The Season’s Script: Tales of Metabolic adaptation #MetabolismMondays

All the world’s a metabolic dance, early career scientists are leading the way!

Emerging perspectives in metabolism

This week we’ll meet Dr Karin Van der Burg, a new faculty at Clemson University. Karin’s introduction to seasonal adaptation came during her undergrad first-year biology lecture, when she first heard about butterflies changing wing colors depending on temperature. “I thought that was SO COOL!” she recalls that moment. Her first encounter with phenotypic plasticity shifted how she saw development. Since then, Karin’s curiosity has led her deep into the physiological and genetic mechanisms that allow insects to tune their development to the seasons. From hormones and gene expression to chromatin and cold tolerance, her work spans multiple levels of biological organization. She’s studied butterflies that color-shift with the calendar, and budworms that shut down development to survive freezing winters. Now at her own lab, she’s combining genetics and physiology to explore how environmental cues like day length, temperature and seasons get integrated by hormonal systems to shape development using the Buckeye butterfly, Junonia coenia, and other incredible insect models. At heart, her science is driven by one thing: a need to know how it all works. Check out her lab page here. Give her a follow over Twitter and Bluesky. Keep an eye for announcements because she will soon be hiring postdocs and students in her lab !

What was your first introduction to the study of seasonal adaptation in insects? Tell us about that moment and how it shaped your scientific path? 

I believe the first time I heard about this was in first year of college, in a lecture from Dr. Paul Brakefield. He told us about Bicyclus anynana, a small brown African butterfly species that changes its phenotype depending on rearing conditions. Exposure to cooler temperatures leads to a dull brown phenotype, which is adaptive in the dry season, while exposure to warmer temperatures results in the development of colorful wing eyespots, which are more adaptive in the wet season. At the time I thought that was SO COOL!

This was basically my first introduction to phenotypic plasticity: the phenomenon where multiple phenotypes could be created from one genotype. It really changed my perspective on how organisms develop and grow; I used to believe it was a very deterministic process, but instead it turned out to be very adaptable.

Tell us what sparked your interest in the connection between endocrine signaling and seasonal adaptation? Walk us through your journey into studying the genetic and physiological basis of seasonal adaptation and introduce us to the field.

What really drew me in was the idea that phenotypes are plastic. At the time, work done in the evolution group at Leiden University did a lot of research in hormonal signaling underlying this plasticity, and I was fortunate enough to be able to do my undergraduate research project in that group. My project focused on genes associated with DNA methylation. It didn’t really go anywhere, but it was my first introduction to hormonal signaling and epigenetic signaling possibly working in concert.

As I continued my education, into my master’s and my PhD, I really started to think about how endocrine signaling affects epigenetic changes, which in turn results in changes in developmental pathways, resulting in different phenotypes. I realized to truly understand how organisms respond to seasonal changes, we need to look at the complete picture, and not one small aspect.

During my PhD I did mostly genetics research (with Dr. Reed at Cornell University), looking at genetic changes involved with changes in butterfly wing color plasticity. I also looked at changes to gene expression and chromatin accessibility, with a little bit of endocrine signaling, all to understand how seasonal plasticity in butterfly wing colors can evolve.  While it was really interesting, I did feel like I was too focused on one aspect of a phenotype (in my case, butterfly wing color), and not the organism as a whole. I felt like there were many more changes involved in seasonal plasticity. Thus, for my postdoc I switched to a much more physiology focused lab (Dr. Marshall at UBC) to really get that more holistic perspective. To really understand how insects adapt to seasonal conditions, I believe we need to look at insect holistically, and not just one small aspect.

You have worked with different model systems including budworm Choristoneura fumiferana, and the common buckeye butterfly Junonia coenia. Tell us about your experience of working with these unique systems. What advantages do they offer in studying seasonal adaptations?

