A Conversation with Massa Shoura, PhD, 2017 Arnold O. Beckman Postdoctoral Fellow

What was your research focused on? Please note any significant results.

My project was focused on understanding the fundamentals of how multicellular organisms process information and respond to genetic and environmental change. It seems that one way cells do this is by rewiring their DNA to add diversity to the genetic code that enables adaptation to new environments and to cellular functions that are dictated by developmental needs. I sought to resurrect an observation that was made in 1970s showing that although human DNA (or chromosomes) consist exclusively of linear polymer molecules with non-changing sequences, there also exist extrachromosomal DNA elements that are circular. These elements were hypothesized to expand the coding repertoire of our genome and correlate with disease; such as cancer. Technological challenges associated with isolating this circular component of the genome were major obstacles to advancing this field. With the support of the Beckman foundation, I was able to develop new tools and novel genomic assays that usher in a new era for circular DNA and helped reestablish extrachromosomal circular DNA as a field of study.

Did your AOB Postdoc research lead to unexpected findings?

Yes! Although extrachromosomal circular DNAs were thought to be present in diseased states only, due to the unprecedented sensitivity of our assays and the unbiased approaches we implemented, we discovered that these circular DNAs are present in normal cells as well! Though, the repertoire of circular DNAs (or, to use the term we coined, the Circulome) is highly cell-type dependent. Thus, in some cases it is possible to use these DNAs as a “fingerprint” of disease. Further, we discovered new circular DNAs that originate from a gigantic muscle-protein gene called Titin. This observation was not reported before. It is significant because these circles seem to be conserved across species (worms and humans) and are produced in a cell-type-specific manner (skeletal muscles and cardiac cells). This could reflect one or both of the following: (i) a selectively advantageous DNA rewiring process that is happening in muscle cell development and/or (ii) a confluence of biochemical effects from the interaction of DNA transcription, replication, repair, and tolerance for sequence diversity that cause specific regions of the genome to acquire sequence & structural instability in specific cell types. All in all, my work provides evidence for cell-type-specific, genomic heterogeneity at a number of previously assumed-to-be static (or non-changing) genes.

How did the experience change your thinking about science and conducting research?

Academia is a stressful environment. The postdoctoral period comes with lots of deadlines, expectations, and external (and internal) pressures that constantly remind you of how fast your clock is ticking. The AOB postdocs provided a community of highly supportive peers, in addition to being super smart and fun! It is amazing how we all got along so well and continue to support each other. The AOB Program Manager & the Foundation Director (the amazing Catrina Bryant and Anne Hultgren, respectively) went above and beyond the call of duty. They provided a very nurturing environment for all of the postdocs and were very generous with their time, in addition to being very attuned to our needs. The annual Beckman Symposium was a great opportunity for postdocs and young PIs to interact, talk about the science we are doing, form collaborations, and discuss career paths. Additionally, I benefited from the various boot camps that were offered- from how to give a talk to how to write a grant and run a lab. The Foundation invested in our wellbeing as scientists and people (the swag, the gala, and the numerous fun activities were also pluses!)

What effect did the AOB Postdoctoral Fellowship have on your career?

The award has benefited my career in multiple ways. Firstly, it allowed me to pursue my own scientific questions independently. When I joined Andrew Fire's lab, it was expected that new postdocs would chart their own scientific endeavors independently (with Dr. Fire's counsel). This is highly adventurous for postdocs who would like to work on a project of their own that they can later “take with them” to start their lab in academia or industry. I could not have been able to pursue this unique scientific endeavor without the Beckman Fellowship. Secondly, the level of exposure Beckman postdocs get is not matched by other programs. As an AOB Fellow, I was able to attend and participate in the Beckman Grant Workshops, discuss some cutting edge research topics, and gain experience in both evaluating and advocating for new ideas. Lastly, being a Beckman postdoc is a “stamp of approval” that opens up other doors. I was able to build on the findings supported by the Beckman fellowship to advance my career by publishing 10 papers (more are in the works), and receive new fellowships/awards/grants, etc.

Do you have any advice for our current Beckman Awardees?

Keep calm and follow Dr. Beckman's Seven Rules for Success!

Any additional thoughts?

I cannot overstate how important this award was to me. Indeed, it has been THE major stepping stone of my career! It provided a young scientist, who was just charting her path, with an unparalleled level of support and a boost of confidence that was much needed. Without a doubt, the best experience I have had as a postdoc was to be a member of the Beckman family. I am so thankful (and lucky) to have had this experience. I will always be ready to give back to the Foundation if I can be of any service.