Dr Qianxin Wu, Wellcome Sanger Institute. Image credit: Wellcome Sanger Institute
In this second part of our innovator blog series, we spoke to Qianxin Wu, a Staff Scientist at the Wellcome Sanger Institute who works jointly between the Cellular Genetics research programme and the Cellular and Gene Editing R&D team. Qianxin is at the forefront of innovation, working on CRISPR, genome editing and single-cell technologies, amongst other things. She is a highly entrepreneurial scientist, with a passion for problem solving.
Innovation takes many forms – from a tweak that improves technology, all the way to the development of new medicines. Translating science is about adapting research, moving research beyond the lab, or closing gaps in technologies, so that it can be used to improve our lives. Qianxin spoke to us about spotting those opportunities, and getting her projects going.
Qianxin, what does it take to be an innovator?
I think you do need to be curious to be innovative, and also imaginative. I have a love for solving problems and I am currently working on three very exciting projects in which I am doing just that. The first one is a personalised CRISPR library, which we hope will be a significant step towards refining drug discovery in a personalised way. The second one is a point-of-care technology for the detection of viral pathogens, which is called INSIGHT. The third project, which has just started, is a collaboration with an industry partner, Acxel, in which I am developing molecular reagents to link DNA sequence to function in single cells. Most current solutions for doing this are time-consuming, often costly, are can’t be applied to single cells.
Curiously, I started working on more translational projects towards the beginning of the pandemic, when I changed my job role. And a new joint position between two departments at Sanger has now allowed me to do this type of translational work. But I must say, I never thought of myself as entrepreneurial. It was really just… a problem came out and I thought, well it’d be good to have a solution!
“I must say, I never thought of myself as entrepreneurial. It was really just… a problem came out and I thought, well it’d be good to have a solution!”
Qianxin, what does it take to be an innovator?
I think you do need to be curious to be innovative, and also imaginative. I have a love for solving problems and I am currently working on three very exciting projects in which I am doing just that. The first one is a personalised CRISPR library, which we hope will be a significant step towards refining drug discovery in a personalised way. The second one, is a point-of-care technology for the detection of viral pathogens, which is called INSIGHT. The third project, which has just started, is a collaboration with an industry partner, Acxel, in which I am developing molecular reagents to link DNA sequence to function in single cells. Most current solutions for doing this are time-consuming, often costly, are can’t be applied to single cells.
“I must say, I never thought of myself as entrepreneurial. It was really just… a problem came out and I thought, well it’d be good to have a solution!”
Dr Qianxin Wu
Welllcome Sanger Institute
Curiously, I started working on more translational projects towards the beginning of the pandemic, when I changed my job role. And a new joint position between two departments at Sanger has now allowed me to do this type of translational work. But I must say, I never thought of myself as entrepreneurial. It was really just… a problem came out and I thought, well it’d be good to have a solution!
qianxin_blog_lab_800
Qianxin working in her laboratory at the Wellcome Sanger Institute
INSIGHT, the technology for the detection of viral pathogens seems quite timely, can you tell us more about this?
It is a testing strategy for viral pathogens, including COVID-19, from saliva or throat/nasal swabs using a point-of-care test, which is a test that could be conducted at a patient’s residence. Currently researchers from the Department of Engineering and University of Cambridge are developing a portable point-of-care device for the INSIGHT technology and the research is also available for anyone else to use and take forward.
I conceived it around February 2020, right at the start of the pandemic, which is when I joined a meeting at the Royal Society. I think at that time, we had just a few cases of COVID-19 in the UK. At the Royal Society gathering, we could all more or less envision what was about to happen.
My first thought was that, actually, the only way to control a possible pandemic would be to carry out population-wide testing. But how to manage it with a whole country? It wasn’t possible just to screen the whole population, we needed something that could ideally be used at home. If we could develop something simple and accurate, we might actually help with the pandemic. Our primary idea had been to create a decentralised point-of-care testing that would work along with centralised testing. In this way, the sample wouldn’t have to then be analysed at a lab but could give a result instantly. That was when INSIGHT was conceived. It was a very interesting journey even though it hasn't been deployed for COVID-19, it has the potential to be used in the detection of other pathogens moving forward.
Of course, I didn’t do it alone, I was very lucky to meet a brilliant clinical PhD fellow at Sarah Teichmann's lab, Chenqu Suo. We worked on it together for three to four months, and suddenly we had it! Once the technology was ready we spoke to the Technology Translation team at Sanger and we patented it and also published it as soon as we could so that other people could use it too.
INSIGHT, the technology for the detection of viral pathogens seems quite timely, can you tell us more about this?