The biggest advantage is that these two organisms allow me to investigate two different types of seasonal adaptation; J. coenia has two flight seasons a year, an early and a late summer season. Each season has different conditions, such as temperature, rainfall, and food availability. We can use that to investigate how insects survive and reproduce in different conditions. Most notable about this butterfly is its change in wing coloration: butterflies emerge with a pale tan color when reared under warm, long-day conditions, and a dark red color when reared under cold, short-day conditions. Very likely there are other seasonal adaptations too, although they are not well known.

C. fumiferana, or the eastern spruce budworm, is really interesting in that it only has one lifecycle per year, and it is also stationary in the northern boreal forest. That means it needs to survive winter, with truly harsh conditions. Some very extreme changes in phenotype are necessary to survive under those conditions. My main interest is in the diapause phenotype, a prolonged period of arrested development during the early larval stages that allows for survival during harsh winters.

I like the combination of the two, because it allows me to study survival and reproduction in multiple different seasons, with very different survival strategies!

Tell us about your work on butterfly wing color plasticity. What were some of your key findings regarding the genetic factors controlling changes in wing color plasticity? Specifically, how does the upregulation of metabolites like trehalase contribute to the environmentally induced and genetically assimilated red phenotype?

During my PhD, I did a big research project on seasonal wing color plasticity in Junonia coenia. As I mentioned, in the wild this butterfly displays seasonal wing color plasticity, but we found we can easily manipulate this through artificial selection, such that plasticity was lost in only a few generations. We found three genes to be involved in this loss of plasticity, trehalase, herfst, and cortex. Later, my colleagues found that it probably wasn’t cortex regulating plasticity, but ivory, a long non-coding RNA. (Fandino et al., 2024; Livraghi et al., 2024; Tian et al., 2024).

Trehalase was indeed a very interesting find! The gene is upregulated under cold conditions in Junonia, and in other insects it is involved in cold-hardening. Trehalose (the sugar) can act as a cryoprotectant (prevents hemolymph freezing), and it is involved in metabolism.

We hypothesized that trehalase may be involved with the production of red pigments as well, because the ommochrome pigment that produces the red color contains a sugar molecule.

It’s really interesting to hypothesize on the multiple roles trehalase might play in seasonal plasticity. For example, it could be that the involvement in red pigmentation is a secondary effect; where trehalase was upregulated at first to manage cold conditions, and later was co-opted to produce red pigmentation as well! I will say that this is mostly speculation at this point, but it is definitely a research avenue worth pursuing.

Butterflies rely on endocrine cues to regulate metabolism and developmental timing. How does the ecdysone signaling pathway integrate environmental information to drive seasonal phenotypes?

These are really, really good questions! There is a lot of evidence that ecdysone signaling in butterflies is a universal regulator of seasonal plasticity (Bhardwaj et al., 2020). Given that ecdysone signaling is responsive to changes in day length, it is likely that circadian genes are involved, although that mechanism is not well worked out in insects.

Can small changes in endocrine signaling lead to tissue-specific adaptations without widespread disruptions. How does this level of regulation evolve, and what makes it so flexible?

Again, very good question. There are two things at play here: the seasonal responsiveness of ecdysone signaling, and the ability of seasonal plasticity to rapidly evolve. I believe overall development is very robust against predictable seasonal changes in ecdysone signaling. Tissue specific adaptations, such as wing color and wing shape in Junonia, or eyespot size in other nymphalid butterflies, can evolve rapidly to become more or less responsive to fluctuations in ecdysone. I suspect that outside of predictable seasonal changes, fluctuations in ecdysone signaling would be very problematic for normal development. I think (I may be wrong) the reason why plasticity can evolve so rapidly is because the seasonal responsiveness system (ecdysone signaling) is so robust and thus predictable, and so it makes for a reliable internal cue to adjust tissue specific developmental programs.

How does natural selection shape the regulation of hormonal pathways involved in adaptation? Are there evolutionary constraints that limit how endocrine signaling can be modified?

