The RNA Institute
Mass Spectrometry Center
The RNA Institute Mass Spectrometry (MS) Center is dedicated to the development of MS-based technologies for investigating the structure-function relationships of natural and synthetic RNA as tools for drug discovery. Consistent with the mission of The RNA Institute, the unique collection of modern instruments, and enabling technologies developed by Dan Fabris at the MS Center will be utilized in full-fledged collaborations with colleagues who have projects aimed at reaching a greater understanding of the role of non-coding RNA in gene regulation and viral replication. These insights will lead to the identification of possible targets for early drug discovery operations that could produce new treatments for orphan diseases and alternative drugs for resistant strains responsible for infectious diseases.
Novel Mass Spectrometry technologies and state of the art instruments
Mass Spectrometry (MS) has the versatility necessary to accomplish the elucidation of the structure-function relationships of biologically relevant RNA and associated proteins. New methods for evaluating the ability of small molecule ligands to affect the structure of RNA substrates, to modulate their binding properties, and ultimately to influence their biological and pharmacologic activities are currently under development. Strategies combining footprinting and crosslinking reagents with MS detection, collectively known as MS3D, have been devised to pursue the 3D structure determination of RNA and ribonucleoprotein complexes that are not readily amenable to traditional high-resolution techniques. New technologies are being developed for sensitive analysis of RNA adducts with extremely low copy-number to enable discovery of rare modifications and for in vivo structural determination of targets immersed in their natural cellular environment.
These efforts are supported by state of the art instrumentation at The RNA Institute:
- A 12 Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer for ultra high-resolution characterization of large protein-RNA complexes involved in gene regulation and viral replication processes
- An Orbitrap mass spectrometer for high-resolution determination of protein-RNA crosslinks capable of revealing the identity of cellular factors involved in RNA-mediated functions
- An ion mobility spectroscopy (IMS) mass spectrometer for investigating the effects of small molecule ligands as possible drug candidates on the conformation of target protein-RNA complexes
- A quadrupole-time of flight (Q-TOF) instrument interfaced with a nanoflow high performance liquid chromatography (nanoLC) system for sensitive detection of low copy number RNA modifications