Dr Physilia Chua, Wellcome Sanger Institute. Image credit: Wellcome Sanger Institute
Innovation in science takes many forms. Be it a tweak that improves technology or a protocol, all the way to the development of new platforms and therapeutics which are the cornerstones of Biotech companies. Translating science at Sanger is about impact, closing the gaps in technologies that will continue to improve health and biodiversity.
Here, at Sanger, we are lucky to be working at the crossroads of innovation and have many role models who are paving the way toward a healthier, more sustainable future. Physilia Chua is one of them. She is a postdoctoral fellow leading the BIOSCAN flying insects project in the UK and her work documents UK insect diversity and the discovery of species interactions.
She is part of the Tree of Life Programme and her team has recently won a Translation Committee Fund from the Technology Translation team at Sanger with the aim of making sequencing more accessible. Her team is working to adapt three existing high-throughput DNA sequencing protocols to an ONT (Oxford Nanopore Technology) platform, which is a small, portable and affordable sequencing machine. This will open the door to sequencing anything, anytime, anywhere.
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First collection plate of insects from BIOSCAN at the Sanger Institute. Image credit: Lyndall Pereira / Wellcome Sanger Institute
In this interview, we spoke to Physilia to understand the project further and her motivation in becoming an innovator. Physilia, how did it all start?
Well, it starts with three words: anything, anytime, anywhere. We are developing simple-to-use instructions for anyone interested in carrying out sequencing for malaria surveillance and biodiversity studies. With our project, anyone, anywhere will be able to sequence locally (almost) in real-time.
The idea came up when talking to Mara Lawniczak, the Principal Investigator on the project. We work with partners all over the world, and we are planning on expanding collaborations. Challenges such as acquiring shipping permits in a timely manner for samples to be sent to Sanger for sequencing are a barrier for partners requiring real-time information. Hence, we need to develop new tools to help partners sequence locally, with their own equipment in the field, and thus become autonomous.
To do this, they need to be able to use Sanger-developed gene panels (an assembly of specific genes that are selected for a specific task, in this case for species identification) but at a local level. How? With ONT devices, which are relatively cheap and portable. We use a range of protocols at Sanger, some of which are high throughput, using an industrial scale set up with expensive machines and requiring significant expertise to run. But technology is advancing fast and now we have ONT MinIONs, which are thumbdrive-sized, portable, and affordable sequencing machines. We are translating our protocols so that they can be used with this technology. This will allow our partners to sequence their own DNA extract in real-time, thus bringing down the barrier to species monitoring locally worldwide.
“Well, it starts with three words: anything, anytime, anywhere... With our project, anyone, anywhere will be able to sequence locally (almost) in real-time.”
So, which are the protocols you are looking into?
We are now working on guides for three protocols that we use here at Sanger: the Pf Amplicon Toolkit, ANOSPP, and BIOSCAN panels. The first set of easy-to-use guides that we’re working on is for the Pf Amplicon toolkit, which detects whether the parasite that causes malaria (Plasmodium falciparum) exhibits any drug resistance. Malaria is a deadly disease in many countries and knowing if a person has been infected with drug-resistant Plasmodium can help save lives. This toolkit will allow public health officials in countries affected by malaria to monitor drug resistance in real-time to make informed targeted treatments.
The second one, the ANOSPP panel, can tell us the species of any mosquito in the Anopheles genus, which is the family of mosquitoes that can transmit malaria, and also indicate if the mosquito might be infected with the Plasmodium parasite. This is vital in the fight against malaria and early detection is key to the successful surveillance of malaria prevalence and transmission.
The first two protocols are part of MalariaGEN, a global data-sharing network to support the effective control of malaria. The third one is the BIOSCAN panel, which will be able to identify insect species and reveal symbiotic interactions between insects and the environment. BIOSCAN is a new initiative launched by the International Barcode of Life (iBOL) to study species diversity and interactions at massive scales globally.