I think we know very little about the evolution of hormonal pathways itself! There are almost certainly many constraints on how endocrine signaling itself can evolve, because hormonal signaling is involved in so many different things. I believe that natural selection can readily act on downstream receivers of endocrine signals, but maybe not so much on the ecdysone signal itself. I’m happy to be proven wrong here though!

Speaking of your experimental approach – What have been the biggest challenges in studying endocrine regulation of seasonal adaptation? Are there specific experiments that were particularly difficult to execute? Did you have to deal with midnight timepoints or require an army of undergrads/ long hours etc.

Ecdysone measurements are a huge pain… Much harder than any of the genetic analysis I’ve done; ATAC-seq /RNA-seq / CRISPR/Cas9 were all a breeze compared to ecdysone measurements. It appears such a straightforward experiment, but I was constantly dealing with broken HPLC machines, degradation of ecdysone samples in the freezer… And yes, many late night or early morning sampling time points. I did all the sampling myself, but I did have an army of undergraduate students to help rear all the caterpillars!

Looking ahead, what are the next big questions in understanding how endocrine signaling and metabolism intersect with seasonal adaptation?

I’m very interested in exploring the interplay between circadian rhythms and ecdysone signaling! How/why is ecdysone signaling so responsive to external cues?

What role does curiosity play in your life, both within and outside of science? Why do you choose to work on insects?

Ultimately, I just want to know how stuff works… I enjoy thinking about biological research questions that integrate external and internal factors. I landed on gene regulatory mechanisms because for me, that’s where the bridge is between hard-coded DNA and the final phenotype which is very dependent on external conditions. I mostly work on insects because they are easier to work with than mammals, and because many insect species are very important to us.

Have you noticed a shift in how researchers approach insect biology?

Definitely have seen a shift to consider organisms more holistically, integrating factors at multiple levels of biological organization. I also feel like the scientific community is a lot more aware how important external conditions such as seasons are! So yes, I definitely think so.

Tell us about how you see the future of adaptative metabolism evolve with the new upcoming tools – what techniques have you used and which tools are you most excited about?

Single-cell RNA/ATAC-seq, and new CRISPR/Cas9 applications…

I haven’t worked with single cells yet, but I’d like to in the future! I’ve worked a lot with gene-editing through CRISPR/Cas9, but new techniques using CRISPR are coming out regularly and it is very exciting.

Were there any pivotal moments that shaped your career path? What’s an unexpected place you’ve found inspiration for your work? What advice would you offer to students and early-career scientists?

I was in a very genetics driven lab during my PhD, working with Bob Reed at Cornell. During my PostDoc, I shifted to a much more physiology-oriented lab, working with Katie Marshall at UBC. That shift really cemented that I wanted to integrate physiology and genetics research. I’m not sure this is ‘unexpected’ but I get most inspired from conversations with other folks, especially new students. The questions I get asked, especially ones that I don’t know the answer to, are really inspiring!

For advice, always be willing to consider new perspectives, and never be afraid to share your own thoughts, even if you’re not super confident. Science is a group effort!

How do you maintain a balance between your rigorous research activities and personal life? Are there hobbies or practices you find particularly rejuvenating?

These days I have a child, and that forces me to put down work when I’m at home! Otherwise, I love crafting! For example, making quilts or knitting.

If you hadn’t embarked on a career in biological research, what other profession might you have pursued, and why?

I truly don’t know – Before I found biology I tried engineering for a year and failed miserably. I feel like biology is the alternative career path for me and it has worked out well so far!

Anything you’d want to highlight for the future?

I’ll be looking for a post doc this coming year! I’ll make a more formal announcement soon. I’m also rounding up a big project that I started in my postdoc on local adaptation in spruce budworm, I’m very excited for that!

Last week we learnt about how cancer cells rewire their metabolism to alter their cell fate and proliferate, check out – Switching Gears – Metabolic rewiring in cancer (Luis Cedeno-Rosario).

Check out the article All the world’s a metabolic dance, and how early career scientists are leading the way !!

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