Marco Trizzino is an assistant professor at Thomas Jefferson University, in Philadelphia. Dr. Trizzino studies evolutionary genomics, with a focus on transposable elements. “Transposons are not just parasites. It’s becoming more and more clear that they are also used by the genome in a mutualistic relationship to perform important functions for the genome itself, such as gene regulation,” he says. His lab is particularly interested in young transposons – transposable element families that have recently colonized the human genome. One of these, the SVA transposons, are the topic of his recent refereed preprint at Review Commons, which has since been published at PLOS Genetics.
Dr. Trizzino got his master’s degree and Ph.D. at Sapienza University in Rome. In 2014, he moved to the University of Pennsylvania for a postdoc. In between, Dr. Trizzino took a couple of years off, working for Istituto Oikos, an environmental NGO in northern Italy.
Was it easy returning to academia?
Well, it took a little bit of adjustment – also because it was a new country, with a completely different approach to life and to research and to work. But it was okay. I went to Philadelphia, to the University of Pennsylvania and I’ve now been in Philadelphia for eight years.
You established your lab in the second half of 2019 – you were starting a lab just before the pandemic broke. How was the experience of becoming a new PI a few months before the world shut down?
I would say that in that terrible situation I got lucky because the entire world shut down in early March and in February I had gotten notice of the award of two grants. One was a big foundation grant and one was a five-year NIH grant. That gave me a little bit of peace of mind and allowed me to say “okay, I’ll take these next few months to hire people”. I advertised positions. I did a lot of interviews. As it turned out, when things opened up, in the summer of 2020, I had 3 postdocs, and a fourth postdoc who was going to join a few months later in January – plus a graduate student who was rotating and ended up joining my lab. She’s actually the first author of the Review Commons paper, Sam (Samantha Barnada).
Could you walk us through the main conclusions of your PLOS Genetics paper, the one that was submitted through Review Commons?
We looked at SVA (SINE-VNTR-Alus) transposons, of which there are three thousand copies, give or take, in the human genome, of which nearly half are human-exclusive, meaning that they are not even found in the chimpanzee. By profiling histone modifications in iPSCs (induced pluripotent stem cells), we see which ones are in an active state – meaning that they are not repressed by repressive methylation, DNA methylation or histone methylation. They are labeled by histone acetylation, which means that they work as active regulatory elements. Then we try to understand why. We look at what’s different in these SVAs that are active compared to the ones that are repressed in iPSCs and we saw that there was enrichment for very specific motifs for OCT4 and YY1 transcription factors next to each other.
We demonstrated that there is sequential binding in these two motifs by these two transcription factors in the SVA elements that are active. When we repress these roughly 700 SVAs by putting repressive methylation on them with CRISPR interference and we look at the consequences on gene expression, we saw that there were big changes in the expression of hundreds of genes and that the binding of OCT4 and YY1 were not happening anymore. So we really demonstrate that these SVAs are active because they provide binding for important transcription factors.
These SVAs are active because they provide binding for important transcription factors.Marco Trizzino
Several of our authors have commented that they find the Review Commons referee reports to be more collegial or more constructive than normal journal reviews. What was your experience like?
They were very constructive. At the end, both reviewers signed the comments, so we actually know who the people are, and they helped a lot. Everything was very smooth, very quick. We went to PLOS Biology first and they said: “you know, we think it is a better fit for PLOS Genetics“. So we went to PLOS Genetics, and they looked at the comments and accepted. It took three months from the first submission to Review Commons to the paper being accepted, which is by far the fastest that has ever happened to me.
PLOS Genetics did not recruit any new reviewers for the manuscript?
No, they just sent it quickly to the same reviewers and asked if they agreed with the comments (the authors’ response), and within two weeks the reviewers said “yes” and the paper got accepted.
Were there major changes between the refereed preprint and the journal paper?
No, not at all.
If we can have this paper, or this refereed preprint, that has been reviewed and which is, in terms of content, very close to the final published paper, what do you think is the main function, or what are the main functions, of journals in 2022?
