Ask Away! Blog Series featuring Dr. Rosenthal

Welcome to our Ask Away! blog series where we delve into the fascinating journeys of faculty, staff and researchers at UC San Diego's Altman Clinical and Translational Research Institute (ACTRI).

Today, we are thrilled to introduce Dr. Sara Brin Rosenthal, the Associate Director for Research at the Center for Computational Biology and Bioinformatics (CCBB). With a robust background in biophysics and an impressive trajectory in computational biology, Dr. Rosenthal has significantly contributed to diverse research areas including genomics, liver disease, and network biology.

In our interview, Dr. Rosenthal shares her inspiring journey from studying biophysics to her current role at the CCBB. Join us as we delve into the experiences and challenges of Dr. Brin Rosenthal, whose work continues to push the boundaries of computational biology and bioinformatics, driving forward the quest for understanding and improving human health.

Could you walk us through your journey from studying Biophysics to becoming the Associate Director for Research at the Center for Computational Biology and Bioinformatics (CCBB) at UCSD ACTRI?
A: I discovered a fascination for genomics during grad school. While studying physics, we are taught to break down complex phenomena to their basic elements. It was astounding to me that the kaleidoscopic array of life around me was made from lists of ACGTs. I was floored by the simple elegance of the mapping of unique combinations of 3 nucleotide bases to amino acids, the building blocks of life. I wanted to devote my career to unraveling the dazzling complexity of genomics; how small changes in the genome lead to observable traits, particularly in the arena of human health.

After finishing grad school, I moved to San Diego from New Jersey, and started working as a Data Scientist/ Computational Biologist at the CCBB. It is hard to believe that was 9 years ago! In that time I have worked on projects in liver disease, neurodevelopmental disorders, arthritis, and hearing disorders, to name a few. In these projects we identified new disease genes and underlying pathways, and new avenues for therapeutic treatment. I love collaborating with a wide array of researchers, and it is so exciting to help push a project from hypothesis through to publication. I took on the role of Associate Director in the fall of 2021. We have a fantastic team at CCBB, and it is a true pleasure to work with such a brilliant team of scientists and engineers.

Your research covers a diverse range of topics from animal behavior to biomedical informatics. What inspired you to transition from studying collective animal behavior to focusing on bioinformatics and computational biology?
A: While I find collective behavior an endlessly fascinating field, after grad school I felt strongly that I wanted to spend my career in pursuit of improving human health. The computational and coding skills I picked up enabled me to transition fields relatively easily (and part of the fun and challenge to a career in computational biology is that the methods evolve so rapidly that everyone is always learning something new!). I was also able to transition my expertise in network analysis and graph theory to applications in computational biology. In particular, we strive to understand how genes and proteins interact within a cell, and how those interactions may be changed in different disease states.

As the Associate Director for Research, you manage complex research projects in collaboration with principal investigators across UCSD. Could you share some insights into how you balance the diverse demands of such projects while ensuring their successful execution?
A: You are right- it can be demanding at times! Especially around grant submission season, we tend to be slammed by new requests. I have found it is best to be as realistic as possible with folks about timeline. Then it can be a pleasant surprise if it turns out we get to it faster. Good communication is the key to successful execution. Much of our role at CCBB is in interpreting the bioinformatics in a way that researchers from biological backgrounds can understand, and conversely, identifying the correct tool or method to address the biological research question.

Your work in multi-omics analysis of liver disease has contributed significantly to understanding molecular features and potential therapeutic targets. What sparked your interest in this area, and what do you envision as the next steps in liver disease research?
A: I have been fortunate to collaborate on a number of projects in liver disease. Chronic liver disease impacts many millions of folks around the world, and is an area in which UCSD researchers are particularly strong. As is the case in many fields, science is built on relationships. After our first project was finished, we wanted the collaboration to continue, and thus follow up studies ensued!

Could you discuss your experience as a guest lecturer at UCSD, teaching courses in Marine Biotechnology and Network Biology? How do you integrate your research expertise into your teaching approach?
A: Network analysis has been a common thread to my research- networks are a particularly flexible framework. If you have a system that can be broken down into individual elements, and connections between those elements, you have a network. This can be applied to schools of fish, social networks, or interacting genes and proteins in a cell. Much of my teaching has revolved around this framework.

As a mentor to undergraduate interns, what strategies do you employ to guide them in their research and analysis projects, helping them develop as independent researchers?
A: It is so rewarding to introduce young students to research. It is a different experience from the classes and problem sets they are used to. We don’t always know the answer in research! I try to give students room to explore, make mistakes, and figure things out on their own (checking in periodically to make sure they don’t go too far astray). I also try to emphasize the importance of communicating results in a way the audience will understand, and to start a presentation by motivating WHY we are doing what are doing- I have found students often assume their audience knows as much as they do, which is never the case when the student has been deep in a research project all summer.

Could you share any memorable moments or challenges you faced during your research career that significantly influenced your trajectory or perspective in the field?
A: It is hard when we discover an experiment hasn’t worked. This can be due to a number of issues, including technical problems upstream of the analysis, or a lack of true biological signal in the data. Either way, the researcher has spent a lot of time and money running the experiment, and getting data sequenced, so it is always disappointing to have to break the bad news. No one said science was easy!

Lastly, what advice would you give to aspiring researchers, particularly those interested in interdisciplinary fields like computational biology and bioinformatics, based on your own experiences and insights gained throughout your career?
A: I have a few pieces of advice for aspiring computational biology researchers. 1) Always read the paper! It can be easy to get a cool new piece of software installed and running, but if you don’t understand the underlying processes you can get into trouble. 2) Be skeptical of your results. Triple check everything. I have learned the hard way that if a result looks too good to be true, then you probably had a typo somewhere. 3) Talk to the experimentalists and/or biologists. They have invaluable knowledge about the system/disease at hand, and can often spot problems in the results that a pure computational scientist might miss.

We thank Dr. Rosenthal for her time and insightful contributions to this interview, shedding light on her remarkable journey and groundbreaking work. Don't forget to email us at researchcomm@health.ucsd.edu or v3chavez@health.ucsd.edu if you have any additional questions for her.

Feel free to send any questions you have about research our way!

UC San Diego ACTRI Communications