Our Research
The vast majority of human genes are transcribed into RNAs but do not encode for proteins, a discovery that has revolutionized our understanding of cell biology to include roles of non-coding RNAs in every aspect of cell function. The question of when and where a particular RNA localizes within the cell is closely related to its function. Critically, many disease states are associated with RNA mis-localization. To dissect subcellular dynamics of biomolecules including RNA, live cell fluorescence microscopy offers precise insights with single cell and even single molecule resolution.
Our research program addresses the fundamental question:
How do localization and dynamics of RNAs in live cells contribute to cell function in health and disease?
Illuminating RNAs with live cell sensors
Unlike fluorescent proteins, no fluorescent RNAs have been discovered in nature. Therefore, RNAs are engineered to include fluorescent markers for tagging and tracking of RNAs in live cells. The diversity of RNA species in nature and the complex behavior in cells requires complementary approaches for a truly comprehensive toolbox that captures RNA biology in live cells. We develop and adapt tools for RNA imaging in live cells, guided by needs to visualize RNAs in our biological systems of interest.
Protein (green) and RNA (pink) labeling in live mammalian cells
Braselmann et al, Nat. Chem. Bio., 2018
Mammalian cells (yellow) infected with Listeria (pink)
Batan, Braselmann et al, Biophys. J., 2018
RNA dynamics at the host-pathogen interface
Infection of mammalian cells with intracellular bacterial pathogens acutely perturbs cellular processes to establish pathogen growth and dissemination within the body. Our model system is Listeria monocytogenes, the third leading cause of death from food poisoning in the United States (CDC). Listeria infection affects fundamental aspects of host RNA biology, including mRNA processing. We investigate subcellular dynamics of RNAs, proteins and bacteria in infected mammalian cells live. We are interested in both coding and non-coding RNAs, necessitating multiplexed tagging and tracking platforms to illuminate different RNA species simultaneously. Live cell fluorescence microscopy reveals insights in underlying biochemical processes while capturing heterogeneous dynamics on the single cell level.
Our Funding
Georgetown University
NIH 4R00GM127752-03
Luce Foundation