Introgressing beneficial genes into populations

The astonishing recent advances of molecular genetics, together with the new data from genomic sequencing programs, give us an unprecedented ability to manipulate the genotypes and phenotypes of plants and animals. This in turn holds out the prospect that some of the ancient scourges of mankind, the pests and diseases of humans, crops and livestock, might be controlled by genetic manipulation of the causative organisms, their vectors or wild reservoirs. To an extent, this has begun to be realised in the case of GM crops, for example the insecticidal Bt crops. However, while we can disseminate new genes in populations where we have complete control of their reproduction and location, for example crops and most livestock, we have no capacity to introgress genes into wild populations. Multiple research groups are attempting to identify in the laboratory genes and constructs which, if present in a wild population of a disease vector, would eliminate or dramatically reduce disease transmission. The pace of current research suggests that within a decade, and probably much sooner, many such systems will be available. This research is focused at present on mosquito-borne diseases, but is equally applicable to various diseases of plants and livestock. However, while progress in the area of aniti-pathogen effectors has been very encouraging, there is as yet no method to introgress these genes into wild populations, in other words to use them. This has been identified by some as a fatal flaw in the entire 'refractory insect' strategy. The problem is as follows. It is highly likely that any such genetic construct, for example one which reduces the capacity of vector species to transmit pathogens, will have a fitness cost associated with it. This means the genetically altered vector will be at a selective disadvantage relative to the wild type that it is intended to replace. Thus, if the refractory strain were simply released into the field it would be selected against, relative to the wild type, and so the desired trait would not spread. While it is possible that the trait itself may confer a selective advantage, for example by allowing the engineered vectors to avoid fitness costs associated with carrying pathogens, this is unlikely. Thus, an engineered refractory construct is unlikely to spread through a wild population unaided. Rather, an effective system for driving the construct into wild vector populations is essential in order to bring the 'refractory insect' strategy to practical utility. Such systems are generically termed 'gene drive' systems, or 'gene drivers'. For many reasons, not least regulatory, it is desirable that the gene drive system is not too invasive, in other words will stay where you put it, at least within some definable parameters. One of the few systems to have been described with this property, at least in theory, is the 'underdominance'-based system of Davis et al (2001). The student will develop the key tools necessary to produce an underdominance-based gene drive system. The project will involve confined and theoretical studies only. Specifically, this requires the design and construction of pairs of mutually suppressing dominant lethal genetic elements. Oxitec's work on repressible lethal systems for control of agricultural and public health pests will form the foundation for this. The work will initially be conducted in the mosquito Aedes aegypti. This species was selected for its combination of interest in / need for gene drive systems, availability of the genome sequence to facilitate the identification of the necessary molecular tools, and Oxitec's previous investment in developing genetic tools and methods for this species. Davis, S., Bax, N., and Grewe, P. (2001). Engineered underdominance allows efficient and economic introgression of traits into pest populations. J theor Biol 212, 83-98.