Moving beyond Darwinian notions of evolution with the humble fruit fly

Tara-Lyn Camilleri-Carter is a PhD Candidate from Monash University in Australia. She recently published a literature review in Journals of Gerontology titled “transgenerational obesity and healthy ageing in drosophila”. This article summarizes the existing evidence surrounding the idea that obese parents can pass on a predisposition for poor health outcomes to their offspring. In order to improve population health, it is crucial to understand these risks and how they can present across multiple generations. The fruit fly (Drosophila melanogaster) is used to model and study these evolutionary challenges. Tara-Lyn is passionate about evolutionary ecology and conservation, and we chatted via Zoom about her recent article and how her lab is expanding on our classical understanding of evolution by studying the fly.

This is the first of a series of chats with women in science featuring their publications as leading authors. If you know someone who has recently published a scientific manuscript who would like to chat with me, you can get in touch via Twitter @laurenpoppi or email lauren.poppi@rutgers.edu.

 First, congratulations on your recent first author review paper! What was the motivation for you and your group to compile this review?

A couple of reasons. The first reason was that, as you said, we could see that there was a gap in the literature. We decided to write it at the beginning of my PhD, for other reasons. I suffer from chronic illness, so I spent especially the start of my PhD quite ill, getting treatment for and recovering from a vector-borne disease that I picked up during field work. I was quite sick, but I wanted to still make progress. So we said… “this review article – we want to write it – why don’t we just write it now? Why don’t I just jump in and start writing it now?”. When I was at home a lot, I still wanted to do something in the brief moments that I was feeling well enough. So that’s how it came about really. Personal circumstances and also identifying that this isn’t really well known and is still so emerging (this field of transgenerational effects).

Why are flies (drosophila) such a good model for the kind of research that you do?

 I love flies. I really honestly love flies. They are so good for a lot of reasons, but first of all, I’m coming at these problems from an evolution perspective. We call them a ‘model species’ and they are such a great species to use when trying to put frameworks around things that might be evolutionarily conserved. We do share, for example, 60% of our disease-related genes with drosophila. We have a lot of conserved metabolic pathways or analogues to our pathways and our genes. So they make a really good model for that work, and one of the things that I really like about them is that we can generalize.

We don’t want to overstate our results, but we can actually say it probably applies to a lot of living organisms, and that’s essentially why I moved into working in the lab I work in now. I wanted to look at more fundamental, evolutionarily conserved processes. They’re also really good because of how genetically tractable or easy to work with [they are]. You can breed thousands of them in a really short time. There is so much known about them. There are so many different variants that you can use. You can do an experimental evolution study with flies in six months. You can get through ten generations in a very short time. For someone like me who recognizes the need to use other species in research, but it’s just not something that I can personally do myself. So, I am morally and ethically comfortable with using something like a fly.

How was the experience of going through the review process -  the literature review, writing, editing, and then getting to see it in print?

It took a really long time to pull it all together. It wouldn’t be a far stretch to say it was a year, maybe a little longer, to see it finally published. My co-authors are my current PhD supervisors, so they are really great to work with. Even though it takes a long time, we still turn drafts around pretty quickly and work together really well.

I was also lucky in that the review process was one of those dream review processes where everything was constructive and reasonable, and you felt “yeah! that will make it better” or “yeah, they are right about that.” It felt like everything we were getting was enriching instead of it being like other cases where it is really disheartening. So even though it was really long and it was a lot of work, I feel that [the process] was enjoyable overall. I still often think, when I’m writing things now, “wait… I wrote something about that in the review. I’m going to go back through and read it… what papers did I cite there?” So, it’s really helpful to me to have it all out there as well.

 And – you can cite yourself in your thesis!

Exactly!  (Laughs)

In your review you talk about how obesity in parents might negatively impact the healthy ageing of offspring, even across two generations. What are the current thoughts on how this risk is passed between generations, and how might the conferred risk of developing chronic diseases like type II diabetes later in life be managed?

I guess the answer to this is slightly convoluted, in that how the risk is passed is quite simple, in that it is thought to be epigenetic effects and changes in pathways that affect nutrients and things like that. I guess my real interest is in why the risk is passed on, I want to get at that evolutionary aspect of it. We hypothesize that it’s a result of phenotypic plasticity, which describes this situation where the parental environment, or the grandparental environment will affect the offspring beyond just the transfer of genes alone. And so, there is a question there then. Are these effects from the mother or the father?

There are a lot of questions… but let’s just say that there are effects, which I have found that there are effects from the mother, and the father, and the grandmother, and the grandfather… so which is most important and how do they interact? Are they adaptive? Who is selection favouring here? Who gets the best outcome here? In other words, the diet that is optimal for the parents - is it the same diet that is optimal for the offspring? Or is it not? So that leads to whether it is adaptive, and what the nature of this plastic response in phenotypes actually is. It’s this transfer of something that’s being transmitted from generation to generation, and that feeds nicely into it is being caused by these mechanisms, by these histone modifications or epigenetic effects, to change the way nutrients are used and absorbed, or how pathways work essentially.

In terms of how the risk of developing chronic diseases [might be managed]… I really don’t know. I’m very conscious in my work, because again, I’m looking at it from this evolutionary ecology perspective. I love that it is relevant to the medical discipline, and I love things like evolutionary medicine and seeing how those two things can interact, but I’m conscious of this is what I’m doing, and I’ll let the biomedical community interpret it however they will, and take it to answer questions like that. I’m conscious not to overstep my expertise there.

That was a fantastic answer. Do we know if is adaptive or maladaptive for these traits to be transferred?

