Q&A: Behind the scenes of Imperial's mosquito labs

Lee Phillimore at work at Target Malaria's Crisanti Lab

Lee Phillimore, a research technician in the Crisanti Lab, reveals the work behind rearing mosquitos for malaria research.

Over 600,000 people die per year from malaria – most of whom are young children in sub-Saharan Africa. Scientists in Imperial are innovating new ways to tackle this disease, which is carried by female Anopheles mosquitoes. 

Around 50 members of staff in the Sir Alexander Fleming Building in Imperial's South Kensington campus work in mosquito labs, rearing and researching mosquitos for novel methods of controlling vector-borne diseases.

We speak to Lee Phillimore, a research technician at the Crisanti Lab, about the technical challenges he encounters in his work at the insectary.

Q: Can you tell us about what you do at Imperial?

A: I'm a research technician in the Crisanti lab, and my work mainly involves working in the insectary with genetically modified mosquitoes. Anopheles mosquitoes are the vectors for malaria, a disease which kills a child every minute in Africa. We work as part of Target Malaria, which is an international not-for-profit research consortium that's dedicated to helping end malaria.

We are specifically working on a technology called gene drive that biases the natural laws of inheritance by causing a selected genetic trait to spread rapidly through a species via sexual reproduction over several generations. Gene drive works by increasing the likelihood that a modified gene will be inherited by its offspring. Normally, genes have a 50/50 chance of being inherited, gene drive systems could increase the chance of upwards of 99 per cent.

We’re trying to develop a gene drive to be used as a vector control tool to help reduce populations of malaria mosquitoes in sub-Saharan Africa, where 96% of deaths and 95% cases of malaria are concentrated (WHO). There are over 850 species of mosquito in Africa, and Target Malaria is focused on the three closely-related species that are the main vectors of malaria: Anopheles gambiae, Anopheles coluzzii and Anopheles arabiensis.

There are several projects ongoing in the lab, but I specifically work with gene drive mosquitoes that could potentially be released in the future to mate with the wild mosquitos, and then gradually over time, reduce the population’s fertility and ideally suppress the wild population.

Q: What does your day-to-day look like?

A: I look after about a dozen different genetically modified mosquito strains. Each strain has to be looked after individually. In the insectary, we have cubicles that are maintained at a certain humidity and temperature because, obviously, South Kensington doesn’t have the ideal breeding conditions for African mosquitoes.

The mosquitoes have a three-week long life cycle that starts from the point of when the eggs are laid, all throughout the four different stages of larvae, to when they become pupae and finally when they emerge as adult mosquitoes. A good chunk of my job involves rearing the mosquitoes throughout their life cycle. 

The females need to drink blood in order to lay eggs, which they lay in dishes of water. We have a machine called a Hemotek, which allows us to take bovine blood, that we get from slaughterhouses, and warm it up to body temperature. The warmed blood is placed into a dish with a membrane at the top of the cage. You can see the adult female come up to drink the blood and after a few days, they are able to lay eggs.

The males can just subsist on sugar water, which the females also need, and we feed them via bottles with filter paper poking out of the top. 

We keep the eggs in trays of water and when they hatch and become larvae, we feed them little pellets of food. If you know koi carp food, like what you would use in your pond at home, and we just put a pellet of this in every day to give them nutrition.

You see them grow bigger and bigger from tiny little larvae.

They stop feeding when they curl up into pupae, but they can still swim around. The pupae stage is when you can actually determine the sex of the mosquito.

We look at the pupae under a microscope and create new cages with around 50 males and 50 females. After about 24 hours, they emerge as adult mosquitoes and we have a brand-new cage of the next generation of mosquitoes.

Q: How does rearing these mosquitoes allow you to experiment with different genetically modified strains?

A: For many of my lines, the genetically modified strains carry a fluorescent marker that denote that they've inherited the transgene of interest, and so you can track that it is inherited from generation to generation.

By maintaining separate trays and cages we are able to keep multiple genetically modified strains in the same cubicle without risk of cross-contamination. 

