Louisa Zoliewski: From chubby mice to everyday toxins
Image courtesy of Louisa Zoliewski
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There are many roads into a genetics career, and so many ways to be a geneticist. Our final guest today is yet another example of someone making great science happen outside of a solely academic role.
In 2022, Dr Louisa Zolkiewski was awarded the inaugural Bruce Cattanach prize from the Genetics Society for an outstanding PhD thesis related to the use of non-human in vivo animal models. Following her PhD, Louisa decided to apply her skills and genetics knowledge in an industry position, working in genetic toxicology.
Louisa: So genetic toxicology is looking at substances and drugs and compounds going to market and seeing whether or not they are safe at a genetic level. So are they toxic to your DNA and your cells in the body, are they safe, does something increase your risk of getting mutations that might then lead to cancer?
Sally: So it's not drugs that are specific to genetic conditions, it's any drug?
Louisa: No, any drug. It could be things like plastics in packagings, or it could be things like chemicals that they use in agriculture, so kind of things like pesticides and herbicides. And if that's going on your food, is that then safe? Food additives or things that are quite common at the moment that people might be looking at whether they're safe or not are kind of like herbal supplements and that sort of thing. So anything and everything can be potentially toxic, I suppose, so we're kind of testing these.
Sally: So you're working within industry at the moment. Are you working for one of the big massive companies or are you working for a small company?
Louisa: Working for a small company. So it's called a CRO, so it's a Contract Research Organisation.
Louisa: So we work on a client basis, so we have clients that come to us with a product and they want it tested. We do the testing and then we send back the results to them and we kind of discuss what it means and help them prepare it and get it ready to submit to people like the FDA and the UK government who then make the final decision to say whether something is safe or not.
Sally: Because one of the things I always heard from people when I was doing my PhD - oh should I go into industry, should I continue in academia - particularly if they're going into these big companies, is: you're such a tiny cog within this massive chain that you're almost like a machine, you're doing the same task day in, day out, but it sounds like what you're doing is quite varied.
Louisa: Yes, and I think because it's a contract research organisation, it is on the smaller side, I think that very much helps. It's partly why I chose to go into a smaller company rather than a bigger company because I've heard exactly the same thing. You get lost in the system and you know, you kind of want to be left to your own devices a little bit. Having done a PhD, you kind of feel like, to some extent, you know what you're doing and you know that if someone gives you a task, you can go away and do it. But equally, you don't want to be so lost that if you want help or you want to talk to someone, you can't.
Sally: And what is the structure like, who are you working with? Do you have lab groups that are all working on the same problem? I have no idea what it looks like.
Louisa: Yeah, so we've got several different lab groups so we, generally speaking, work as a team based on one assay. So day to day I kind of work with the same group of eight people.
Louisa: We do in vivo testing, so we're looking at kind of the late stage testing where companies may have had a couple of tests done in bacteria and in cells, and it might not be quite obvious what's going on. So they then move into a model system that's more similar to humans. And we're trying to get a better understanding of whether or not the genetic mutations are actually occurring, and if they are occurring, does that actually mean that the mutations are happening at a much higher rate than you would expect and are therefore potentially harmful.
Sally: Does working in industry match up to your expectations and preconceptions that you had before you joined?
Louisa: Yes and no, I think. Yes in that there is a lot more freedom day to day to plan your work, you know, you're not working by yourself. So there's a whole team of people working towards one common goal, which is really nice. You don't feel isolated in the same way that you do in your PhD.
Louisa: In terms of no, it's a lot more structured I think than I realised, certainly in this industry and the kind of toxicology testing and safety. It's very, very rigid and getting used to a very different way of working is what I'd say I hadn't realised how much of a difference in way of working it was going to be.
Sally: You mentioned your PhD, so you actually won an award, a Bruce Cattanach prize for best PhD thesis on non-human model organisms. What was your thesis on and what was your non-human model organism?
Louisa: So the non-human model organism was mouse. My PhD was looking at common DNA variations which are associated with our fat distribution and our body shape. So when people talk about being "apple shaped" or "pear shaped", being "apple shaped" is generally considered to be associated with a higher risk for having things like type 2 diabetes and heart disease. And actually in some cases, you know, even things like cancer, you have a slightly increased risk if you carry more of your fat around your kind of abdominal area and around your organs.
