MBoC Early Career Researcher Spotlight: Hannah Opalko, PhD

Hannah Opalko, Biochem Cell Biology
Hannah Opalko, Biochem Cell Biology

The new research report “Design principles of Cdr2 node patterns in fission yeast cells” was recently selected as an MBoC Highlight. Our interview with the first author Hannah Opalko discusses cell cycle regulation, the beauty of fission yeast, and making the transition from academia to industry.  

Introduce yourself:

I became interested in science through my uncle who was a veterinarian and I thought that would be an awesome career. Then I realized I’m terrified of most small rodents so I quickly decided to look for other career options. I decided to pursue rodent-free science and did my undergraduate work at Mercyhurst University, where I got my first research experience with Dr. Steven Mauro studying how microorganisms affect E. coli in Lake Erie. I found I really loved doing benchwork, and I became interested in studying the mechanisms of how cells work. I did my graduate and post-doctorate work with Dr. Jamie Moseley at Dartmouth College, where I studied the relationship between cell size and the cell cycle using the fission yeast Schizosaccharomyces pombe as a model organism. I loved working with fission yeast, in part because of their simplicity. They are easy to use in lab and they have a simple rod shape that makes defects in cell size easy to identify and quantify. And it helps that I think the pathways that the Moseley lab works on are incredibly beautiful to image by fluorescence microscopy. Outside of science I enjoy gardening and baking, and as one often does when they live in New Hampshire, I have gotten pretty into rock climbing and hiking.

Favorite piece of scientific equipment/instrumentation?

This choice might be a bit controversial given it’s probably most people’s LEAST favorite, but my choice has to be the tetrad dissection scope. It’s essentially a microscope with a needle poking upward that you use to pick up and isolate yeast spores after mating them. One of the best things about working with yeast is how easy it is to cross strains to make cells with increasingly complicated genotypes. With the tetrad scope you use the needle to spatially separate each of the four spores that result from a tetrad, which is the result of two cells fusing during mating. The spores then grow to make four separate colonies, and you can test their genotype of each by plating on selective media, making it a really nice way to visualize Mendelian genetics. I find the process very relaxing, and it’s definitely something I enjoy while listening to a true crime podcast.

How did you become interested in your project?

Most of my work focuses on a cascade of protein kinases we refer to as the Cdr2 pathway, which in fission yeast regulates the cell cycle. This pathway functions to inhibit the mitotic inhibitor Wee1 and thus trigger division in response to factors like cell size and nutrient availability. What really interested me about this pathway is that it is organized into multi-protein structures that we call nodes, which localize to the plasma membrane in the cell middle. Localization of Cdr2 pathway components to nodes is necessary for normal Wee1 inhibition, and therefore a normal cell cycle.  In this most recent study, I noticed that in an arf6∆ mutant nodes accumulate on one side of the cell, which led me to wonder what other factors normally position them in the center of the cell. I was particularly excited about these questions because it’s increasingly well appreciated that many different signaling pathways are arranged in cluster-like structures, and I think by studying nodes we can learn more broadly about how this organization impacts signal transduction.

Can you explain the main results of your paper in a few sentences?

We found that the nucleus acts as a positive cue for Cdr2 node positioning to the cell middle and if you move the nucleus, Cdr2 nodes will accumulate next the nucleus at its new position. We collaborated with the Vavylonis Lab at Lehigh University who created particle-based simulations for node positioning. We were able to use this model to manipulate different factors that are known to regulate Cdr2, such as a cell tip-localized Cdr2 inhibitor (Pom1), a cortical tethering factor (Arf6), and the nucleus to see how these factors should affect Cdr2 localization. We could then test our model experimentally by deleting these regulators or changing the placement or number of nuclei in a cell.

Were any of your results surprising?

The most surprising finding for me was that there appears to be some redundancy built into controlling node positioning. For example, the presence of the inhibitor at the cell tips (Pom1) along with the cortical tether (Arf6) are sufficient for proper medial node positioning, even without the nucleus as a spatial cue. However, if you get rid of the tether by deleting Arf6, this diminishes node localization to the cell center. We found you can even make multinucleate cells that form really complicated patterns of inhibitor, nodes, and the nucleus, that made for an unexpected and interesting way to explore our model.

Why did you choose to publish your work in MBoC?

I’ve sent a lot of my work to MBoC because I think the journal publishes high quality papers. A lot of my research has been based off of papers published in MBoC. I also like that the journal reflects the diversity of the cell biology field both in topic and model organism so I think readers can always find something novel and relevant to whatever they are researching.

What are your next steps?

I’m very excited to have just started a job as a Scientist at Celdara Medical. They partner with inventors normally from academic institutions that have created therapeutics for human diseases with the aim to take their early-stage innovation into the clinic. The diseases that we work on and the techniques we use are very diverse so I’m always getting to learn something new.  I also find it very fulfilling to know that the projects I am working on will directly impact human health and patient quality of life.

About the Author:

Laura McCormick is a Graduate Student at Gupton Lab, Cell Biology and Physiology Department, UNC-Chapel Hill