Epigenetic regulation of DNA repeats and genome stability in Candida albicans

白色念珠菌是一种机会性真菌（酵母的一种形式），通常生活在人体上，不会造成任何伤害。然而，白色念珠菌可以引起毁灭性的疾病，特别是在免疫功能低下的患者谁接受器官移植，化疗，或艾滋病毒治疗。致病性白色念珠菌能有效适应不同的环境，并能获得抗真菌药物的耐药性。这是因为，与大多数生物相比，白色念珠菌可以在没有适当比例的基因的情况下生存，甚至可以失去一部分染色体（一种称为基因组可塑性的现象）。人们发现重排经常发生在重复DNA序列的特定位置。我们想了解为什么DNA重复序列是染色体重排的位点。在大多数生物体中，DNA重复会给细胞带来麻烦。这是因为重复序列往往是“不稳定的”，可以与基因组中其他位置的重复序列相互作用和融合。这意味着基因组可以自我重组，导致一些序列的丢失和其他序列的复制。它还可以将基因组的两个独立部分结合在一起，这可能会扰乱制造适量蛋白质的指令。基因组重排是癌细胞和出生缺陷的标志。为了对抗DNA重复序列对基因组的潜在威胁，生物体已经开发出对抗DNA重复序列不稳定性的策略。一种策略是将重复序列包裹在保护性蛋白质中，以防止它们与其他重复序列相互作用。这种保护性蛋白质结构被称为“异染色质”。对于某些生物体，如微生物病原体，在某些环境条件下可以方便地重新排列它们的基因组，因此可以暂时从DNA重复序列中抹去异染色质。白色念珠菌可能是其中一种，我们将验证这一假设。我们将询问白色念珠菌的DNA重复序列是否通常通过被包裹在异染色质中而保持在“安全”状态，以及白色念珠菌是否可以剥离这些蛋白质，从而使基因组在有利条件下重排，从而使白色念珠菌成为病原体。

Candida albicans is an opportunistic fungus (a form of yeast) that normally lives on the human body without causing any harm. However, C. albicans can cause devastating diseases especially in immunocompromised patients who have undergone organ transplants, chemotherapy, or HIV treatment. Pathogenic C. albicans adapts efficiently to different environments and it can acquire resistance to anti-fungal drugs. This is because, in contrast to most organisms, C. albicans can live without the right proportion of its genes or even miss a part of a chromosome (a phenomenon called genome plasticity). It was discovered that rearrangements often occur at particular sites of repetitive DNA sequences. We want to understand why DNA repeats are sites of chromosome rearrangement. In most organisms, DNA repeats spell trouble for the cell. This is because repetitive sequences tend to be 'unstable' and can interact and fuse with other repeat sequences in other places in the genome. This means the genome can rearrange itself, causing loss of some sequences and duplication of others. It can also bring two separate sections of the genome together, which can mess up the instructions for making the right amount of proteins. Genome rearrangements are a hallmark of cancer cells and birth defects. To counteract the potential threat to the genome by DNA repeats, organisms have developed strategies to fight against the instability of DNA repeats. One strategy is to coat the repetitive sequences in protective proteins that prevent them from interacting with other repetitive sequences. This protective protein structure is called 'heterochromatin'. For certain organisms, such as microbial pathogens, it can be convenient in certain environmental conditions to rearrange their genomes and therefore to temporarily erase heterochromatin from DNA repeats. C. albicans could be one of these organisms and we will test this hypothesis. We will ask whether C. albicans DNA repeats are usually kept in a 'safe' state by being coated in heterochromatin and if C. albicans can strip these proteins off to allow the genome rearrangements in favourable conditions to cause C. albicans to become a pathogen.