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面试官: Diabetes and fruit flies; Dr. 卡尔Thummel, Professor of Human Genetics, is investigating what these insects can tell us about the disease, and some of his findings may surprise you.
这是发生在苍蝇身上的事情，还是你在实验室里诱导的事情?
Dr. Thummel: It can happen under any circumstances, just like it could with you and me, because all living animals fundamentally need to handle their energy. 所以大发娱乐一天吃三顿饭，大发娱乐这样做是因为大发娱乐需要能量来生存. And we take those nutrients; we burn some of them to do what we need to do day to day, just to maintain our normal existence. 大发娱乐储存了大量的脂肪，这样当食物不充足的时候，大发娱乐就可以使用它们. And all animals have to do this, so that when we are fasting, or starving under the worst conditions as an animal, 大发娱乐可以生存. It's just a fundamental survival mechanism, 有监管系统控制能量的储存和释放, and 他们是 the same in a fly or a person.
面试官: And what does a fly with diabetes look like?
Dr. Thummel: Diabetes would not necessarily lead to being overweight. 很多人问你是否能分辨出你的苍蝇是肥胖的，很遗憾你不能. But I just wonder if it's because we're not flies.
面试官: 是的.
Dr. Thummel: 你知道，当你看着它们的时候，另一只苍蝇可能会看着你说，你看起来超重了. 什么是错的? 但是当大发娱乐观察这些苍蝇时，大发娱乐并没有看到它们在视觉上超重, and it might be because they have an exoskeleton.
面试官: 正确的.
Dr. Thummel: 不像大发娱乐, we have a skeleton inside our body; they have a skeleton outside their body that restricts their size to some degree.
面试官: 正确的.
Dr. Thummel: 但如果你打开它们，看看它们的脂肪沉积，你会发现它们确实富含脂肪. 大发娱乐可以用测量甘油三酯的方法来测量, which are stored fat. And that's how we quantify it basically.
播音员: What's the advantage of investigating diabetes in fruit flies?
Dr. Thummel: That's the real question, right? 为什么大发娱乐要研究你和我在这个奇怪的小细菌系统中出现的这些疾病呢? And that's where the real strength comes in, 因为果蝇在基因和功能研究上有很多优势. 它们只是不存在于其他更复杂的动物模型中，比如老鼠，甚至斑马鱼.
This goes back to about 100 years now of fly genetics that's behind this, 成千上万的基因储备可供大发娱乐使用，所以大发娱乐可以以任何大发娱乐想要的方式快速地操纵苍蝇的基因组, and analyze pathways in great detail... far greater than we could do in another model system.
面试官: And can you tempt us with any of your findings?
Dr. Thummel: We're excited about our studies with diabetes now, because we have one of the first genetic models of diabetes. 大发娱乐有遗传性糖尿病模型，通过突变，这些动物不再能够正确地释放胰岛素来应对葡萄糖, which is what normally happens. 你吃了一顿饭, your glucose levels rise, your pancreatic cells sense that and release insulin, and that causes your peripheral tissues to suck up glucose, to store it away or burn it. And the diabetics are unable to do that for various reasons, either an inability to release insulin properly, or an inability to clear glucose properly. And our different genetic models have defects in both of those pathways. 它们不能感知葡萄糖或释放胰岛素，也不能正常清除外周组织中的胰岛素.
所以大发娱乐可以建立比大发娱乐实际期望的更多的模型, really model the major forms of diabetes that are out there. 所以大发娱乐真的在努力工作，试图找出其中的机制. Many of the genes we identify are conserved throughout evolution, and so we think it'll have direct relevance for human disease.
面试官: 我注意到你正在研究的一件事是糖尿病的跨代影响, which is a concept that's really fascinating to me. Can you explain what that is and what you're doing?
Dr. Thummel: This goes back to studies in rodent systems over the last decades, but more profoundly to a human study called the Dutch Hunger Winner, 那是在第二次世界大战结束时，纳粹正在围攻荷兰. And the Dutch were getting much less food than they normally would get. 那些出生在营养匮乏时期的孩子长大后生活在战后经济繁荣的理想饮食环境中. 结果是，当你把这些孩子作为成年人来看，那些母亲营养不足的孩子比他们的兄弟姐妹更容易患糖尿病和肥胖, who where under ideal dietary circumstances.
这很有趣，因为许多研究在大鼠和小鼠身上都显示了同样的情况. And people hadn't really known what to make out of it.
面试官: 正确的, because it's not like traditional genetics. The parents weren't born with a predisposition to diabetes; they acquired it later. But then they still passed it on to their kids.
Dr. Thummel: You're exactly right. 所以这意味着大发娱乐自己的代谢健康不仅仅取决于大发娱乐吃什么和大发娱乐特定的基因, 就像大发娱乐假设的那样. 这些是大发娱乐认为最重要的事情，它们确实是. 但影响大发娱乐代谢健康的另一个重要因素是大发娱乐父母的代谢健康，甚至是大发娱乐祖父母或曾祖父母的代谢健康.
This has been now receiving a lot of attention. 人们想要了解这种非规范遗传背后的分子机制, called epigenetic inheritance. And we are tackling it in the fruit fly.
面试官: What's an example of how you're approaching that problem in flies?
Dr. Thummel: 大发娱乐已经建立了基因完全相同的果蝇种群, so there's no genetic variation in those. And we are taking the parental generation and subjecting them either genetically or through diet to nutrient deprivation; or we're making them conversely obese; too much nutrients. 然后大发娱乐用正常的饮食喂养它们的后代，并检查它们的代谢参数. 大发娱乐选取它们的后代，给它们正常的饮食，并检查它们的代谢参数, 等等.......
So we are looking to reproduce the effects in rodents and humans. We have been successful at that, 所以现在大发娱乐要做的就是让这些结果足够的可重复和可靠，这样大发娱乐就可以开始做分子研究来获得一个机制.
面试官: You've been working with fruit flies for quite a while, and I believe this is sort of a new focus for your lab, a relatively new focus. Why did you decide to make that shift?
Dr. Thummel: 大家都知道, and as everyone knows, 在过去的十年里，大发娱乐已经非常清楚地意识到糖尿病和肥胖症在人类人口中的增长. 它确实以大发娱乐从未想象过的方式威胁着大发娱乐的健康. 当我还是个孩子的时候，大发娱乐可以吃Twinkies和喝可口可乐，大发娱乐甚至没有考虑过这些对健康的影响. 太棒了.
面试官: 是的.
Dr. Thummel: 现在大发娱乐看着大发娱乐的孩子，大发娱乐实际上担心他们是否喝了太多的苏打水, or are they eating too many junk foods, 事实上, 他们是. 作为一个群体，大发娱乐有比日常生存所需更多的卡路里, so we are all living in an epidemic of diabetes and obesity. You can see it around you all the time.
And so this peaked our interest, 这让大发娱乐重新定位了大发娱乐的研究方向，看看大发娱乐能在多大程度上推动果蝇研究这些进化上保守的途径. And it's been very gratifying to see how well we can model it. Actually it's really surprising, I'll have to say. I am very surprised to see how similar 他们是.
播音员: Interesting, informative, and all in the name of better health. This is 范围 Health Sciences Radio.