Work at the University of Maryland, Baltimore County
The Summers Lab | Mike Summers, PI
UMBC | Baltimore County, Maryland
Projects in the Summers lab:
Research in our laboratory is aimed at understanding how HIV-1 and other retroviruses assemble in infected cells and package their RNA genomes, and on the development of new NMR methods for studying large RNAs and protein-RNA complexes. In recent studies (in collaboration with the Telesnitsky laboratory) we found that HIV-1 RNA function and fate are controlled by heterogeneous transcriptional start site usage, in which 5′-capped RNAs transcribed with a single 5′-guanosine are selected for packaging and function as genomes (gRNA) whereas those transcribed with two or three 5ʹ-guanosines are retained in cells and function as mRNAs. How can transcriptional inclusion of a single 5′-guanosine influence the function and fate of a ~9-kilobase HIV-1 transcript? Our studies have revealed that: (1) RNAs transcribed with a single initial guanosine adopt a structure that sequesters the 5ʹ-cap and prevents binding by cap binding proteins. In contrast, capped transcripts that begin with two or three guanosines adopt structures that expose the 5ʹ-cap and enable interactions with cap binding proteins. (2) Cap sequestration is orchestrated by two conserved hairpins (Tar and polyA) and is a dominant negative determinant of packaging. (3) All RNA elements required for authentic packaging efficiency were identified. (4) We identified the initial nucleocapsid binding site, a potential Achilles’ Heel for RNA targeted antivirals. We are now poised to understand how the viral Gag protein assembles on the packaging signal, and we are looking to recruit students who are interested in working with us on this and related projects. ROHR students who join our group will with a small team of UMBC undergraduates and a graduate student or postdoc on one of several ongoing projects, including (i) NMR and EM studies of Gag assembly on the packaging signal, (ii) determining how cellular factors bind the viral mRNAs to promote splicing and translation, or (iii) developing fluorescence methods to study RNA structural changes in vitro and in cells that appear to occur during virus assembly and maturation. Students have the opportunity to participate in weekly lab meetings and present their findings at Summer Research Festival at the end of the summer research period. Outside-the-lab activities typically include a picnic with steaks and steamed Maryland crabs, mountain biking excursions, and hiking in local and historic state parks.