The lab of Yimon Aye (EPFL) invites you to the next Chemical Biology e-seminar, with Prof. Dr. Sarah Slavoff, from the Yale University, on the “Dark Matter of the Human Genome”. The talk will take place online on Tuesday, September 28th 2021, 16:15.
About the talk
Advanced methods in next-generation sequencing and proteogenomics have revealed thousands of previously invisible human genes, increasing the known size of the human genome by at least 10%. This previously unannotated “dark matter” of the human genome includes small open reading frames (smORFs) encoding polypeptides of fewer than 100 amino acids, and alternative open reading frames (alt-ORFs) encoding proteins 100 amino acids or larger. Sm/alt-ORFs previously escaped detection due to their short lengths, overlap with annotated protein coding sequences in different reading frames, and/or initiation with non-AUG start codons. Recent studies have shown that hundreds of smORFs are required for cell growth and survival, and some smORF-encoded polypeptides (SEPs) bind to and regulate the activity of macromolecular complexes involved in critical cellular processes and disease. However, key questions about SEP modifications, detection, and functions remain. My research group is developing advanced mass spectrometry proteomics-based approaches to answer each of these questions, and in this presentation, I will describe (1) proteomic discovery of alt-RPL36, which overlaps the coding sequence for human ribosomal protein L36 and binds to TMEM24 to regulate PI3K/AKT/mTOR pathway signaling, and (2) identification of phosphorylation sites on the NBDY SEP that control membraneless organelle dynamics. Taken together, these findings demonstrate that interfacing phosphoproteomics, interactomics and chemoproteomics with proteogenomics can drive forward our understanding of the cellular functions of recently discovered sm/alt-ORF-encoded polypeptides and proteins.
About Sarah Svaloff
Sarah Slavoff received her Bachelor’s degree in Biochemistry from the University of Maryland, College Park, followed by Ph.D. studies at MIT with Professor Alice Ting during which she developed new technologies for enzyme-mediated protein bioconjugation. Sarah’s postdoctoral fellowship with Alan Saghatelian at Harvard University resulted in the first proteomic technology for large-scale detection of previously invisible polypeptides expressed in human cells, which are now known to number at least in the thousands. Sarah started her independent research group at Yale in 2014, and was promoted to Associate Professor in 2021. Her research program focuses on advanced (chemo)proteomic technologies to detect and characterize human polypeptide-encoding genes. She has been recognized with a Searle Scholar Award and a Yale Arthur Greer Memorial Prize for Scholarly Research.