Mosquitoes, fruit flies and infections

04 October 2012

Interview with

Dr Frank Jiggins, University of Cambridge

Now it's time to take a look at some other insects.  Not only do mosquitoes keep you awake with their annoying hum and painful bites, they're also a major channel for the spread of diseases in many parts of the world including malaria and dengue fever.  

At the University of Cambridge, Dr. Frank Jiggins is investigating why some insects are susceptible to infection with disease-causing parasites and why others aren't.  As well as studying mossies directly, he's also looking at some rather less annoying and dangerous insects as a model - fruit flies.  I started by asking him what sort of diseases fruit flies could pick up?

Frank::  Fruit flies have lots of parasites and pathogens.  So, we particularly work on viruses and they also have parasitic wasps which lay their eggs within the fruit fly larvae and then the wasp will develop and devour the fruit fly larva from within.  Insects also have a very sophisticate immune system so you sometimes find genetic variation in their immune response.  So, some individuals have more effective immune responses.  But then also, particularly for viruses, the virus relies on using lots of host molecules and lots of insect molecules in order to complete its own life cycle.  So, evolution can change the insect proteins which the virus is using for its own benefit, in a way that makes insects resistant to infection.

Kat::  What sorts of viruses are these that infect fruit flies?  I can't imagine a fruit fly with a cold.

Frank::  Well, it turns out that in fact, fruit flies have an enormous diversity of viruses.  So, there's only two or three which are well-understood and that we work with in the lab.  But in fact, if you look and you sequence viruses from fruit flies, they have a diversity of viruses, many of which are related to things like rabies in vertebrates, and a whole range of other viruses which infect us.  So in fact, they have lots of different viruses.  Many of which are very similar to viruses which we get.

Kat::  Now, you think that it would be quite a big advantage if an organism, an insect say, was resistant to viruses.  Why do we still see such variation in populations?  Why haven't the susceptible individuals just been bred out?

Frank::  Yes, so you'd expect due to natural selection that you'd end up with everyone in the population becoming resistant and then you wouldn't be left with any susceptible individuals.  So, there's two possible reasons why you'd still get susceptible individuals.  So, one possibility is that being resistant is very costly.  It might take a lot of resources or you might suffer from autoimmune disease if you have a very active immune system.  So it might be that for some individuals, it's better to be susceptible and take the risk of becoming infected to avoid all those costs of being resistant.  But one thing which we're finding with viruses, is that the reason why you see so much variation is that the parasite itself keeps changing.  

So, as soon as the insect evolves to become resistant, then the parasite or the virus will change and overcome that resistance.  So this leads to an evolutionary arms race as the host or the insect needs to keep evolving new ways of becoming resistant.  So you get new genes arise or changes to genes in the insect population and these are continually spreading through the population.  So, when we turn up and we look at that population, we see lots of variation and that's because the resistance genes are spreading through the population as the susceptible individuals are being killed off by the infection.

Kat::  Tell me a bit about the work you're doing in mosquitoes.  How do some mosquitoes become resistant to say, malaria parasites or other parasites?

Frank::  Other people have worked on malaria and they found that there's a variation in some of the immune genes which recognise malaria parasites and that means that some mosquitoes in populations resistant and can transmit malaria and others are susceptible and do transmit malaria.  So, we've been working on a mosquito which transmits lymphatic filariasis which is caused by a small nematode worm, and we find we haven't yet found the gene, but we find there's a single gene which controls resistance to this worm.  It's got very, very simple genetics.  So we're currently trying to identify which gene it is which is preventing some mosquitoes from transmitting the infection.

Kat::  Presumably then, maybe you could breed or select mosquitoes that don't transmit the infection, release them into the wild, and hope that it would reduce the transmission of the disease?

Frank::  So that's really the difficult bit.  So finding the genes is the easy bit.  So finding out why you get resistance in susceptible things is easy.  The difficult thing is then trying to modify the mosquito populations so that they all become resistant.  So one possibility people have suggested is you might be able to use some sort of genetic modification which would allow the genes to spread through populations.  Another thing which has caused a lot of excitement recently is it's being discovered that bacterial symbionts can also make mosquitoes resistant to particularly RNA viruses which can cause things like dengue fever.

Kat::  What do you mean by bacterial symbiont?  What's that?

Frank::  So, these are bacteria which infect insects and they're particularly bacteria in a group called Wolbachia.  They're found in about 40 per cent of all insect species and they're transmitted through eggs, so they go from mother to offspring every generation.  And the advantage of this bacteria is firstly, they very often protect the insects from the RNA viruses which means if you put these bacteria into mosquitoes, they can't transmit dengue fever.  But also, they have tricks by which they can spread through populations.

Kat::  So then maybe if we could spread these bacteria through the population that would also be a really good way of getting resistance.

Frank::  Yes, so what people have done in Australia is they took a Wolbachia which had been first identified in fruit flies and made fruit flies resistant to viruses.  They put it in some mosquitoes and there they found firstly, it made the mosquitoes resistant to dengue fever but secondly, they also released these mosquitoes in the populations in Australia and they found that when they'd released enough infected mosquitoes, the bacterium started spreading through the mosquito population.  So you can see that hopefully, this might lead to a way in which we could spread the bacteria through natural populations of mosquitoes and potentially interrupt the transmission of diseases like dengue fever.

Kat::  But until that day, we'll just have to keep swatting them?

Frank::  Yes, I think so.  I think there's still a way to go before we eradicate dengue fever.

Kat::  That was Dr. Frank Jiggins from the University of Cambridge.

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