ABSTRACT

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. Mélody Wintrebert is joint first author on ‘Activation of meiotic recombination by nuclear import of the DNA break hotspot-determining complex in fission yeast’, published in JCS. Mélody conducted the research described in this article while a Master’s student in Gerry Smith's lab at the Fred Hutchinson Cancer Research Center, Seattle, WA. She is now a PhD student in the labs of Frédéric Relaix and Laurent Tiret at Institut Mondor de Recherche Biomédicale, Créteil, and Ecole Nationale Vétérinaire d'Alfort, Maisons Alfort, France, investigating cellular and molecular biology.

Mélody Wintrebert

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

For accurate meiosis, necessary for reproduction, each pair of chromosomes needs to segregate correctly. This works thanks to the prior pairing and attachment via recombination that forms crossovers between chromosome pairs. The synaptonemal complex, or LinEs (linear elements) in Schizosaccharomyes pombe, is critical to pair these homologous chromosomes and to make DNA double-strand breaks for recombination. A major LinE component, Rec10, forms a complex with other LinE proteins (Rec25, Rec27 and Mug20) in the nucleus in meiotic prophase and stimulates DNA breakage. In this publication, we identified a multipartite Rec10 nuclear localization signal (NLS). Moreover, we show that this NLS in Rec10 is necessary to bring other proteins of the same complex into the nucleus, suggesting the formation of the LinE complex prior to nuclear entry.

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

When I first came into the lab, I was supposed to construct a strain carrying Rec10–GFP on a plasmid and introduce different mutations I had designed into it. I got stuck at the very start of the project, failing over and over, trying different strategies and never getting the right sequence. With great help from Sue Admunsen (a staff scientist) and Gerry Smith, we managed to start the project from another angle, introducing mutations in Rec10 in a Rec25–GFP strain, allowing a more stringent screen of the mutations and an easier way to start.

Another big challenge was the distance. I spent only a few months in Gerry's lab for an internship before going back to France to finish my studies. I had found some really interesting results, but the work was far from finished. Mai-Chi Nguyen, first co-author of this paper, took over the project, confirmed my results and went further to support our hypothesis. So I would like to say a big thank you to Mai-Chi, and good luck for med school!

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

Following the turnaround at the start of the project, molecular biology became way easier, and really quickly I was in front of the microscope to check cellular localization of Rec25, knowing that it was possible that a totally different process could be the cause of the recombination decrease I had already observed. But seeing these speckles in the cytoplasm for the mutation I designed was a great relief and really exciting!

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

Journal of Cell Science is a great journal with a wide audience interested in cellular biology, so it can give our results the best audience to appreciate this work.

“When you see the problem with a fresh eye, you usually get a ton of new ideas.”

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

Gerry was, and still is, an amazing mentor, even though I am not in his lab anymore. He and Sue Admundsen were the first to show me how to perform experiments in a microbiology lab. But more than that, Gerry gave me tons of advice, from which journal to submit this manuscript to, to career choices, and even life advice. Some of it really stuck in my head, like ‘One hour in the library can save you one week in the laboratory’! But one of the best pieces of advice and the best memory I have from my time in Seattle is that when a project is not working, you have to take a step back, take a big breath of fresh air and refocus your mind. When you see the problem with a fresh eye, you usually get a ton of new ideas.

Mutations in Rec10's NLS block the nuclear entry of Rec10's partner Rec25–GFP, leading to the formation of aggregates in the cytoplasm.

Mutations in Rec10's NLS block the nuclear entry of Rec10's partner Rec25–GFP, leading to the formation of aggregates in the cytoplasm.

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?

Initially I didn't want to do research, and my childhood dream was to become a vet. But things didn't turn out as planned, so I had to find another goal. Both my parents are in the research field (not in academia), and I was initiated very early to scientific reasoning, curiosity and researching my own answer when my parents were tired of answering the infinite ‘and why?’ I didn't stop asking.

What's next for you?

I'm just starting my PhD, and even if studying yeast and meiosis was my first subject of interest, I have decided to change my perspective, not doing research on yeast, but using yeast. In my new project, I am using Saccharomyces cerevisiae as a tool to perform an efficient drug screen. I'm using the common points between mammals and yeast to decipher genetic and molecular pathways involved in a mitochondrial myopathy.

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

I'm a black belt judoka and like crocheting (yes, people can do both!).

Mélody Wintrebert's contact details: IMRB, Inserm U955, 94010 Créteil and Ecole Nationale Vétérinaire d'Alfort, 94704 Maisons Alfort, France.

E-mail: wintrebert.melody@orange.fr

Reference

Wintrebert
,
M.
,
Nguyen
,
M.-C.
and
Smith
,
G. R.
(
2021
).
Activation of meiotic recombination by nuclear import of the DNA break hotspot-determining complex in fission yeast
.
J. Cell Sci.
134
,
jcs253518
.