Strengths and challenges of working with non-model organisms

There was a time when there was no such thing as a “model organism.” In the 19th century, Marine Institutes flourished all over the world and hosted labs where scientists could take advantage of the rich diversity of sea flora and fauna to explore how cells work. The 20th century marked a sharp turning point and introduced the concept of model organisms. Scientists decided that in order to explore a specific aspect of biology, it would be more efficient to study a simple and tractable organism. Bacteria, yeast, worms, flies, and mice became the logical choice. These organisms became superstars when many tools and resources were developed specifically to work with them. During those years, all the “other” organisms were seemingly neglected. However, nowadays low sequencing prices and new gene targeting techniques have opened the lab doors to “old systems” and “alternative organisms.” A number of articles beautifully highlight the need for studying diverse organisms (see Gladfelter, 2015; Russell et al., 2017). Studying the biology of new organisms that are taken straight from their habitat is important because many model systems we use in the lab are no longer representative of their species (reviewed in (Alfred and Baldwin, 2015)). This year the growing interest in non-conventional model organisms is supported by the Emerging Model Systems special interest subgroup session at the 2017 ASCB|EMBO Meeting.

Meanwhile, many scientists have based their research on alternative organisms. Ania Czarkwiani did her PhD at University College London on skeletal regeneration in brittle stars. Her experience perfectly summarizes the choice of working with a non-model organism: “The pros of working on non-(yet)-model organisms are certainly the excitement of often discovering completely new things, and having a much nicer and more cooperative community. The cons are of course the technical limitations of having to establish methodologies for studying them, often with limited human resources.”

What are the pros and cons of working with an organism that is not a model organism? I reached out to scientists at different career stages and institutes to hear about their experience and share it with you. These are the take-home messages from them.

Studying more organisms can give us a more rigorous and authentic view of biology

Stefania Castagnetti is a group leader at the Villefranche-sur-mer Developmental Biology Laboratory. Her lab studies the mechanisms controlling chromosome segregation and how this process is adapted to the fast early embryonic divisions. “We decided to use sea urchins as a model, as large amounts of early embryos could be quickly and easily obtained,” Castagnetti says. “We soon realized that sea urchin embryos do not behave like frog and fish embryos. That prompted us to look at more species to determine whether there is greater variability in how embryos respond to mitotic problems than what was previously observed.” She also explains that she now works on emerging systems because: “eventually to fill the gaps we had to go to the sea and find new species for our work.

Early cleavage starfish embryo (tubulin in green, DNA in blue). Image credit: Zak Swartz

Zak Swartz is a postdoc at the Whitehead Institute. He is interested in how the cell division machinery adapts itself for various developmental contexts, particularly in meiosis “I enjoy working at this interface between cell biology and developmental biology, so I need an organism that enables an interdisciplinary approach,” Swartz says. “Starfish make millions of oocytes, which allows me to do proteomics. We can trigger meiosis in vitro with great temporal control and synchrony. Fertilization and development occur externally in a rather inexpensive medium: seawater. The oocytes and embryos are optically clear, allowing for great imaging. Finally, there is a growing list of molecular tools that enable robust functional testing, as well as genomic resources.”

A supportive environment is important to work with new organisms

Which is the best environment to face the challenges of working on a new species? “This project and the approach we are taking are only possible because we work in a Marine Station,” Castagnetti says. “For our studies, we need access to lots of early cleavage embryos and marine invertebrates provide many of those. As a yeast person I had very little experience with early embryos and would not have been able to take the project off the ground without the help I got from everybody, from teams to support staff”.

On the other hand, a heavily biomedical department like at the Whitehead Institute can be supportive with scientists working with alternative organisms. “People will always be genuinely excited about good science if the justification is strong,” Swartz says. “For me, working with starfish in such an environment has helped me learn how to better articulate the reasons for choosing a “non-canonical” organism.”

Adult Patiria miniata in the lab tank. Image credit: Zak Swartz

Working with a new organism is not easy, but it is exciting!

