Multiple pathways of toxicity induced by C9orf72 dipeptide repeat aggregates and G4C2 RNA in a cellular model

Publishing the research results is a major aspect of a researcher’s life. How these results are published can have a major impact on research and its community. What happens if we share outcomes openly, make data public, publish the comments received from colleagues, or test the academic outcomes of other researchers? This falls under the denominator of Open Science, as part and parcel of academic quality. At UMCG, we promote the principles of Open Science by putting every month the spotlight on an academic article that scores well on certain aspects of Open Science, like reproducibility, open peer review, open source, open access.

This month we focus on the journal eLife with the Open Science Publication of the Month May: ‘’Multiple pathways of toxicity induced by C9orf72 dipeptide repeat aggregates and G4C2 RNA in a cellular model” by Frédéric Frottin, Manuela Pérez-Berlanga, F Ulrich Hartl, Mark S Hipp, published in eLife volume 10, Article number: 62718 (2021).

The group of dr. Mark Hipp at the department of Biomedical Cells and Systems (UMCG) focusses on understanding protein aggregation in neurodegenerative diseases, such as Alzheimer’s disease and Amyotrophic Lateral Sclerosis (ALS). In their recent publication they investigated in a cellular model why an ALS causing mutation in the C9orf72 gene is toxic and which mechanisms contribute to this toxicity. They found out that the toxicity of the mutation is evoked by multiple pathways at once. By unravelling the mechanism of toxicity through protein aggregation and toxic RNA step by step dr. Hipp and his group hope to understand how these pathways of toxicity contribute to neurodegenerative diseases and how to counteract this toxicity. Hopefully, leading to new treatments for neurodegenerative diseases in the future.

eLife: Pioneering in open science

eLife is a journal that seeks to encourage and recognize responsible behavior in research, and to promote a research culture that supports collaboration, diversity and inclusion, and openness. They support preprints and open-science practices, and publish articles on different aspects of research culture. Dr. Mark Hipp recognizes the pioneering approach that eLife has: “eLife started with having a different approach towards publication. For example, they believe the impact factor is not the important part, they want to publish good science even if the impact factor goes down.” Hipp admires this approach, but also states that it can be difficult to convince young researchers, because they can be very focused on getting a high impact factor. With their open peer review trial (read lessons learned) in 2018 eLife tested a novel approach. “They published your paper including the comments and left it up to you if you want to address them or not. They really try to do new things, be more open, get out of the normal way.” Their approach results in much more work for everyone involved, but it is always good to try new things out, believes Hipp. eLife also got a lot of funding, which shows the support from funders for this open approach.

Open ánd responsible science

Hipp and his group choose to publish in eLife on purpose:  “I like the idea behind the journal and we wanted at least one paper in eLife, because we wanted to show that we support the approach.” He believes that it’s is part of a scientist’s responsibility to share their knowledge. “We need to understand that if we receive money from the state or a foundation, we have an obligation to use the money correctly, this means that we have an obligation that other people can use this information, tools and data as well.” He also refers to researchers that retire: “It would be a shame it every time that somebody changes field or retires, all this knowledge gets lost.” 

On the other hand, Hipp believes in responsible science where scientists get credit for their research. “What I like very much is bioRxiv, a pre-print service. You cannot submit to eLife without making preprints and I think that is a very good approach. We have a good experience with that. I am a big fan of putting the data out there, but I think it is important that you can have some control about what happens with it. I don’t like the idea if something is not published yet, that everyone can use your data without even telling you. Sharing the data in a responsible way is something that I love to do, but I think it needs to be clear it is someone’s work and this person needs to be mentioned if you use those data. We make a lot of tools,  and we are happy to share those tools if people ask us.” 

A comprising factor: high open access fees

Hipp also raises an important issue about open access publishing: the high fees. “If you have to pay 10.000 euro for open access, you have to ask yourself how much open access it really is.” eLife tries to do this differently. For the first five years of existence they asked no publication fee, and currently they ask a certain amount to cover their publication costs (read more). This is a good development, because currently some people can simply not afford the high open access fees of some journals. Hipp believes that ‘no scientist is against open access’, but that the fees make it very difficult. “I think it is a bit of a ‘Wild West’ at the moment. There are a lot of funding agencies that mention open access publishing as a requirement, but the fees are very high, how can they solve this issue?”

Inspiring others

With her open science philosophy eLife is also inspiring other journals. Hipp mentions the journal EMBO: “They have a transparent process and publish the reviewers’ comments. This is also a great tool I like to give to students. I tell them: read this paper, read what these three people [the reviewers] commented and do something with it. And the same with datasets, I tell my students to look at it and to play around with it.”