In the evolutionary literature currently, it’s a split debate. The traditional thinking is that it doesn’t matter whether it’s diet, or immunity, or whatever the environment is, if the environment matches that of your parents, that should be a good thing. Your mother particularly (most studies are done on maternal effects) will prime you for your environment. So then if you are in a situation where your environment mismatches, that 'should be’ bad for you. But there is also a whole lot of new evidence that suggests that may not actually be the case. Selection might actually be favouring the fitness of the mother, over and above the fitness of the offspring. It makes sense, I guess for me, what I am finding, is maybe the latter. Maybe it doesn’t so much matter if there is a match between environments - that maybe optimal conditions for one might not necessarily be optimal conditions for the other. Just because we might be favouring more offspring from the mother or healthier offspring from the mother, to an extent, but that might not translate into absolutely every health or fitness indicator in the offspring being better.

That’s cool. It really challenges our classical understanding of evolution.

It’s more an extension of our classical notion of evolution. It gets into the nitty-gritty of what would happen in this situation for parental effects. Because no one has really looked at how those effects interact either. What does happen if the mother and father have different diets? And something like that you can apply to an obesity perspective.

Does it mean that if somebody was in a nutrient-sparse environment, and the mother primed them to go into this almost malnourished situation, and then they are born into a situation where [nutrients are] in abundance… does that make them more predisposed to obesity, or not? And so, the answer to that is maybe yes, but with all of these effects and intergenerational effects, I always make sure that I say that it’s only small changes in risks. What your parents ate is never going to be as important as what you eat, of course. I don’t want to freak anyone out that their fate is sealed or anything like that. We are still just investigating all of these things, and these are small effects that we are looking for.

Going backward in time a bit now, when did you first know that you had a passion or an aptitude for science, and along the way who have been some of your biggest role models or mentors?

I knew that I had an interest in science, long before I thought I might have an aptitude for it. I have had a pretty indirect path to academia. I did a psychology degree straight out of school, but I was living out of home at the time… and I thought, “I don’t want to go on to be a psychologist at 20 years old”, three more years felt like so long, and so long struggling financially. So, I went full-time where I was working, which was IBM at the time, so I ended up spending about eight years in the IT service industry. I was essentially a manager, I guess. By the end I was working for the Victorian Government, and I was a service center manager. But through that time, I started volunteering for the Orangutan Project, raising money for different conservation efforts, and I was really into all numbers of pop science books. I started to think “oh, I love this stuff so much. It feels so much more interesting than what I am doing, maybe I should quit and go back to uni”.

I eventually made the decision to do that. I got into a Bachelor of Science at Monash, and then ended up leaving that for a Masters program at ANU (Australian National University). At each point, I thought “I love it, so I will just try it until I fail.” I still have this mentality where “I’ll just try that and if I’m not good enough, they’ll tell me." But then I realized that I do have some sort of aptitude for this - I’m not failing as much as I thought I would be. So, I eventually thought, “Ok. Alright. I have an aptitude for it!” It took a lot of years for me to realize that. Even when I had a meeting at ANU, I said, “Look, I have done the psychology degree, and I am halfway through this Bachelor of Science, this is where I want to get to.” And this lady at ANU - she was amazing. She just said, “stop doing so much undergraduate [study]. If this is what you want to do, get into doing postgraduate [study]. Go for this Masters program.” And that blew my mind. I thought, “Oh, is that something I can do? That’s amazing.” When I very first started, I had no idea what a PhD was, or how to get into science at all.

In terms of role models, it’s really tricky. I feel like I have met a lot of people now that I wish I had met when I was younger. You are [a member of] Graduate Women in Science, yes?

Yes!

The committee that I am on is ‘Graduate Women in Victoria’, and this has a lot of amazing, unsung hero women that you just absolutely will never hear about unless you Google them, because they don’t blow their own trumpet or anything. There are just so many amazing women that have achieved so much, in science and in academia. I am sort of surrounded by them now, but I wish I had known them when I was really young.

I know that this is a loaded question when you are in the midst of a PhD, but what are some of your career goals and aspirations?

I am hoping to be able to continue in research. I’m hoping to keep going with academia, and we will see what the current climate brings with that. We don’t know right? I’m not that worried. I’m not so concerned. I feel like I will end up in academia one way or the other, but if there are no opportunities, I am also interested in other areas of scientific impact. Another area that I am really interested in is science policy, politics, and how you can actually make broad changes for the community. I really love evolution research, I’m super passionate about it, I definitely want to keep doing that. But I also, in tandem, as a roundabout path, I’m happy to go wherever I can make the most impact or wherever I feel is meaningful. Who knows? Hopefully I’ll continue in academia.

How do you hope to see the scientific landscape changing for women in the future?

Even just in the last 10-15 years that I have been working, I can see that a lot has changed for the better already. I am grateful for that. I think the change that we need to see in the scientific landscape reflects that change we need to see in leadership positions generally. I think that we’ve often got women really well-represented at entry level positions but not at the upper levels, and in these leadership positions, and this seems to be the same everywhere. It seems to not be specific to science, and it's worse in politics or disciplines like mathematics or computer science where you can see that there is a large discrepancy. My hope and dream would be that one day you hear about an amazing female leader, and you just hear about the leader, you don’t hear about the female part. This person did this amazing thing, and not have this conversation about woman/female. This is my dream. You can see in the current climate that there are a lot of prominent female scientists being left out of the COVID19 coverage. We have a lot of bias to correct. We need to correct what we think of when we think ‘scientist’ and ‘leader’.