Temporarily Danish David

The last two months I’ve been working in Aarhus, Denmark, and I thought it might make an interesting post to explain why and what that looked like.

Mostly not quite as pretty as this (from the top of the ARoS art museum in Aarhus)

The Royal Society of Edinburgh offered Saltire Early Career Fellowships, for people early on in their independent research career like me to visit researchers in the EU to collaborate. These collaborations could lead to new pieces of research, grant proposals, new skills, and other outputs that I wouldn’t be able to produce just staying in Aberdeen, Scotland, or the UK. I was eager to collaborate with Prof. Trine Bilde at Aarhus University to work on social spiders as they are fascinating little critters (living in highly inbred groups in southern Africa, they cooperate in prey capture and raising their young) and Trine’s work on their genetics and evolution is world-leading. In July 2021 we wrote an application to look at how these animals, which due to their mating system have very low genetic diversity, cope with being infected, as normally genetic diversity can somewhat protect populations from disease. Luckily, it was successful, and so fast forward several months and I have been in Aarhus, learning as much as I can about social spider genomes and bioinformatics.

What was that last word? “Bioinformatics” – it’s a combination of biology (most often molecular biology like genetics), statistics, and computer science. Bioinformatics is how we go about analysing the genes and proteins that underpin the phenotypes that we can observe of animals, plants, and other organisms. If we’re looking at every base pair (each pair of C and G or A and T nucleotides) in a genome, or every amino acid in a protein, we’re talking about really huge data sets (the human genome is about 3 billion base pairs, while the social spider Stegodyphus dumicola’s is around 4 billion!) and so some clever statistics and gnarly computer science is required to handle this and not leave bioinformaticians in a muddled, confused, sweaty heap.

Makes for cosy bedtime reading, no?

While I’ve done plenty of statistics throughout my research (someone might say too much) and I’ve handled datasets large by the standards of animal behaviour (using a data set of 30 years of squirrel observations or data based on 1000s of hours of cricket videos will do that) this is a whole different ball game. Typical datasets have millions of rows and you might be dealing with several of these simultaneously, and asking questions that require various simulations or analytical inference that require vast computing power. Part of the justification in my application to the RSE was that learning a new bioinformatics skillset would allow me to do a whole range of new things, from conducting new analyses and writing new papers, to supervising a wider range of student projects and writing grants on more subjects. I’ve been seeing bioinformatics appear more and more in the journals I read and in the conversations about grant proposals with colleagues and I didn’t want to miss out on all the fun. So, only a little apprehensive, I loaded the hound into the car, drove from Aberdeen to Hull, got the ferry to Rotterdam (despite the best efforts of Storm Eunice), and then drove to Aarhus for around two months of sudden immersion in bioinformatics, mostly under the guidance of Dr Jesper Bechsgaard.

While I was really looking forward to working on the research project, I was also very much looking forward to travelling to a new place, meeting new people, and seeing how they do things there. Of course, the pandemic has reduced our ability to do this for the last 2+ years. I was excited to go to Aarhus, and Denmark in general, as it’s a part of the world I haven’t been before, and Aarhus has a growing reputation. But honestly, I could have been going anywhere and I would’ve been pretty jazzed about it. Plus, weeks before I arrived the Danes has dropped pretty much all COVID restrictions, and I was quite looking forward to a return to “normal” life.

Well, as normal as it gets just after a war in Europe breaks out

And how has it gone? Well, of course at the start there was a learning curve, where I seemed to spend days trying to fix a relatively simple coding problem, or my brain, so used to whole-organism evolutionary biology, struggled to get to grips with how we study the workings under the hood, down among the genes. Some of those problems I worked through, and others I simply gave up on and found a work around (I did finally crack parallel for-loops that named new files after their directory and subdirectory!!!) But after that, things gathered pace, and I’ve managed to explore how DNA methylation, the addition of a methyl group to a cytosine base, changes once a social spider colony starts to die off. We know from previous work that colonies have increased bacterial loads in the months before they wink out of existence, and we also know that in other organisms DNA methylation helps change the regulation of genes that play a role in the immune system. By comparing the DNA methylation profiles of “healthy” colonies with those about to die off, we can therefore see if DNA methylation helps control the immune response in these social spiders. Better understanding this would be really cool as it might give insights into how other species that are inbred and live at high densities combat pathogens. I won’t spill the beans on what we’ve found here, but that will be coming in a pre-print in the next few months and then a peer reviewed article some time after that.

Now I’ve got some bioinformatics chops, I’m also eyeing up other questions. What role do the existing microbes have to play when a social spider gets infected? Do social and non-social species differ in their patterns of methylation, and in the enzymes they have that add, remove, and interpret methyl groups? Why do cockroaches, one of the other species I now work on, have higher levels of methylation than many other insects? Do the positive or negative effects of social interactions have a basis in changes in methylation patterns, or other epigenetic factors? Now I’m working on and thinking more about these different processes I have a much better appreciation of the gamut of really interesting questions out there. Additionally, having some of the skills necessary to explore these questions means I can talk and write much more convincingly about them, hopefully opening up a whole new world of interesting collaborations and research projects on the molecular underpinnings of evolution and behaviour. I’ve also just found it utterly fascinating that I can scroll through the nucleotide code of an immune gene, and then find out where that particular gene is found in the genome of my study species, and if particular cytosine bases in that gene have gained or lost a little methyl group. Its truly amazing that we have got to the stage where we can just read the code of life on our computer screens like that; at times I’ve been spell-bound.

Or at least going cross-eyed

Beyond work, I’ve explored the local countryside (its largely flat and muddy, not unlike where I grew up), been to the odd museum and done other touristy things, eaten much, much more than my own body weight in pastries, and enjoyed checking out “Aarhus Street Food” most weekends for a delicious selection of street food from round the world, all under the roof of an old bus station (Aberdeen, can we please get something like this?). Popescu has conversed with the resident Danish dogs, and has found the local “hundeskov” to his liking. We’ve been sharing a room during our stay, and one of the highlights of this has been his nose and wagging tail acting as a second alarm clock, seconds after my first one goes off. Travelling with him made things much more difficult (driving and the ferry across two days rather than a flight or two, sorting out his travel documents as well as mine [thank you Brexit…], finding medium-term accommodation that was happy with a dog, etc) but its also been a very rewarding experience and I am looking forward to taking him more places now we’ve done this trip.

Now I’m back in the UK, but I will be still working mostly on the RSE project until late June. Then I’ll be writing up our results and trying to get them published and working on the next grants to continue this line of work! I was sad to leave Aarhus (and all the Danish pastries…) but I am very much looking forward to finding out where this line of inquiry leads in the future. The genomes of animals hold many mysteries, and now I at least have some idea of how to start studying them.

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