Flatworm DNA methylation: deciphering the mark and characterising the machinery.

我们都熟悉遗传学这门学科，它描述了遗传的基本单位(基因)是如何从父母传给后代的。构成我们遗传基因的潜在DNA序列的变化有助于解释为什么会有差异(眼睛颜色、眼睛形状、下巴大小等)。然而，遗传学不能完全解释地球上所有生物所表现出的广泛的表型多样性。为了系统地做到这一点，我们还必须考虑另一种类型的遗传系统，称为表观遗传学。表观遗传学是研究基因功能的遗传变化(导致不同的表型)，这些变化不能用基因潜在DNA序列的变化来解释。换句话说，表观遗传学试图解释遗传学无法解释的一切。DNA甲基化是导致表型遗传变化的一种特殊的表观遗传过程。DNA甲基化调控的缺失在人类中得到了广泛的研究，并与癌症、肥胖、免疫缺陷和智力残疾有关。最近的研究还表明，可遗传的DNA甲基化模式受到我们与环境(化学品、药物等)相互作用的影响。各种因素。然而，人们对DNA甲基化或其他动物系统中调节DNA甲基化的过程知之甚少，尤其是无脊椎动物。平虫是一个非常重要的无脊椎动物群体(在扁形蠕虫门中)，导致许多经济和生物医学相关的寄生虫病。这些寄生无脊椎动物在其复杂的生命周期中经历了广泛的发育变化，这往往涉及到与不止一个宿主或环境的相互作用。环境影响的DNA甲基化是否有助于这些寄生虫的成功？如果是这样的话，这是如何发生的，这种表观遗传机制针对的是哪些基因？在Aberystwyth，我们将应用最先进的分子生物学工具来尝试和了解DNA甲基化如何调节扁虫的发育。我们已经发现，DNA甲基化存在于所有三类寄生扁形虫中(吸虫目、Cestoda目和单殖目)，负责这些基因组修改的酶是高度保守的。使用一个模式扁虫(曼氏血吸虫)，我们的项目旨在进一步表征负责扁虫DNA甲基化的酶，并识别DNA甲基化机制专门针对的基因。通过以协同的方式这样做，我们希望在动物进化过程中发现这种表观遗传过程的新角色。这些信息可能最终会导致对抗寄生虫病的新方法。

We are all familiar with the subject of genetics, which describes how the fundamental unit of inheritance (the gene) is passed on from parent to offspring. Changes in the underlying DNA sequence that make up our inherited genes help explain why differences (eye colour, eye shape, chin size, etc.) in our outward appearance (phenotype) occur.However, genetics cannot fully explain the wide-ranging phenotypic diversity exhibited by all organisms on this planet. To do so in a systematic manner, we also have to consider another type of inheritance system called epigenetics. Epigenetics is the study of inherited changes in gene function (leading to different phenotypes) that cannot be explained by changes in the underlying DNA sequence of the gene. In other words, epigenetics attempts to explain everything that genetics cannot. One particular type of epigenetic process responsible for inherited changes in phenotype is facilitated by DNA methylation. Loss of DNA methylation regulation has been extensively studied in humans and is associated with cancer, obesity, immunodeficiencies and intellectual disabilities. Recent studies have additionally demonstrated that heritable DNA methylation patterns are influenced by our interaction with environmental (chemicals, drugs, etc.) factors. However, very little is known about DNA methylation or the processes that regulate it in other animal systems, especially invertebrates.Flatworms are a tremendously important invertebrate group (within the phylum Platyhelminthes) responsible for many economically- and biomedically-relevant parasitic diseases. These parasitic invertebrates undergo extensive developmental changes throughout their complicated lifecycles, which often involves interaction with more than one host or environment. Does environmentally influenced DNA methylation contribute to the success of parasites like these? If so, how does this occur and what genes are targeted by this epigenetic mechanism?Working in Aberystwyth, we will apply state of the art molecular biology tools to try and understand how DNA methylation regulates flatworm development. We have already found that DNA methylation is present in all three classes (Trematoda, Cestoda and Monogenea) of parasitic platyhelminth and that the enzymes responsible for these genome modifications are highly conserved. Using a model platyhelminth (Schistosoma mansoni), our project aims to further characterise the enzyme responsible for flatworm DNA methylation and to identify the genes specifically targeted by the DNA methylation machinery. By doing so in a synergistic manner, we expect to discover new roles for this epigenetic process during animal evolution. This information may eventually lead to novel ways to combat parasitic diseases.