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. Md Noor Akhtar is first author on ‘ Hominini-specific regulation of the cell cycle by stop codon readthrough of FEM1B’, published in JCS. Md Noor is a PhD student in the lab of Prof. Sandeep M. Eswarappa at Department of Biochemistry, Indian Institute of Science, Bangalore, India, where his research focuses on unravelling the mechanisms of genetic recoding and its physiological significance.
Md Noor Akhtar
How would you explain the main findings of your paper in lay terms?
Cell cycle dysregulation is a hallmark of diseases such as cancer. FEM1B protein regulates the cell cycle by degrading the stem-loop binding protein (SLBP), which is required to maintain normal levels of replication-dependent histone proteins, which are essential for cell cycle progression. Our study shows that ribosomes translating FEM1B mRNA continue translation beyond the stop codon instead of terminating, generating a C-terminally extended protein. The resulting isoform is highly unstable and undergoes ubiquitin-dependent proteasomal degradation. Thus, stop codon readthrough (SCR) of FEM1B mRNA regulates FEM1B protein levels and, therefore, the cell cycle. Interestingly, this is a recently evolved phenomenon observed only in humans and chimpanzees (tribe Hominini). Thus, our study has identified a recently evolved oncogenic translational event that might partly explain why humans are more susceptible to cancer among primates.
Were there any specific challenges associated with this project? If so, how did you overcome them?
To understand the physiological significance of SCR of FEM1B, we aimed to delete a proximal part of the 3′UTR of FEM1B using the CRISPR-Cas9 system. Generation of homozygous clones proved to be a challenging task. Our first challenge was selecting a pair of sgRNAs that could cut efficiently with minimal off target effects. Secondly, I initially obtained only heterozygous clones instead of the desired homozygous ones. To address this, I decided to sort GFP-positive cells that were highly fluorescent, thereby increasing the likelihood of obtaining homozygous clones, as higher fluorescence indicates a greater entry of CRISPR-Cas9 machinery into the nucleus. This optimization successfully enabled us to generate homozygous clones in both HeLa and MDA-MB-231 cells.
When doing the research, did you have a particular result or ‘eureka’ moment that has stuck with you?
Back-to-back eureka moments occurred during this project. First, we discovered that the FEM1B undergoes stop codon readthrough. Second, we observed that cancer cells with defective FEM1B readthrough were proliferating more slowly than parental wild-type cells.
Why did you choose Journal of Cell Science for your paper?
We chose Journal of Cell Science because it is one of the most reputable journals in the field of cell biology, renowned for publishing high-quality and impactful articles. Our work aligns well with the themes and focus areas of JCS, making it an ideal platform to share our findings with the scientific community. Additionally, JCS helps scientists gain recognition and advance in their careers by providing opportunities for first authors to promote their work.
The stop codon readthrough of FEM1B regulates cancer progression. The growth of xenograft tumours formed by wild-type (WT) and FEM1B readthrough defective cells (Δ3′UTR) HeLa cells. For details, see main paper.
The stop codon readthrough of FEM1B regulates cancer progression. The growth of xenograft tumours formed by wild-type (WT) and FEM1B readthrough defective cells (Δ3′UTR) HeLa cells. For details, see main paper.
Have you had any significant mentors who have helped you beyond supervision in the lab? How was their guidance special?
My PI, Prof. Sandeep Eswarappa, who believed in me throughout this project. It wouldn't have been possible without his support and guidance. His effort and patience have been incredibly motivating, constantly pushing me to achieve my best. Next, I want to acknowledge all the lab members and other colleagues from whom I have learned numerous techniques that were crucial for this research.
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?
During my school days, I was deeply fascinated by people doing research in laboratories and making discoveries. The idea of exploring the unknown and contributing to the advancement of science captivated my imagination. I also had a habit of constantly asking questions and seeking to understand the reason behind various phenomena. Watching scientists unravel the mysteries of nature and finding innovative solutions to complex problems inspired me immensely. This has greatly motivated me to pursue a career in scientific research.
Who are your role models in science? Why?
My role model is my dearest mother. She always pushed me to study, even when I felt like giving up during my school days. I owe everything I am today to her. While studying far from home, she never burdened me with her troubles, ensuring I could focus entirely on my education. I am incredibly indebted to her dedication, selflessness and unwavering support.
What's next for you?
As I will soon be finishing my PhD, I have begun searching for postdoctoral positions in reputable labs where I can continue to excel and advance my research career. I am eager to join a dynamic and innovative research team that will allow me to develop my skills further, collaborate with scientists and contribute to discoveries in my field.
Tell us something interesting about yourself that wouldn't be on your CV
I love exploring new places, talking to strangers and immersing myself in different cultures. Trying out delicious new food is one of my favourite activities. I love playing badminton, which keeps me active and energized.
Md Noor Akhtar's contact details: Department of Biochemistry, Indian Institute of Science, Bangalore, India.
E-mail: [email protected]
