First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping early-career researchers promote themselves alongside their papers. Magdalena Cardenas-Rodriguez is first author on ‘ Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases’, published in JCS. Magdalena is a research assistant in the lab of Jose Luis Badano at Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Montevideo, Uruguay, investigating the cellular processes that are altered in cilia-related human diseases.

Magdalena Cardenas-Rodriguez

How would you explain the main findings of your paper in lay terms?

Ciliopathies are a group of human genetic disorders caused by mutations in genes related to cilia function. Motile cilia are responsible for fluid propulsion, while primary cilia serve a sensory or signaling function. Mutations in CEP290, a large multidomain protein, have been associated with at least five different cilia-associated syndromes. Even though more than 130 mutations are known in CEP290, it has been challenging to establish clear correlations between mutations and cellular defects. In this work, we studied why the way cep290 expression is inhibited influences the resulting phenotypes. Using different models of gene inhibition in zebrafish we showed that acute knockdown caused severe cilia phenotypes, while defects in a mutant genetic line were milder and restricted to the retina. We showed that milder phenotypes were associated with a genetic compensation mechanism by genes involved in a common subcellular process, and that this may be a conserved mechanism contributing to genotype-phenotype variations observed in CEP290 deficiencies.

Were there any specific challenges associated with this project? If so, how did you overcome them?

Yes! Working with Cep290 was a big challenge because it's a big protein with several functional domains. Gene expression inhibition and proving specificity of the phenotypes was quite tricky. Also working with zebrafish always has some extra challenges since some specific reagents, such as antibodies, are not always available. But we were able to overcome them by producing our own reagents to achieve our goals.

When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?

When we were able to rescue the cep290-deficiency-related phenotypes by overexpressing the compensatory candidates genes, it was a great moment because we realized that we were on the right path. Also, confirming our results on human samples was a great moment too.

Why did you choose Journal of Cell Science for your paper?

I always follow articles from Journal of Cell Science. I like the broad spectrum of topics in cell biology that it covers. Papers are clear, focused and well presented. Also JCS has published hallmark papers in my field from groups that I consider to do rigorous and interesting science. I highlight the supportive programs for meetings, travel fellowships and promotion of young researchers that The Company of Biologists offers. I am happy that our paper was accepted in this journal.

Cep290 localization in zebrafish retina. Wholemount immunofluorescence in 56hpf wild-type embryos showing Cep290 localization at the photoreceptor connecting cilia. Green, anti-acetylated tubulin; blue, nuclei stained with Hoechst; red, anti-cep290_CTerm. Scale bar: 20 µm.

Cep290 localization in zebrafish retina. Wholemount immunofluorescence in 56hpf wild-type embryos showing Cep290 localization at the photoreceptor connecting cilia. Green, anti-acetylated tubulin; blue, nuclei stained with Hoechst; red, anti-cep290_CTerm. Scale bar: 20 µm.

Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?

Throughout my career, I have been able to work with extraordinarily talented and amazing people from whom I learned a lot. In Uruguay, I was lucky to have a supportive PhD mentor, Dr Jose Badano, who encouraged me to expand my horizons and look for postdoctoral opportunities abroad. Working with Dr Iain Drummond during my postdoc in Boston was an incredible experience. I was able to learn a lot, not only technical aspects but also on how to manage a lab, build collaborations, think thoroughly and how to enhance people's skills. But most importantly, he was supportive and patient when I became a mom and helped me go through that wonderful but challenging period.

What motivated you to pursue a career in science, and what have been the most interesting moments on the path that led you to where you are now?

Since I was a child I have always liked nature, animals, and I loved to watch Jacques Cousteau and David Attenborough documentaries. So although I wanted to become so many things, when I grew up I knew that science was a tempting option. During my career as a MSc and PhD student I had the opportunity to assist at several international courses abroad where I met wonderful scientists who encouraged me to continue doing science and overcome difficulties.

Who are your role models in science? Why?

I don't have one specific role model. I like those scientists that proposed general biological questions that are still not completely resolved and try to think out of the box. I like the work of those groups that clearly show teamwork. I take as role models those scientists who care about the career development of their students and who are generous when it comes to sharing merits, projects and results.

“I take as role models those scientists who care about the career development of their students and who are generous when it comes to sharing merits, projects and results.”

What's next for you?

In 2020, after finishing my postdoc in the USA, I returned to my home country, Uruguay. I′m working as a research assistant in the Institut Pasteur Montevideo where I′m building my own line of research focused on renal diseases, an important national health problem. I seek to consolidate an interdisciplinary work group to enhance the capacities and resources that we have. Also, one of my goals is to become a committed mentor, helping new scientists to explore all their skills and enjoy doing science.

Tell us something interesting about yourself that wouldn't be on your CV

I love hiking and all kind of outdoor activities. I have fun exploring nature, travelling and experiencing new cultures.

Magdalena Cardenas-Rodriguez's contact details: Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020 Montevideo, Uruguay. E-mail: mcardenas@pasteur.edu.uy

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Genetic compensation for cilia defects in cep290 mutants by upregulation of cilia-associated small GTPases
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J. Cell Sci.
134
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