What is RNA?
RNA is the central intermediate required for life. It serves many functions. One is as a messenger. RNA facilitates an indispensable role as a go between that delivers information encoded by your genetic blueprints made to DNA to sites of protein manufacturing called ribosomes.
In the early 60s, experiments conducted in mice demonstrated that inhibition of the decoding of messenger RNA by the ribosome disrupted memory. Recent work has illuminated similar mechanisms are required for persistent changes in the activity of sensory neurons tasked with the detection of pain.
Our Goal
Our goal is to understand how RNAs are controlled in sensory neurons with the goal of disrupting the normal series of events that promotes chronic pain. By blocking pain at or near its origin, we hope to identify non-opiate strategies to improve patient care.
Our Areas of Investigation
Problem 1 – How is the landscape of nascent translation controlled in sensory neurons?
Pain is an unpleasant but essential sensation. It can promote behaviors that protect us from additional tissue damage and injury. On a cellular level, pain generally originates in sensory neurons called nociceptors. Noxious stimuli trigger rapid increases in cap-dependent translation in nociceptors. The specificity of local translation is governed by regulatory factors and mRNAs that collaborate to ensure precise temporal and spatial control of protein synthesis. We are interested in understanding which mRNA/protein complexes play critical roles in this process. We make use of pharmacology and genetics to identify proteins required for acute and chronic nociceptive pain.
Problem 2 – Which mRNAs need to be translated for persistent changes in neuronal activity to occur?
Neurons must modulate their function in response to a range of physiologic stimuli. A key mechanism that facilitates rapid changes in sensory fibers is local translation from localized mRNAs. Local translation serves a key biological function. Neuronal protein synthesis can occur in the soma, synapse, or in axons. In nociceptors, axons can span vast distances (in some cases a meter or longer). Local translation provides a means to accomplish protein biosynthesis at the site where polypeptides are required. This provides a rapid solution to the problem of generating new proteins on demand that can guide critical processes to the function of afferent fibers. We are interested in identifying mRNAs whose translation regulates neuronal activity.
Problem 3 – How are RNAs recognized by RNA-binding proteins?
The untranslated regions of mRNA are resplendent with regulatory information. Regulatory elements are decoded by RNA-binding factors (protein and RNA) that can directly associate with mRNA. Specificity of these factors for RNA is fundamentally important as binding is a prerequisite for all subsequent regulation. We employ functional genomics to profile the specificity of individual proteins and larger protein complexes using custom approaches. We are broadly interested in understanding the physiologic significance of RNA-protein interactions in vivo.