In this interview, we spoke to Physilia to understand the project further and her motivation in becoming an innovator. Physilia, how did it all start?
Well, it starts with three words: anything, anytime, anywhere. We are developing simple-to-use instructions for anyone interested in carrying out sequencing for malaria surveillance and biodiversity studies. With our project, anyone, anywhere will be able to sequence locally (almost) in real-time.
“Well, it starts with three words: anything, anytime, anywhere... With our project, anyone, anywhere will be able to sequence locally (almost) in real-time.”
Dr Physilia Chua
Welllcome Sanger Institute
The idea came up when talking to Mara Lawniczak, the Principal Investigator on the project. We work with partners all over the world, and we are planning on expanding collaborations. Challenges such as acquiring shipping permits in a timely manner for samples to be sent to Sanger for sequencing are a barrier for partners requiring real-time information. Hence, we need to develop new tools to help partners sequence locally, with their own equipment in the field, and thus become autonomous.
To do this, they need to be able to use Sanger-developed gene panels (an assembly of specific genes that are selected for a specific task, in this case for species identification) but at a local level. How? With ONT devices, which are relatively cheap and portable. We use a range of protocols at Sanger, some of which are high throughput, using an industrial scale set up with expensive machines and requiring significant expertise to run. But technology is advancing fast and now we have ONT MinIONs, which are thumbdrive-sized, portable, and affordable sequencing machines. We are translating our protocols so that they can be used with this technology. This will allow our partners to sequence their own DNA extract in real-time, thus bringing down the barrier to species monitoring locally worldwide.
So, which are the protocols you are looking into?
We are now working on guides for three protocols that we use here at Sanger: the Pf Amplicon Toolkit, ANOSPP, and BIOSCAN panels. The first set of easy-to-use guides that we’re working on is for the Pf Amplicon toolkit, which detects whether the parasite that causes malaria (Plasmodium falciparum) exhibits any drug resistance. Malaria is a deadly disease in many countries and knowing if a person has been infected with drug-resistant Plasmodium can help save lives. This toolkit will allow public health officials in countries affected by malaria to monitor drug resistance in real-time to make informed targeted treatments.
The second one, the ANOSPP panel, can tell us the species of any mosquito in the Anopheles genus, which is the family of mosquitoes that can transmit malaria, and also indicate if the mosquito might be infected with the Plasmodium parasite. This is vital in the fight against malaria and early detection is key to the successful surveillance of malaria prevalence and transmission.
The first two protocols are part of MalariaGEN, a global data-sharing network to support the effective control of malaria. The third one is the BIOSCAN panel, which will be able to identify insect species and reveal symbiotic interactions between insects and the environment. BIOSCAN is a new initiative launched by the International Barcode of Life (iBOL) to study species diversity and interactions at massive scales globally.
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BIOSCAN in action in the grounds of the Wellcome Sanger Institute. Image credit: Edel Sheerin / Wellcome Sanger Institute
Tell us more about the third panel - sounds like an exciting new project
It is! The BIOSCAN panel is still in its early stages of development and is currently focused on determining the species of any flying insect. However, the ambition is for it to pick up residues in samples of whatever insects interact with, giving us information about its diet, plant interactions, parasites or microbes. This can tell us plenty of things about the insect and its daily life. If we do this for one million specimens, we can just imagine the impressive atlas of dynamic insect interactions we can get from that. This is important as insects play a huge role in the ecosystem such as pollination and nutrient cycling. With climate change and other external pressures, knowing how insects interact and adapt to their environment is key to our wellbeing - especially since we rely on them to ensure that cocoa flowers are pollinated, for instance. Imagine a world without chocolates! I for one would be rather miserable.
Now, as I said, the project depends very much on external partners supplying samples for us to sequence. At present, our partners are all in the UK and this reduces the challenges of international sample shipping. However, thinking ahead to the future when we might want to expand this BIOSCAN project to incorporate samples from other international partners, getting samples to us can be quite tricky and take a long time. To overcome this, we need to ensure that partners can have access to their own on-site sequencer.