It is a testing strategy for viral pathogens, including COVID-19, from saliva or throat/nasal swabs using a point-of-care test, which is a test that could be conducted at a patient’s residence. Currently researchers from the Department of Engineering and University of Cambridge are developing a portable point-of-care device for the INSIGHT technology and the research is also available for anyone else to use and take forward.
I conceived it around February 2020, right at the start of the pandemic, which is when I joined a meeting at the Royal Society. I think at that time, we had just a few cases of COVID-19 in the UK. At the Royal Society gathering, we could all more or less envision what was about to happen.
My first thought was that, actually, the only way to control a possible pandemic would be to carry out population-wide testing. But how to manage it with a whole country? It wasn’t possible just to screen the whole population, we needed something that could ideally be used at home. If we could develop something simple and accurate, we might actually help with the pandemic. Our primary idea had been to create a decentralised point-of-care testing that would work along with centralised testing. In this way, the sample wouldn’t have to then be analysed at a lab but could give a result instantly. That was when INSIGHT was conceived. It was a very interesting journey even though it hasn't been deployed for COVID-19, it has the potential to be used in the detection of other pathogens moving forward.
Of course, I didn’t do it alone, I was very lucky to meet a brilliant clinical PhD fellow at Sarah Teichmann's lab, Chenqu Suo. We worked on it together for three to four months, and suddenly we had it! Once the technology was ready we spoke to the Technology Translation team at Sanger and we patented it and also published it as soon as we could so that other people could use it too.
You are working on other projects such as the personalised CRISPR libraries you mentioned earlier - what is the challenge you are trying to solve there?
That's a very different thing. Let’s start with the basics - what is a CRISPR library? In general terms, it’s a set of genes that have been purposely modified to be able to study a certain condition, such as cystic fibrosis or any other genetically driven disease. These are useful when studying the responses of cells to different drugs, for example. Most of these CRISPR libraries target coding regions present in a genome. That is the DNA or RNA that encode proteins, which are important building blocks for cells as well as the functional work-horses of the body. Proteins will essentially determine how different cell types work and what they look like.
So, we have a good number of these coding region CRISPR libraries. What we don’t have many of are libraries based in non-coding regions. Not only are they difficult to generate chemically, but are expensive and labour-intensive to develop.
Why are they important? We are starting to understand the role of non-coding genes in our genome. These are the genes that do not seem to have a direct function in what our cells look like. However, they do have other functions, which we are now starting to decipher, such as controlling the activity of protein-coding genes. They help determine which genes are turned on or off, and when. Other non-coding regions may be important for protein assembly, which is how the building blocks in our body are created.
Hence, my proposal was: Could we actually develop a library that targets both coding and the important non-coding region at the same time? And, can they be tailored to different people and to different cell types?
Why? Because for different people with different cell types, there will be variations in the DNA or RNA. The question posed here is, can we have a personalised or cell-specific library targeting both the coding and non-coding parts of the genome? That’s the problem that we’re interested in solving at the moment.
This all started in a conversation with another researcher, now an ex-colleague, Junjing Wu, who studies the function of Single Nucleotide Polymorphisms (SNPs) in genes - the substitutions of single letters in our genetic code. Now you see, SNPs are, essentially, the most common type of genetic variation in humans and they tend to be found in the non-coding regions of the genome. Most of the variations don’t seem to have any apparent effect. However, occasionally, these small variations have important implications in the study of human health. For example, a particular SNP can increase susceptibility to environmental factors that cause cancer, or increase the risk of developing diseases such as diabetes. Junjing found so many different streams in her research, she was looking for a way in which we could somehow screen for the SNPs’ function as well when using CRISPR libraries.
It’s a really exciting project and it has been able to progress with a Translation Committee fund, which is Sanger’s translational grant. I was originally looking for funding within academia but then realised that there was funding for this within a more entrepreneurial setting, which is when I contacted the Technology Translation team. With the fund we have been able to hire a postdoc to move the project forward.
Along with the postdoc, we then brought this idea to the Wellcome Genome Campus Startup School as a project. The Startup School helped us to think about the market - who’d be the customer of the technology. From a research point of view, we can see the value, but at the Startup school, we were pushed to think with a commercial hat on.
It helped us get to the conclusion that if we can generate a very good quality library, it will change the current way we’re testing for CRISPR screening because we wouldn't have to use a universal library. Instead, we’ll have a library that tailors to the particular cell we're looking at, or the particular person. This would allow researchers to get far more information out from the CRISPR screen as it is personalised and, importantly, targets a region which we are currently ignoring: the non-coding genome. To put it into context: it’d be a step towards personalised medicine in genomics as we’d be making sure that we’d be testing new drugs taking into account the particularities of each person’s own genome.
