阵列技术引入我的实验室是一个令人兴奋的机会。原则上，许多技术与染色体上使用的技术非常相似，因此不应该出现量子飞跃，特别是如果我可以参加某些培训课程，让我加快分析所获得结果的协议。这些课程定期举办，例如在剑桥的桑格中心。具体来说，我感兴趣的是开发新的基于微阵列的技术，用于早期发育的遗传诊断;研究鸟类的基因组进化;并询问基因和基因簇的开关如何与它们在细胞核中的空间和时间位置相关。因此，要求提供资金，从我的教学和行政职责中购买我的时间，以重新引导我自己的兴趣和我的实验室对这项新技术的兴趣，更具体地说，使用它提出生物学问题。

A microarray is a series of tiny spots of DNA arranged on a glass slide in a very ordered way. It can represent a whole genome, ordered as it appears in the organism; it can consist of parts of genes that are expressed in certain tissue at certain times or it can contain DNA that represents the sort genetic of variation that would appear in individual organisms such as ourselves. When we perform certain experiments on these arrays we can better understand when genes are switched on and off at certain developmental time-points, how humans and animals vary genetically and how genomes evolve. Previously my research interests have centred around the studies of chromosomes - the structures that form from the DNA (and associated protein) as a cell divides. Notable successes include the first application of a chromosomal technique for diagnosing genetic disease in embryos only three days after they have been conceived, insight in to sperm production and telling all the chromosomes apart in chicken (the first time this had been achieved in a bird). More recently we have been interested in what happens to the chromosomes when the cell is not dividing i.e. when the cell is performing its normal functions. The opportunity to introduce microarray technology into my laboratory is an exciting one. In principle, a lot of the technology is very similar to that used on chromosomes and thus should not present a quantum leap, particularly if I can attend certain training courses to get me up to speed with respect to protocols for analysing the results obtained. These courses are run regularly e.g. at the Sanger Centre in Cambridge. Specifically, I would be interested in developing new microarray-based technologies for genetic diagnosis in early development; investigating genome evolution in birds; and asking how the switching on and off of genes and gene clusters relates to their position in space and time in the nucleus of a cell. Funding is requested therefore to buy out my time from my teaching and administration duties to re-direct my own interests and that of my laboratory towards this novel technology and, more specifically, asking biological questions using it.