For her research, Castagnetti needs to work not only with one non-model system but many. “For the new species, we have to start from scratch, figuring out simple things like their reproductive season, how to obtain mature eggs, how to treat the embryos. Even to film untreated embryos we have to figure out how to mount them. So for each animal, we have to start all over again,” Castagnetti says. “But then every experiment tells us something new, even the ‘simple’ live imaging of control embryos, which had never been looked at before.” Indeed, in an era where new discoveries in model systems go very fast, developing new tools for alternative organisms can be seen as a limitation. Elaine Seaver is a Professor at Whitney Laboratory for Marine Bioscience who works with the annelid Capitella teleta. From her experience, she admits that: “People working with such organisms [non-model] benefit if they have a pioneer spirit with a willingness to develop new tools as they navigate through a project.”

Non-model organisms and the scientific society

  • How do scientists working with model system see their “alternative” colleagues? As you may have noticed reading articles or going to meetings, scientists working with alternative organisms are still a minority. “Some folks don’t take the work being done in these systems seriously and don’t see value in using such study organisms,” Seaver says. “Other folks are curious about the ‘creepy crawly’ animals like them and support the efforts of those who work with non-conventional animals, but would not seriously invest their own careers in such systems (too chancy from a career perspective). And others really appreciate the value of studying a wide range of organisms and understand what each system contributes to our greater understanding of a particular problem. This latter group tends to have a better foundation in comparative biology or evolutionary biology.”
  • Which are the differences between the communities of model and non-model systems? Scientists who work with alternative organisms feel that their community is close-knit and supportive, and there are fewer chances of being scooped. In contrast, working with a well-studied organism also means a more competitive community. Antonella Ruggiero is a postdoc at the Centre de Recherche en Biologie Moleculaire in Montpellier, where she studies cell cycle regulation in the budding yeast. “Working with yeasts you can do (almost) whatever you imagine,” she says. “You can easily find collaborators, but there are so many labs and it is a super competitive field, so you have to go faster and to have really good ideas!” This can be stressful and unhealthy for some of us, and as Seaver says: “I do best when I do not feel that I am racing to beat competitors all the time.”
  • How does working with non-traditional organisms affect funding sources? Sam Dundon is a postdoc at Yale. She worked with the multinucleated fungus Ashbya gossypii for her PhD and now has moved to the traditional fission yeast. In her experience: “Justifying studies using even established model organisms can be difficult, but rationalizing a non-traditional system can be even more challenging. I honestly do not think of this so much as a problem specific to non-traditional systems, but see it as a reflection of the overall challenges of “basic biology” research in the current funding climate.”

Final considerations

One of the aspects to consider is: “are model organisms representative of nature?” When we read “this mechanism is conserved from yeast to human,” what does it really mean? How do we know that the other hundreds of species in between share the same mechanisms? Model organisms have been incredibly useful to discover many cellular mechanisms in a relatively short period of time. Moreover, focusing on these organisms we were able to develop some of the most powerful scientific techniques that are currently at our disposal. The good news is that nowadays scientists can use most of these tools to study even more diverse organisms to unravel the diversity of life.

The views and opinions expressed in this blog are the views of the author(s) and do not represent the official policy or position of ASCB.

References:
Gladfelter, A. S. (2015). How nontraditional model systems can save us.
Russell, J. J. et al. (2017). Non-model model organisms. BMC Biol. 15, 55.
Alfred, J., and Baldwin, I. T. (2015). New opportunities at the wild frontier. Elife 4.

About the Author:


Margherita Perillo is a postdoctoral fellow at Brown University, where she studies germline stem cells in development using primarily the seastar as model system. Previously she was a postdoctoral fellow at Boston College where she studied nuclear positioning at the neuromuscular and myotendinous junctions. She earned her PhD from the Open University of London working at the Stazione Zoologica Anton Dohrn in Napoli, where she studied cell-type evolution. Email: margherita.peril@gmail.com; twitter: @Marghe_Perillo

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