For almost two years Dr. Anna Caballe has used molecular biology and biochemistry to study a cellular component, called the centrosome. Centrosomes are small organelles within cells that help coordinate correct separation of our chromosomes during cell division: the live imaging below displays a dividing early Drosophila (fruit fly) embryo, showing two fluorescently labelled cellular structures: microtubules in red, and centrioles, the core bit of centrosomes, in green. In particular, she is interested in understanding how cells undergo cellular division faithfully and appropriately as they should. Disruption of any of these steps can cause diseases such as cancer or developmental anomalies, such as microcephaly and dwarfism. Anna uses the tiny fruit fly as a model system; and combines genetics with high resolution microscopy to label and study proteins of the centrosome.
What most motivates you to do what you do?
A thirst for knowledge and understanding the basis for how our body works. I was always fascinated by that and how well coordinated everything is in our cells. They are like big cities, continually undergoing construction and things moving up and down in an orderly manner and often within specific locations.
What are the goals you most want to accomplish in your work?
I would like to carry out fundamental research and discover elements of our cells that could help understand or treat human diseases. My dream would be to have my own research lab and combine this with teaching at University level. More recently, I have become interested in science communication and outreach events. It is critical for scientists to communicate what we do to everyone and for the public to understand why we do what we do and that we are ordinary people trying to help advance knowledge further.
Who are the key mentors or people who deeply influenced who you are, what you believe in and what you're committed to in your work and life?
My parents and my older sister. We all have different jobs that require similar skills: well organized, thorough (quite stubborn too) and passionate about what we do! Getting into the sciences was a matter of following my curiosity. As a kid, I'd walk, climb trees, touch animals or anything I'd find, or get distracted when going on family hikes or trips. Then, I had an amazing high-school teacher who would tell us stories about being a scientist and taught us some basic lab work during Human Biology lessons. I knew then that I wanted to study that. I had good professors at Pompeu Fabra University, who motivated me into pursuing a career in biomedical research. During my PhD at Kings College London, my supervisor, Professor Martin-Serrano, taught me how to be a good scientist hard work, determination and rigour. Since I joined Professor Jordan Raff's lab, I am learning more on how to drive projects: step back now and then to re-think strategies and assess results, read more to get a better picture of the field, and supervising students is also teaching me a few things.
You recently published a breakthrough article. Can you tell me about that?
Yes, I am first co-author of Structural Basis for Mitotic Centrosome Assembly in Flies which can be found in the journal Cell. We wanted to understand the organising principles that allow centrosomes to assemble so quickly when cells enter mitosis (cellular division). Centrosomes are tiny and complex, and they contain hundreds of components. It had always remained a bit of a mystery and it was thought that mitotic centrosomes were an amorphous structure, yet they only duplicate once per cell cycle. Our work shows, for the first time, that mitotic centrosomes require a high specificity interaction and suggests there is an ordered structure at the heart of it. This work provides evidence of some of the key organsing principles required to make a structured scaffold underlying a functional centrosome.
Can you tell us about one of the more memorable moments during your research?
I had stayed until quite late in the lab the night before and the morning after I told my collaborator and co-author of the paper that I was surprised how one of the mutants behaved differently than expected. She said that she had noticed the same in her tests. I always labelled my mutants as M1, M2, M3, to make it as objective as possible. There was that short moment when I went to my lab-book to check my notes and verify which specific mutant I was referring (out of 12). It turns out that it corresponded exactly to the same mutant that my colleague had spotted having a similar behaviour using a different experimental technique, felt a bit like a eureka moment. It confirmed both our experimental assays were robust.
How would you describe the work you do, especially in this project?
A combination of dissecting and cooking. Conceptually, it is like a dissection because I like to “open up” or look through cells and observe and understand where each component or piece is and what it does. Practically, it is like cooking: mix reagents/ingredients, using different machines at different temperatures and to achieve processes and then observe (not taste!) the result. There's a lot of trial and error, like when you are trying a new dish and need to adjust components or amounts. We often follow protocols with specified concentrations and timings, very much like following a recipe. They often say that a scientist should be good in the kitchen!
What are the lessons for a colleague who might be embarking on a project similar to this one?
Enjoy a good collaboration with scientists with different expertise than yours, you can learn from them and you'll learn to trust and get excited by each other's science.
What did you learn from the people you worked with in this project?
To remain positive and believe in your data. I'd like to think our attitude helped us to get published in a high impact journal.