First of all, I would say that I am a big fan of preprints in general. I really think we could live, potentially, a life without journals at this point, if we all would think the same way. But of course, journals are still important – if I publish a preprint, it’s going to reach a certain crowd, a certain audience. But if the paper goes into a specialized journal, it’s going to be more likely that people in the specific field are going to read the paper. I think that is right now the main role of journals. But I would envision a future where journals don’t have to take care of the peer review process anymore, that they just host a paper that was reviewed by a third party, someone like Review Commons.
I think that the journal should be the home for a paper, where there is an audience that always reads genetics journals or immunology journals or developmental biology journals, and that’s going to help to get attention for the paper. But I think the whole process of peer review is handled much better by entities like Review Commons. I think Review Commons is the future and it should work like that for all journals. It’s more professional, it works just better.
I would envision a future where journals don’t have to take care of the peer review process anymore.Marco Trizzino
Let’s go back a bit to your life in science. You’d done a master’s and a PhD in Italy, gone to work for an NGO, and a couple of years later, you decided to return to academia. How did you choose your postdoc lab?
I really wanted to work with next-generation sequencing data because eight years ago it was clearly booming in the United States as a field but in Europe, we weren’t quite there yet. I was looking for a postdoc where I could gain that kind of experience. I saw that this PI at U Penn, Christopher Brown, was looking for postdocs and was doing exactly that kind of work. After the interview, he said, “if you join I’ll give you the freedom of choosing your project”. So we designed a project that was tailored for me, with an evolutionary biology background, on the evolution of gene regulation in primates that then led to a couple of papers.
After that, you did a second postdoc.
I was not ready to go on the job market looking for a faculty position. I’d done a lot of bioinformatics in my first postdoc and I wanted to get a little bit stronger on the wet bench side before trying to become an assistant professor. It was still in the field of gene regulation, although it had a much stronger biomedical focus. That allowed me to learn a lot. We did a lot of proteomics, which I’d never done before, a lot of mass spectrometry, and all sorts of techniques that I was not accustomed to.
In terms of bioinformatics, were you mostly self-taught?
No. The first year especially, my advisor sat with me and explained a lot of things. Then I attended a lot of boot camps and workshops organized at U Penn on Python and R, and thankfully there was another postdoc in the lab who was 100% a bioinformatician, who taught me a lot. There was a lot of self-teaching as well, but I would say I had a lot of mentorship, especially during the first year, year-and-a-half which was really important for me.
Is there anything you recommend for Ph.D. students or postdocs who want to learn bioinformatics?
R is really important. Whichever field you work in, it doesn’t matter if you are a neuroscientist or a cancer biologist. There are a lot of resources to learn R, Coursera courses, workshops, and all the universities now have an R class. I would really recommend to everyone to learn R.
When do you think is the best time to post a preprint?
We normally do it when the paper is ready for submission to a journal or to Review Commons. We do it on the same day, preprint and submission. Because at that point the paper is ready to see the world. Some people I know wait for reviewer comments to come back and then if they are addressable, they put the paper out. But I think it’s not worth it. Even for grant applications now preprints are highly regarded. Having a preprint out is only going to help you. It shows productivity.
Having a preprint out is only going to help you. It shows productivity.Marco Trizzino
Do you normally get feedback when you post a preprint?
Not on the bioRxiv platform, much more on Twitter. If I tweet my preprint, there is a lot of feedback, but if I just leave it on bioRxiv, I’ve never had a comment.
You’ve used preprints both as a postdoc and as a PI. During your postdoc, was it hard to convince your mentor to preprint?
In my first postdoc, Christopher Brown was a big fan of preprints. He’s the one who introduced me to preprints. In my second postdoc, we never preprinted because my PI was afraid of scooping. Now he’s preprinting, he’s now also a fan. But in the first few years, he was afraid that if we put a preprint out we’d get scooped, which in my opinion is exactly the opposite. If you put a preprint out it shows that you were working on it before. So there I had to push a little bit for it. Now in my lab, it’s basically a requirement that every paper is supposed to go as a preprint.
And your PhD students and postdocs are all okay with this?
Yeah, they’re okay with it. No one has ever complained.
So preprints are the new normal?
I think it’s the new normal, absolutely. It has to be.