“The ambition is for [BIOSCAN] to pick up residues in samples of whatever insects interact with, giving us information about its diet, plant interactions, parasites or microbes. This can tell us plenty about the insect and its daily life.”
There is a need to translate these Sanger protocols to make them accessible
That’s right! These high throughput protocols have not been translated yet. What happens at the moment is very top-down. The partners send us the samples, we sequence them here, at Sanger, and we analyse the data. We then get back to them and let them know the results. This obviously takes a long time, sometimes up to a year.
Now, whilst it’s great that our high-throughput sequencing can analyse a lot of samples at the same time, this, in turn, is also an issue. In some countries in Africa or Asia where malaria infections have decreased, you might only get two or three samples. Still, you need to sequence them to keep track of the disease. With so few, gathering enough samples to bring down the costs of high-throughput sequencing could take months. We need to give partners a way to sequence one or two samples at a low cost immediately.
Tell us more about the third panel - sounds like an exciting new project
It is! The BIOSCAN panel is still in its early stages of development and is currently focused on determining the species of any flying insect. However, the ambition is for it to pick up residues in samples of whatever insects interact with, giving us information about its diet, plant interactions, parasites or microbes. This can tell us plenty of things about the insect and its daily life. If we do this for one million specimens, we can just imagine the impressive atlas of dynamic insect interactions we can get from that. This is important as insects play a huge role in the ecosystem such as pollination and nutrient cycling. With climate change and other external pressures, knowing how insects interact and adapt to their environment is key to our wellbeing - especially since we rely on them to ensure that cocoa flowers are pollinated, for instance. Imagine a world without chocolates! I for one would be rather miserable.
Now, as I said, the project depends very much on external partners supplying samples for us to sequence. At present, our partners are all in the UK and this reduces the challenges of international sample shipping. However, thinking ahead to the future when we might want to expand this BIOSCAN project to incorporate samples from other international partners, getting samples to us can be quite tricky and take a long time. To overcome this, we need to ensure that partners can have access to their own on-site sequencer.
“The ambition is for [BIOSCAN] to pick up residues in samples of whatever insects interact with, giving us information about its diet, plant interactions, parasites or microbes. This can tell us plenty about the insect and its daily life.”
Dr Physilia Chua
Welllcome Sanger Institute
There is a need to translate these Sanger protocols to make them accessible
That’s right! These high throughput protocols have not been translated yet. What happens at the moment is very top-down. The partners send us the samples, we sequence them here, at Sanger, and we analyse the data. We then get back to them and let them know the results. This obviously takes a long time, sometimes up to a year.
Now, whilst it’s great that our high-throughput sequencing can analyse a lot of samples at the same time, this, in turn, is also an issue. In some countries in Africa or Asia where malaria infections have decreased, you might only get two or three samples. Still, you need to sequence them to keep track of the disease. With so few, gathering enough samples to bring down the costs of high-throughput sequencing could take months. We need to give partners a way to sequence one or two samples at a low cost immediately.
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Malaise trap collecting insects. Image credit: Luke Lythgoe / Wellcome Sanger Institute
What will your partners be able to do that they can't do now?
Many things. Imagine for instance, that a partner is interested in an insect which is specific to their country or area, a native species for example. They would be able to catch it, extract the DNA, and understand what the insect has interacted with immediately. MinION sequencing is rapid, taking one or two days at most, meaning that they get almost instant answers, instead of waiting months. This is especially significant with malaria surveillance. Once a research lab detects a malaria infection, being able to sequence the samples themselves in real-time will allow them to react quicker: they’ll know the malaria strain the person is infected with (there are different types) and thus will be able to advise the drugs needed. Depending on the strain, some drugs work better than others.
This means that our work can also help with drug development, targeting specific Plasmodium parasites and malaria strains. Even though the MinION sequencer is affordable, training is required to properly use the equipment. Therefore, we expect our easy-to-use guides will help make a massive difference in reducing the training time and costs required.