... [M]y specific project looks at gene drives that affect the reproductivity of female mosquitos. Lee Phillimore Target Malaria

For experiments, my specific project looks at gene drives that affect the reproductivity of female mosquitos. For instance, make them unable to reproduce, unable to suck blood or unable to lay eggs.

The idea being that over time, after release more and more mosquitoes with our gene drive would spread through the wild and pass on less and less reproductive capabilities. 

Q: What are the challenges in rearing mosquitoes?

A: Mosquitoes are very particular. If they go a day in the cage without sugar water, for example, they could all just drop dead. If it’s a line that’s being kept in that cage and there alone, that’s just years of work gone because someone forgot to replace the sugar in a bottle.

There’s also a problem that if there’s too many larvae in one tray, then they grow at a slower rate, or they may even start eating each other. There are also microsporidia, a kind of fungal parasite, that could affect the health of the strain so we have to continually ensure cleanliness. We bleach the eggs to prevent the spread of anything like this. 

These challenges are of course in addition to having to be maintained in conditions more akin to sub-Saharan Africa or a tropical rainforest... Lee Phillimore Target Malaria

These challenges are of course in addition to having to be maintained in conditions more akin to sub-Saharan Africa or a tropical rainforest than that of a lab a couple of streets down from Hyde Park.

There are practical aspects like these that need to be looked after and looked after properly. 

Q: How did you get into this line of work?

I guess I do have a link with malaria. I’m half Malaysian-Chinese, so going to Malaysia as a kid, you’re always aware of the spectre of mosquitoes, though the concern is more about dengue in that part of the world at the moment. 

My academic background is actually nothing to do with mosquitoes. I have a Bachelors in Biochemistry and my Master’s is in Neuroscience. I previously worked in neuroscience labs with Drosophila (fruit flies).

I enjoyed working with insects and I wanted to learn new, exciting techniques and technologies. The Target Malaria lab (Crisanti lab) is at the forefront, so it’s been fantastic to work here. 

But mosquitoes are very different from what I was used to. They’re much more picky than Drosophila. For Drosophila, you can maintain them just by giving them new food once a month, but with mosquitoes, you have to be checking them continually every day. 

I’ve been asked many times whether I get bitten, and yes, of course I get bitten. Lee Phillimore Target Malaria

I’ve been asked many times whether I get bitten, and yes, of course I get bitten. Our lab does not maintain any malaria mosquitoes and does not work with the parasite so there is not risk of getting malaria. But you can’t stop a few free flyers from getting loose from the cages so we’re very careful about preventing them from being released into the wild.

At the entrance to the insectary, there are two doors. At each door, there's an air conditioner that blows air downwards that you need to stand under for 10 seconds before you can go out. It blows everything off your clothes to ensure nothing ever escapes.

But yes, I do get the occasional bite.

Q: Have you ever had to consider the ethical aspects of designing gene drives?

A: I was at the Great Exhibition Road Festival last year and I was talking to members of the public on behalf of the lab. Many people asked me about ethical issues, like, “Is it ethical to release something into the world with the intention of killing a species off?”

I mostly answer that there are over 3500 species of mosquitoes on the planet, and very, very few of them can actually carry the malarial parasite.

So, we’re not trying to eradicate all mosquitoes on the planet – just looking to reduce the population of those that carry malaria.

We are trying to create gene drives that reduce a mosquito’s reproductivity but can spread throughout a wild population, whilst combating issues such as potential resistance or other undesirable consequences.

It’s a continuous process of refinement. It’ll take many years from now to successfully release a gene drive into the wild. There’s a lot of work to be done. 

You don’t have to look hard to find the appalling impact that malaria has in many countries, particularly those considered as poor and developing. Half a million people are killed by malaria each year, mostly African children under the age five and pregnant women. The familial and economic devastation as a result of this disease is staggering.

To be even a small part in the fight against such an awful disease is enough to convince me that my work is worthwhile. Lee Phillimore Target Malaria

To be even a small part in the fight against such an awful disease is enough to convince me that my work is worthwhile.

I consider myself lucky to be able to work hands-on with the mosquitoes and see first-hand the potential impact our genetic tools could have in the future.