Maria Barna (Stanford Univ.)
May 15, 2019 -
12:00 pm to 1:00 pm
Thomas Laboratory 003
Maria Barna is an Assistant Professor in the Departments of Developmental Biology and Genetics at Stanford University. Dr. Barna obtained her B.A. in Anthropology from New York University and her Ph.D. from Cornell University, Weill Graduate School of Medicine. She completed her thesis work in the lab of Dr. Lee Niswander in the Developmental Biology Department at Sloan Kettering Institute in 2007. Dr. Barna was subsequently appointed as a UCSF Fellow through the Sandler Fellows program, which enables exceptionally promising young scientists to establish independent research programs immediately following graduate school. In 2013, she received a dual appointment as an Assistant Professor in the Departments of Developmental Biology and Genetics at Stanford University. Dr. Barna has received a number of distinctions including being named a Pew Scholar, Alfred P. Sloan Research Fellow, and top ’40 under 40’ by the Cell Journal. She has received the Basil O’ Connor Scholar Research Award and the NIH Directors New Innovator Award. In 2016, she was the recipient of the Rosalind Franklin Young Investigator Award, an award given to two female scientist in the world every three years in the field of genetics and the American Society for Cell Biology Emerging Leader Prize. She has also received the H.W. Mossman Award in Developmental Biology and the Tsuneko and Reiji Okazaki Award. She is presently a NYSCF Robertson Stem Cell Investigator.
Ribosomes in Gene Regulation: Controlling the diversity of proteins that can be produced in specific cells, tissues & organisms
In the transmission of biological information, the ribosome has been perceived to serve an integral but largely passive participant in the synthesis of all proteins across all kingdoms of life. Our research has changed this view, by demonstrating that not all of the millions of ribosomes within each cell are the same and that ribosome heterogeneity provides a novel means for diversity of the proteins that can be produced in specific cells, tissues, and organisms. I will present our work centered on developing a roadmap for the characterization of ribosome composition at a single cell level and during cellular differentiation. We employed a highly quantitative mass spectrometry-based approach to precisely quantify the abundance of each ribosomal protein (RP) as well as a large cohort of ~ 400 ribosome associating proteins (RAPs) belonging to actively translating ribosomes. This led to the identification of subsets of ribosomes that are heterogeneous for RP composition. To further address the functional role of ribosome heterogeneity in translational control of the mammalian genome, we employed CRISPR/Cas9 to endogenously tag and purify heterogeneous ribosome populations. We then developed an adapted ribosome profiling method to precisely quantify and characterize the nature of mRNAs translated by distinct heterogenous ribosomes genome-wide. This led to the identification of subpools of transcripts, critical for key cellular processes including cell signaling, metabolism, growth, proliferation and survival, which are selectively translated by specific types of ribosomes. Most interestingly, there are specific signaling pathways where almost every single component is selectively translated by specialized ribosomes demarcated by a single RP. I will further present recent findings on the mechanisms by which ribosome-mediated control of gene expression is encoded by structured RNA elements within 5’UTRs visualized through Cryo-EM. Together, these studies reveal a critical link between ribosome heterogeneity and specialized translational control of the mammalian genome, which adds an important layer of control to the post-transcriptional circuitry of gene regulation.
Free and open to the university community and the public.
Ricardo Mallarino, Department of Molecular Biology