“Imagine... that a partner is interested in an insect which is specific to their country or area... They would be able to catch it, extract the DNA, and understand what the insect has interacted with immediately.”
What has made it possible for you at Sanger to deliver this innovation?
Well, the Translation Committee Fund has been a game changer. We are now able to hire someone who is able to accelerate the project. Without it, it would’ve relied on us and we’re already heavily invested in different projects.
The BIOSCAN project is in a preliminary phase, and already has seven partners. With this technology, we hope to be able to attract more partners. We’ve already shared this idea with some of them and they are very keen to see it in action. Therefore, the ability to hire someone to help push this along is vital for the project.
What will your partners be able to do that they can't do now?
Many things. Imagine for instance, that a partner is interested in an insect which is specific to their country or area, a native species for example. They would be able to catch it, extract the DNA, and understand what the insect has interacted with immediately. MinION sequencing is rapid, taking one or two days at most, meaning that they get almost instant answers, instead of waiting months. This is especially significant with malaria surveillance. Once a research lab detects a malaria infection, being able to sequence the samples themselves in real-time will allow them to react quicker: they’ll know the malaria strain the person is infected with (there are different types) and thus will be able to advise the drugs needed. Depending on the strain, some drugs work better than others.
“Imagine... that a partner is interested in an insect which is specific to their country or area... They would be able to catch it, extract the DNA, and understand what the insect has interacted with immediately.”
Dr Physilia Chua
Welllcome Sanger Institute
This means that our work can also help with drug development, targeting specific Plasmodium parasites and malaria strains. Even though the MinION sequencer is affordable, training is required to properly use the equipment. Therefore, we expect our easy-to-use guides will help make a massive difference in reducing the training time and costs required.
What has made it possible for you at Sanger to deliver this innovation?
Well, the Translation Committee Fund has been a game changer. We are now able to hire someone who is able to accelerate the project. Without it, it would’ve relied on us and we’re already heavily invested in different projects.
The BIOSCAN project is in a preliminary phase, and already has seven partners. With this technology, we hope to be able to attract more partners. We’ve already shared this idea with some of them and they are very keen to see it in action. Therefore, the ability to hire someone to help push this along is vital for the project.
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Malaise trap at Carrifran. Image Credit: Lyndall Pereira / Wellcome Sanger Institute
What skills would you say are important to be innovative and entrepreneurial in science?
I think it's not exactly a skill, I think it's the ability to dream bigger - how can you apply your research to real-world problems? It's not about making something commercially viable because this is not a commercial product. We don't make money out of this. But it's a way for us to make things easier for global collaboration in genomics. We’re targeting our partners for now, but the next stage would maybe be citizen scientists, for example.
Our ultimate aim is to make science accessible to everyone and make science open. We talk a lot about open science, and Sanger is a great advocate for this, but just advocating and actually doing something about it are two very different things. This is our way of actually doing something about it.
“Our ultimate aim is to make science accessible to everyone and make science open.”
What skills would you say are important to be innovative and entrepreneurial in science?
I think it's not exactly a skill, I think it's the ability to dream bigger - how can you apply your research to real-world problems? It's not about making something commercially viable because this is not a commercial product. We don't make money out of this. But it's a way for us to make things easier for global collaboration in genomics. We’re targeting our partners for now, but the next stage would maybe be citizen scientists, for example.
Our ultimate aim is to make science accessible to everyone and make science open. We talk a lot about open science, and Sanger is a great advocate for this, but just advocating and actually doing something about it are two very different things. This is our way of actually doing something about it.
“Our ultimate aim is to make science accessible to everyone and make science open.”
Dr Physilia Chua
Welllcome Sanger Institute
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Physilia Chua using the Sanger Institute's analytics software to deliver BIOSCAN and ANOSPP. Image credit: Wellcome Sanger Institute
