Why does Drosophila vary in susceptibility to parasitoid wasps?

GSTDTAP

项目编号	NE/P00184X/1
	Why does Drosophila vary in susceptibility to parasitoid wasps?
	[unavailable]
主持机构	University of Cambridge
项目开始年	2017
	2017-01-09
项目结束日期	2020-01-08
资助机构	UK-NERC
项目类别	Research Grant
国家	英国
语种	英语
英文摘要	The aim of this grant is to understand why individuals within populations vary in their susceptibility to infection. This variation determines the burden of disease and allows populations to evolve resistance. For reseatchers, it can provide insights into host-parasite coevolution and functioning of immune systems. We will begin by using high-throughput genome sequencing to identify the genetic variants that make the fruit fly Drosophila melanogaster resistant to its most important natural enemy, parasitoid wasps. These results will be verified by generating genetically identical flies that only differ in the variants in question. We will next identify how these genes make individuals resistant. Hemocytes (blood cells) are the immune cells responsible for killing the parasitoid egg. In resistant flies we have found that hemocytes have moved from sessile clusters associated with neurons into circulation. Furthermore, in our preliminary data we have found a polymorphism in a gene called slit that is strongly associated with resistance. Slit is secreted by neurons and controls cell migration. We will test the hypothesis that resistance is caused by the expression of Slit changing in peripheral neurons so that hemocytes leave sessile clusters and move into circulation, resulting in a constitutively activated immune system that can rapidly kill invading parasitoids. Genetic variation in susceptibility to infection is often thought to be maintained in populations because resistant alleles are costly, but the causes of these costs are poorly understood. We will examine whether costs result from collateral damage caused by a constitutively activated immune system. Flies that are resistant to parasitoids suffer a marked reduction in fitness, and we will use flies that are genetically identical apart from the variants controlling resistance to identify which resistance genes are costly. To test whether it is cellular immune defences that are costly, we can use genetic tools to remove the hemocytes from these flies and examine whether this removes the costs. To test whether it is the release of hemocytes into circulation that is costly, we will use genetic techniques to return the hemocytes of resistant flies to sessile clusters and release the hemocytes of susceptible flies into circulation, and then measure the effect on fitness. Genetic resistance is sometimes effective against a broad range of parasites, but is often highly specific. This specificity is surprising in organisms like insects, as mechanistic studies have found that their innate immune system has limited discriminatory power. To resolve this paradox we will test the hypothesis that genes that alter the magnitude of the innate immune response provide broad-spectrum resistance, while genes that overcome parasite factors sabotaging immunity provide specific resistance. Resistance to parasitoids involves both broad-spectrum and specific resistance genes. By tracking genotype frequencies as populations evolve resistance in the lab, we will identify these genes and confirm the results using genetically engineering flies that are identical except for the variants in question. These flies will allow us to test our prediction that broad-spectrum resistance results from an increase in the magnitude of the innate immune response (number of circulating hemocytes), while specific resistance depends on the susceptibility of hemocytes to wasp venoms that disable the immune system.
来源学科分类	Natural Environment Research
文献类型	项目
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/86625
专题	环境与发展全球科技态势
推荐引用方式 GB/T 7714	[unavailable].Why does Drosophila vary in susceptibility to parasitoid wasps?.2017.