“I was originally looking for funding within academia but then realised that there was funding for this within a more entrepreneurial setting, which is when I contacted the Technology Translation team. With the fund we have been able to hire a postdoc to move the project forward.”
You are working on other projects such as the personalised CRISPR libraries you mentioned earlier - what is the challenge you are trying to solve there?
That's a very different thing. Let’s start with the basics - what is a CRISPR library? In general terms, it’s a set of genes that have been purposely modified to be able to study a certain condition, such as cystic fibrosis or any other genetically driven disease. These are useful when studying the responses of cells to different drugs, for example. Most of these CRISPR libraries target coding regions present in a genome. That is the DNA or RNA that encode proteins, which are important building blocks for cells as well as the functional work-horses of the body. Proteins will essentially determine how different cell types work and what they look like.
So, we have a good number of these coding region CRISPR libraries. What we don’t have many of are libraries based in non-coding regions. Not only are they difficult to generate chemically, but are expensive and labour-intensive to develop.
Why are they important? We are starting to understand the role of non-coding genes in our genome. These are the genes that do not seem to have a direct function in what our cells look like. However, they do have other functions, which we are now starting to decipher, such as controlling the activity of protein-coding genes. They help determine which genes are turned on or off, and when. Other non-coding regions may be important for protein assembly, which is how the building blocks in our body are created.
Hence, my proposal was: Could we actually develop a library that targets both coding and the important non-coding region at the same time? And, can they be tailored to different people and to different cell types?
Why? Because for different people with different cell types, there will be variations in the DNA or RNA. The question posed here is, can we have a personalised or cell-specific library targeting both the coding and non-coding parts of the genome? That’s the problem that we’re interested in solving at the moment.
This all started in a conversation with another researcher, now an ex-colleague, Junjing Wu, who studies the function of Single Nucleotide Polymorphisms (SNPs) in genes - the substitutions of single letters in our genetic code. Now you see, SNPs are, essentially, the most common type of genetic variation in humans and they tend to be found in the non-coding regions of the genome. Most of the variations don’t seem to have any apparent effect. However, occasionally, these small variations have important implications in the study of human health. For example, a particular SNP can increase susceptibility to environmental factors that cause cancer, or increase the risk of developing diseases such as diabetes. Junjing found so many different streams in her research, she was looking for a way in which we could somehow screen for the SNPs’ function as well when using CRISPR libraries.
“I was originally looking for funding within academia but then realised that there was funding for this within a more entrepreneurial setting, which is when I contacted the Technology Translation team. With the fund we have been able to hire a postdoc to move the project forward.”
Dr Qianxin Wu
Welllcome Sanger Institute
It’s a really exciting project and it has been able to progress with a Translation Committee fund, which is Sanger’s translational grant. I was originally looking for funding within academia but then realised that there was funding for this within a more entrepreneurial setting, which is when I contacted the Technology Translation team. With the fund we have been able to hire a postdoc to move the project forward.
Along with the postdoc, we then brought this idea to the Wellcome Genome Campus Startup School as a project. The Startup School helped us to think about the market - who’d be the customer of the technology. From a research point of view, we can see the value, but at the Startup school, we were pushed to think with a commercial hat on.
It helped us get to the conclusion that if we can generate a very good quality library, it will change the current way we’re testing for CRISPR screening because we wouldn't have to use a universal library. Instead, we’ll have a library that tailors to the particular cell we're looking at, or the particular person. This would allow researchers to get far more information out from the CRISPR screen as it is personalised and, importantly, targets a region which we are currently ignoring: the non-coding genome. To put it into context: it’d be a step towards personalised medicine in genomics as we’d be making sure that we’d be testing new drugs taking into account the particularities of each person’s own genome.
Now you have a collaboration with a spin out company from the University of Cambridge. Can you tell us what it is about?
Before enrolling in the Startup School at the Wellcome Genome Campus, I attended another entrepreneur course, called EnterpriseTech, and I met some people there. They are a group of engineers who’d just created a company, Acxel, a spinout from the University of Cambridge. They had developed an instrument that could manipulate and move very small liquid droplets using electricity.
We started to talk and I said to them: Now is the age of gene editing, we’re probably going to understand the whole function of the gene base by base in the next few decades. I am convinced that the future is single-cell genomics, which is the study of the individuality of cells using a genome and phenome-wide approach. Not only looking at one of its aspects, but its structure, function, and dynamics as a whole.
