Research in the Filbin Lab focuses on understanding the fundamental mechanisms of eukaryotic translation initiation and how these mechanisms are manipulated during viral infection as well as cellular development.
Non-coding RNA Structure-Function
Non-coding RNAs (ncRNAs) are essential players in biology; they form the core of important cellular machines, they decode genetic information, they regulate gene expression and they functionally and structurally manipulate other macromolecules. Considering their varied roles, ncRNAs come in many different varieties, including ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), micro RNAs (miRNAs) and a broad class of long non-coding RNAs (lncRNAs). The role of rRNA and tRNA is fairly well defined as is the processing and function of miRNAs. However, the role of lncRNAs is still a major question in RNA biology. We are particularly interested in the role of viral lncRNA structure during viral replication.
The family of lncRNAs we study are encoded in the 5′ and 3′ untranslated regions (UTRs) of viral genomic RNAs. These UTRs are capable of recruiting 80S ribosomes independent of the methylated guanosine cap structure found on the 5′ end of eukaryotic mRNAs, and often function in the absence of canonical translation initiation protein factors. Each virus has adapted to functionally replace the 5′ cap and host proteins factors via unique RNA structure-driven methods. By studying the structure-based mechanism of translation initiation, we aim to learn about fundamental mechanisms of eukaryotic translation initiation and the roles of lncRNAs in biology.
Translational Regulation in Developing Neurons
Protein synthesis is an indispensable yet energetically costly process within the cell. Considering this, translation is tightly coordinated with the condition of the cell. Both intra- and extracellular signals dictate when translation occurs as well as which proteins are produced based on current cellular needs. During cellular development, protein synthesis is spatiotemporally regulated to ensure proper tissue architecture formation. Yet, the ways in which translation machinery is regulated during cell development is not well defined. We are particularly interested in the mechanism of localized protein synthesis control during neuronal development.
Neurons are highly polarized cells that develop directionally in response to chemotropic factors in their surrounding environment. Part of this response involves translation regulation at axonal growth cones – an extension of the developing neuron that will eventually form a synapse. When chemoattractive cues are sensed, translation in growth cones commences to provide cytoskeletal proteins necessary for directional growth. The link between the extracellular cue and intracellular response is a transmembrane dependence receptor, DCC, which tethers translation machinery to the membrane until the extracellular signal is received. We are interested in how DCC binds to and releases translation machinery, and whether or not the machinery is primed to translate a message or initiate de novo protein synthesis once the extracellular signal is received. Much like the ncRNA project, these studies shed light on how protein machinery can be manipulated and hence furthers our understanding eukaryotic translation initiation mechanisms.
Research in our lab is performed in collaboration with the lab of Drs. Jeffrey S. Kieft and Kirk C. Hansen at the University of Colorado School of Medicine. We are always open to new collaborations to foster a rich experience for our undergraduates as well as continue exciting research. Please contact us if you are interested in a joint project!