The Gas-Gangrene Causing Alpha-Toxin: Membrane Interaction and Toxicity

正如媒体经常报道的那样，人们一直在变胖。事实上，到2010年，我们中将有三分之一的人出现临床肥胖症。超重会带来一系列健康风险，包括患II型糖尿病的可能性增加。反过来，糖尿病也有许多并发症，包括腿部和足部更易患长春新症。坏疽的治疗方法是截断感染的腿，而如果不治疗，坏疽总是致命的。这个项目旨在增加我们对坏疽发生在我们体内的了解，从而增加治疗的有效性。气性坏疽主要是由感染伤口的细菌释放的单一毒素引起的。这种毒素附着并攻击人或动物的细胞壁。这种攻击的结果是释放某些信号，导致肢体和身体其他部分发生变化。我们将通过在毒素或细胞壁上附着发光标记，并通过检查毒素的分子结构来研究毒素与人体细胞壁的相互作用。我们将确定毒素的哪些部分使其与细胞壁发生强烈的相互作用。反过来，细胞壁的哪些特征允许毒素附着在细胞壁上。我们将找出如何通过改变细胞壁和/或毒素的特征来改变毒素的行为。这将使我们能够制定策略，在真实案例中模拟毒素的影响。

As is frequently documented in the press, people are getting fatter all the time. In fact, by 2010 one in three of us will be clinically obese. Being overweight carries with it a range of health risks, including an increased likelyhood of developing type II diabetes. Diabetes, in turn, has a number of complications, including increased susceptibility to gengrene of the legs and feet. Gangrene is treated by the amputation of the infected leg, while if left untreated it is invariably fatal. This project aims to increase our understanding of what happens in our bodies once we have gangrene, and thus to increase the effectiveness of the treatment. Gas-gangrene is caused predominantly by a single toxin released by a bacterium that has infected an injury. This toxin attachs to and attacks human or animal cell walls. The result of this attack is the release of certain signals that cause changes in the limb and the rest of your body. We are going to study the interaction between the toxin and human cell walls by using light-emitting markers attached to the toxin or the cell wall and by examining the molecular structure of the toxin.We will identify which parts of the toxin make it interact strongly with cell walls. And, conversely, what features of the cell wall allow the toxin to attach to it. We will find out how we can change the behaviour of the toxin by changing the features of the cell wall and/or the toxin. This will allow us to devise strategies for mitagating the effects of the toxin in real cases.