Louisa: So we were very much looking at Genome Wide Association Study data, so it's sort of like a survey. They look at whether you've got type 2 diabetes or heart conditions or it can be any disease. They measure things like your height, your weight, your BMI, they collect loads of base information, whether you smoke, whether you don't smoke. And what they then do is a Genome Wide Association Study where they correlate your DNA code with your kind of outward phenotype, so what you look like, what you weigh, whether you smoke, whether you don't smoke, what sort of diseases you might have... And then they combine it and say, well, these specific codes of DNA in this region, in this gene are significantly associated with this outcome.
Louisa: I mean typically in a Genome Wide Association Study, you might have hundreds of thousands of potential DNA variations that are associated with an outcome. So for my project, we were looking at a region of DNA that was called the TBX15/WARS2 locus. So it's got three genes in it.
Sally: Oh, so snappy!
Louisa: I love it! It's got three genes in it. And in those three genes, in that region - so some of them are in the bit of DNA that specifically reads for the genes and some of it is in the regulatory bits of DNA - and in total, we were looking at 60 variants, but my project specifically was looking at two variants that lie in the TBX15 gene itself.
Louisa: And so what we were able to do, because my PhD was linked with the Mary Lyon Centre is they generated two mouse models that had those specific human DNA variations in them, and we were then able to look at the mice and their whole body phenotype and whether or not they had any differences in their fat mass. So did they have more or less fat overall? Did they have their fat mass distributed across different parts of the body? So that was the basis of my PhD.
Sally: So are there genes that affect how much of a "beer belly" you've got, where your fat is located in your body?
Louisa: Yes, I think at the moment there's no one single gene that regulates it.
Louisa: I think what's quite obvious from the GWAS studies is that there's lots of different DNA variations that improve your susceptibility for getting a "beer belly" when combined with your diet, your exercise, your kind of general environmental factors that you're exposed to. I think there's a genetic predisposition to a certain body type, but that's then obviously exacerbated by our current modern human lifestyles.
Sally: Like everything in genetics, the answer is: it's complicated.
Louisa: Yes, yes, definitely.
Sally: So how do you then go from studying this within your PhD, within an academic setting, what made you think, "Hmm, I want to make that leap into a slightly different way of approaching science, and I want to go into an industry setting instead"?
Louisa: One of my big deciding factors when I came out of my PhD was I knew I wanted to have that tangible outcome to the work that I was doing. I loved academic research, I loved doing science, but for me it got quite hard towards the end doing research without there really being a kind of solid, definitive 'this is why we're doing it, and this will be the true impact of doing the work'.
Louisa: Whereas now, and particularly in the field that I'm in in industry, in that we're looking at drug safety testing, but it obviously then links back to genetics, I kind of feel like I've got the best of both worlds. So I'm still very much focused on genes and genetics, which is what I spent a lot of my academic career doing, but with that added benefit of, okay, well, I can see the reason why we're doing this work.
Sally: What piece of advice would you give to someone thinking about going into your field?
Louisa: My biggest piece of advice for someone that wants to come into the field would be to go out and contact local companies that are in your field of interest, or not necessarily in your field of interest if you haven't got that option, but any kind of industrial company and just get in contact and see if they're willing to kind of host you for a couple of days or a week during your summer holidays. And just try and get a feel for what it's like day to day in this kind of company, how the science works, because it might be very different to what you've experienced before, particularly through school. And it gives you an opportunity to talk to people and find out their different routes, because that's one of the things I've learned working here and kind of during my PhD is that people have very different routes through their scientific careers, more so than I ever realised when I was at school.
Louisa: I think it's really important to see that there isn't just one set way of doing something in science. I think there's a lot more variety and a lot more options open to you than people might realise. So we've got a degree apprentice, so she's come straight from her A levels. She's working four days a week in the company, in the lab. And then she spends one day a week going to university and doing a degree and learning the basic science to everything that underpins what we do here. But then we've equally got people that have gone through undergraduate degrees, master's degrees, PhDs, and a whole host of in between. So there really is no one route and don't be afraid to explore all the options available to you.
