Ecological and functional importance of novel virus genes expressed during infection of the globally important microalga, Emiliania huxleyi

我们正在研究一种微小的海洋生物，它可以自由地漂浮在海洋中，并使自己成为一个白垩质的外壳，其外壳由称为球壳的鳞片组成。当条件合适时，这种被称为颗石浮游生物（学名Emiliania huxleyi）的微小浮游生物可以大量生长（在一茶匙海水中多达10，000），形成所谓的“水华”。在这些巨大而令人印象深刻的花朵中，球石反射的光甚至可以从太空中看到;它们可以是一个小国到整个大陆的大小。不幸的是，只有当细胞死亡，白垩壳被释放到周围的海洋中时，才能从太空中看到这些水华。当这种情况发生时，大海看起来是乳白色的白色！多佛的白色悬崖上的白垩，集中体现在维拉夫人林恩著名的战争歌曲中，是由死去的E。huxleyi。我们已经成功分离出一种巨大的病毒（甚至藻类也会生病！）导致了这些颗石藻的死亡为了大量复制自己，我们的巨型病毒必须进入一个单一的海洋细菌细胞，劫持细菌的复制机制来复制自己的病毒基因组（所有的病毒基因都在一个单一的环形DNA片段上）。一旦病毒在（现在已经病入膏肓的）细胞内复制了几百个自己的基因组，它就变成了一个蛋白质工厂，生产所有的蛋白质组成部分。然后，所有这些部分整齐地组装成数百种全新的病毒，这些病毒将（现已死亡的）细胞炸开。每一种病毒都携带一份自己的基因组和一些额外的蛋白质和脂肪，以便在感染下一个毫无戒心的健康个体时沿着。然后重复这个过程，直到几乎所有的藻类在颗石藻水华死亡。病毒基因组是一段很长的DNA，分为称为基因的较小区域。每个基因都包含创造蛋白质所需的特定信息（基因为蛋白质编码/将基因视为蛋白质的蓝图）。通常情况下，病毒的基因组很小，只有少量的基因，这就是为什么它们可以如此快速地复制。例如，导致艾滋病的人类免疫缺陷病毒（HIV）只有9个基因。我们的杀藻病毒真的是一个巨人，因为它有大约480个基因。但我们不知道病毒中的大多数基因是做什么的。它们不同于任何其他已知的基因。我们所知道的一些基因非常不寻常，以前从未在病毒中发现过。在这项研究中，我们想找出为什么这种病毒有不寻常的基因，并找出它们的作用。一组基因编码我们认为是杀死不幸感染的蚊子的信号。这是一种被称为细胞凋亡或程序性细胞死亡（当蝌蚪变成青蛙时尾巴消失）的机制，以前从未在病毒中观察到过。这一重要发现将吸引科学家寻找杀死细胞的新机制，并可能应用于抗癌疗法的开发。在这项研究中，我们将找出为什么这种病毒使用凋亡基因，以及这些基因编码的蛋白质如何共同作用杀死海洋生物。我们还想知道这些蛋白质是否有其他功能;例如，它们可能是海洋食物链中重要的营养来源。受感染的蝗虫将成为食物链底部的小型食肉动物的美味佳肴。为了做到这一点，我们将使用化学和基因组学（当你同时查看所有基因时使用的术语）的组合来找出病毒和宿主中基因是如何一起工作的。

We are working on a tiny marine alga that floats freely in the ocean and makes itself a chalky outer shell from scales known as coccoliths. When conditions are right, this tiny alga, referred to as coccolithophore plankton (scientific name Emiliania huxleyi) can grow in huge numbers (up to 10,000 in a teaspoonful of seawater) to form what is known as a 'bloom'. Light reflected by coccoliths in these massive and impressive blooms can even be seen from space; they can be the size of a small country to a whole continent. Unfortunately the blooms can only be seen from space when the cells are dying and the chalky shell is released into the surrounding sea. When this happens the sea looks a milky white colour! The chalk of the White Cliffs of Dover, epitomised in Dame Vera Lynn's famous war time song, are formed from the coccoliths of dead E. huxleyi. We have managed to isolate a giant virus (even algae can get ill!) that is responsible for the death of these coccolithophore blooms. In order to make lots of copies of itself, our giant virus has to get inside a single marine alga cell, hijack the alga's replication machinery to make lots of copies of its own virus genome (all the virus genes on a single circular piece of DNA). Once the virus has made several hundred copies of its own genome inside the (now very sick) alga cell, it turns into a protein factory manufacturing all its protein component parts. All these parts are then neatly assembled into hundreds of brand new viruses that burst open the (now dead) alga cell. Each virus takes a copy of its own genome and some extra protein and fat baggage to help it along when it infects the next unsuspecting healthy alga. This process is then repeated until nearly all of the algae in the coccolithophore bloom are dead. The virus genome is a long stretch of DNA divided into smaller regions called genes. Each gene contains the specific information needed to create a protein (genes 'code' for proteins / think of genes as a protein 'blueprint'). Normally viruses have small genomes and only a small number of genes, which is why they can replicate so quickly. For example the devastating Human Immunodeficiency Virus (HIV) that causes AIDS has only 9 genes. Our alga-killing virus really is a giant because it has around 480 genes. BUT we don't know what most of the genes in our virus do. They are unlike any other known genes. Some of the genes we do know about are very unusual and have never been seen in a virus before. In this study we want to find out why this virus has unusual genes and work out what they do. One group of genes code for what we believe is a signal to kill the unfortunate infected alga. It is a mechanism termed apoptosis, or programmed cell death (seen when a tadpole's tail disappears as it turns into a frog) and has never been observed in a virus before. This important discovery will interest scientists looking for novel mechanisms for killing cells and may have applications in development of anti-cancer therapies. In this study we will find out why this virus uses apoptosis genes and how the proteins encoded by these genes work together to kill the marine alga. We also want to find out if these proteins have any other function; for example they may act as an important source of nutrition in the marine food chain. Infected alga will make a tasty meal for small alga eating animals at the bottom of the food chain. To do this we are going to use a combination of chemistry to find out what the food source is and genomics (a term used when you look at all the genes all at the same time) to find out how the genes work together in both the virus and host.