Methodological tour-de-force: Biochemist Annita Louloupi receives Marthe Vogt Award
Award-winning doctoral thesis has been completed at the MPI for Molecular Genetics
DNA (deoxyribonucleic acid) carries the genetic instructions for the development and growth of all known organisms. In order for these “instructions” (genes) to be converted into a functional product, the DNA is first copied – or transcribed – into RNA (ribonucleic acid). Similar to DNA, RNA consists of four different nucleotides whose sequence encodes the genes. The sequence that codes the functional product (exons) is interrupted by non-coding regions (introns); these introns are also transcribed. Next, during a process called RNA splicing, the introns are carefully removed, leaving only the exons to be later translated into the functional product – proteins. This process is an important and highly regulated step during gene expression.
RNA nucleotides can be biochemically modified during their life cycle. Although such modifications do not alter the genetic information carried by RNA, they can affect its functionality. In her doctoral research, Annita Louloupi studied one of the most widespread RNA modifications, m6A, a methylation that occurs at the N6-position of adenosine. Her main goal was to understand how m6A regulates RNA splicing and, more specifically, the rate of splicing.
The challenge facing Annita Louloupi at the beginning of her doctoral work was to develop new analytical techniques that would be accurate and sensitive enough to detect m6A-modified RNA during its brief “nascent” state, i.e. during the short phase immediately after transcription yet before RNA undergoes RNA splicing. “My questions have driven my methods,” stated the biochemist, describing her approach. By combining several of these techniques, Annita Louloupi was able to gain new insights on the role of m6A modification in RNA splicing kinetics. When put onto a specific region within the “nascent” RNA, the m6A acts as a “fast-track ticket” in the processing queue – RNA with such a ticket will develop into “mature” functional RNA faster than that without a ticket.
RNA modifications have been linked to several diseases, including cancer, cardiovascular diseases, genetic birth defects, metabolic diseases, neurological disorders, and viral infections. The methodology that Annita Louloupi developed provides a valuable toolkit for other molecular biologists, as it can be adapted or directly applied in different cancer cell lines, cells going through differentiation, virus infections, and/or treatments.
In January 2019, while still completing her dissertation, Annita Louloupi started her postdoctoral research in the Computational Regulatory Genomics Laboratory at the Berlin Institute for Medical Systems Biology (BIMSB), which is part of the Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC). Currently, she is involved in multiple different projects that revolve around post-transcriptional gene regulation. “It’s been a hectic and stressful year, and I am very grateful for this award because it has given me an opportunity to pause and reflect back on my doctoral work and appreciate the things I have accomplished.”