ABSTRACT
First Person is a series of interviews with the first authors of a selection of papers published in Journal of Cell Science, helping researchers promote themselves alongside their papers. Abhishikt David Solomon is first author on ‘ γ-tubulin mediates DNA double-strand break repair’, published in JCS. David is a PhD student in the lab of Dr Aimin Peng at the Adams School of Dentistry, University of North Carolina at Chapel Hill, NC, USA, investigating the molecular mechanisms of DNA double-strand break repair and genomic instability in the context of cancer biology, with the aim of identifying potential therapeutic targets for drug discovery.
Abhishikt David Solomon (left)
How would you explain the main findings of your paper in lay terms?
Your whole body is governed by proteins that keep your DNA intact and functioning in a proper way. This is done through advanced cell-to-cell communication, in which other cytoplasmic proteins such as microtubules help regulate cell machinery throughout cell division and the cell cycle to protect our nuclei and chromosomal DNA from damage. Sometimes, due to external factors or internal problems, this communication is disrupted and the whole system malfunctions. In humans, this can be caused by long-term chemical or radiation exposure, or internal factors like improper cell division or genetic and chromosomal defects. This leads to enhanced cell division, proliferation and the onset of cancer, leading to tumor growth. In such cases, cell surveillance systems and DNA repair mechanisms are also affected. Nevertheless, some key proteins that have been shown to regulate this complex set of pathways hold therapeutic potential. We identified a new candidate protein, γ-tubulin, as one of the key mediators of the DNA double-strand break (DSB) repair pathway. γ-tubulin is a centrosomal protein responsible for nucleating microtubules from their highly dynamic minus ends, which is important to ensure proper mitotic spindle nucleation during cell division. We have found that targeting this additional, new role of γ-tubulin in microtubule-independent activities represents an effective strategy to eliminate carcinogenesis, because γ-tubulin deficiency leads to aberrant tumor growth and dysregulation of DSB repair. Recruitment of γ-tubulin into the nucleus to DNA damage sites indicates a direct involvement in DNA repair. Moreover, its association with DNA repair factors is increased in the presence of DNA damage, suggesting that it has an important role in DNA repair activities. γ-tubulin inhibition in cancer cells, combined with established chemotherapeutic drugs, abrogates tumor growth.
Were there any specific challenges associated with this project? If so, how did you overcome them?
Some of the techniques used in our paper require immense hard work, especially when you are new to them, but we put in the troubleshooting and effort needed to address the issues. That's what makes a PhD scholar a true researcher.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
During my immunoprecipitation (IP) experiments and the laser recruitment studies, I realized that γ-tubulin is directly involved in the DNA damage response. The recruitment of γ-tubulin to laser-induced DNA damage sites was very clear and exciting to visualize under a confocal microscope, which provided highly advanced timelapses. We observed this for the very first time, which made us think about possible repair mechanisms γ-tubulin might be involved in. The IP also took a lot of effort to complete, and the immunoblots I eventually got were so neat!
Why did you choose Journal of Cell Science for your paper?
Journal of Cell Science has been a pioneering journal from both a traditional and modern perspective. It provides critical scrutiny of the research articles it publishes, and that is the reason I chose this journal.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
I thank my advisor, Dr Aimin Peng, who made this work possible and motivated me throughout my doctoral degree. I really admire his mentorship, willingness to help and humility towards his students. I also thank my committee members, who helped me in shaping my research aptitude. Also, I thank my graduate peers who have helped me in making my research successful.
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?
It was the willingness to serve people that helped me pursue my field of research. In my internships during my undergraduate degree, I was very surprised by and wanted to learn more about the variety of DNA repair mechanisms and their regulation in the context of cancer. This led me here, to extrapolate more of these pathways.
Who are your role models in science? Why?
My role models are my parents, family and all my advisors who helped me pursue my dream of studying and doing research at world class research universities and helped motivate me for such goals.
What's next for you?
I will continue to do research and would love to stay in academia as an independent investigator.
Tell us something interesting about yourself that wouldn't be on your CV
I am a musician! I am trained in Indian classical vocal music. I also play guitar, bagpipes, recorder, flute and basic piano. During my undergraduate years, I did modeling too! On the outdoor front, I also trained as a cricketer during my early years of high school and have captained my cricket club for several years. I have played cricket for my university in the Midwest Conference National Collegiate Cricket Association tournament. I have also won several awards for all of these activities.
Abhishikt David Solomon's contact details: Adams School of Dentistry, University of North Carolina at Chapel Hill, 385 S Columbia St, Chapel Hill, NC 27599, USA.
E-mail: [email protected]
