Kieft Lab research interests - overview
RNA is the most versatile of all biological macromolecules. It can encode genetic information (like DNA) and also fold into complex structures essential for complicated biological functions (like proteins). Research in the Kieft Lab is seeks to understanding how the structures of viral RNA drive diverse function, motivated by the fact that: 1) Viral RNAs have evolved to perform myriad functions, often of amazing subtly and elegance, giving us a diverse set of RNAs to study. 2) Viruses remain a substantial human health threat and a detailed molecular understanding of them is required to develop new therapeutics. 3) Many viral RNAs manipulate the host cell’s machinery; by studying how this happens, we learn fundamental things about basic biological processes.
Our goal is to understand these RNAs and their function in detail. We are not satisfied to know that that a certain mutation in a specific RNA causes a loss of function, we want to know why. We ask questions such as: What is the architecture and the conformational dynamics of a certain folded RNA? What does the RNA interact with and how? What are the implications of these interactions? Do mutations alter the structure of the RNA? How? What does this mean in terms of function? Our approaches include cell culture-based methods with disease relevant cells, in vitro activity assays, biochemical studies, x-ray crystallography, biophysical methods like analytical ultracentrifugation and thermal denaturation, chemical probing, native gel electrophoresis, mass spectrometry, etc. We are also beginning to employ single-molecule FRET experiments (in collaboration with the lab of Ruben Gonzalez, Columbia Univ.) and hope to soon start cryo-EM studies.