Therefore, this machine should be able to carry out single-cell genomics experiments if they wanted it to be viable, as this is a growing field. We continued meeting and chatting and it all crystalised in a collaboration with Sanger. At the Institute, we are developing a single cell-based molecular reagents whilst they're further developing their machine to accommodate this. And the idea is, if everything works out, it could be combined as a product for genetic research.
It is all very exciting! They have delivered their prototype machine to our lab, which we will start using soon. It’s great that we are able to explore new technologies, without which we might not be able to do new things in this way. Sarah Teichmann’s support was crucial for this too - there was no space or equipment for this, but she was able to provide the help needed; without her and Andrew Bassett’s input, this just wouldn't have happened. Collaborations of this nature need to be supported. We need the resources, the backing of our management teams, and the ability to try them out. In this sense, Sarah Teichmann and Andrew Bassett were huge enablers of the project.
“It all crystalised in a collaboration with Sanger... we are developing a single cell-based molecular reagents whilst they're further developing their machine to accommodate this... if everything works out, it could be combined as a product for genetic research.”
Now you have a collaboration with a spin out company from the University of Cambridge. Can you tell us what it is about?
Before enrolling in the Startup School at the Wellcome Genome Campus, I attended another entrepreneur course, called EnterpriseTech, and I met some people there. They are a group of engineers who’d just created a company, Acxel, a spinout from the University of Cambridge. They had developed an instrument that could manipulate and move very small liquid droplets using electricity.
We started to talk and I said to them: Now is the age of gene editing, we’re probably going to understand the whole function of the gene base by base in the next few decades. I am convinced that the future is single-cell genomics, which is the study of the individuality of cells using a genome and phenome-wide approach. Not only looking at one of its aspects, but its structure, function, and dynamics as a whole.
“It all crystalised in a collaboration with Sanger... we are developing a single cell-based molecular reagents whilst they're further developing their machine to accommodate this... if everything works out, it could be combined as a product for genetic research.”
Dr Qianxin Wu
Welllcome Sanger Institute
Therefore, this machine should be able to carry out single-cell genomics experiments if they wanted it to be viable, as this is a growing field. We continued meeting and chatting and it all crystalised in a collaboration with Sanger. At the Institute, we are developing a single cell-based molecular reagents whilst they're further developing their machine to accommodate this. And the idea is, if everything works out, it could be combined as a product for genetic research.
It is all very exciting! They have delivered their prototype machine to our lab, which we will start using soon. It’s great that we are able to explore new technologies, without which we might not be able to do new things in this way. Sarah Teichmann’s support was crucial for this too - there was no space or equipment for this, but she was able to provide the help needed; without her and Andrew Bassett’s input, this just wouldn't have happened. Collaborations of this nature need to be supported. We need the resources, the backing of our management teams, and the ability to try them out. In this sense, Sarah Teichmann and Andrew Bassett were huge enablers of the project.
It seems like you're very much driven by challenges. Would you say that?
That's probably true. If there’s a question, it’s interesting to find a technological solution for it. You need some degree of curiosity to be innovative. You have to spot the possible solutions instead of focusing on the problem. You’re not too small or inexperienced to solve it, you might just need to learn a little more. I also think you need to have some degree of imagination - it allows you to conceive new ways of doing things. There are lots of things which might not happen, but if you don't have the imagination, then they definitely won’t.
When I now look back, there were two key factors that made these projects happen. One was the number of interactions I’ve actively sought, which have fueled these collaborations. The other is effort. For each project, the scientific and personal toll was immense, especially to get started. I’ve had to think: How am I going to make this happen? If I hadn’t, then the idea would’ve just stayed on a piece of paper.
It seems like you're very much driven by challenges. Would you say that?
That's probably true. If there’s a question, it’s interesting to find a technological solution for it. You need some degree of curiosity to be innovative. You have to spot the possible solutions instead of focusing on the problem. You’re not too small or inexperienced to solve it, you might just need to learn a little more. I also think you need to have some degree of imagination - it allows you to conceive new ways of doing things. There are lots of things which might not happen, but if you don't have the imagination, then they definitely won’t.
“There were two key factors that made these projects happen. One was the number of interactions I’ve actively sought... the other is effort.”
Dr Qianxin Wu
Welllcome Sanger Institute
When I now look back, there were two key factors that made these projects happen. One was the number of interactions I’ve actively sought, which have fueled these collaborations. The other is effort. For each project, the scientific and personal toll was immense, especially to get started. I’ve had to think: How am I going to make this happen? If I hadn’t, then the idea would’ve just stayed on a piece of paper.
