HMS Virology

Virology Faculty Member - Ann Hochschild

Ann Hochschild

Maude and Lillian Presley Professor of Microbiology
Head of the Department of Microbiology
Harvard Medical School

Harvard Medical School
HIM Building, Room 1027
4 Blackfan Circle
Boston, MA 02115
Tel: 617-432-1986
Fax: 617-432-4787
Email: ahochschild@hms.harvard.edu
Visit my lab page here.



Our laboratory uses bacteria to study fundamental mechanisms of transcription regulation, as well as the biology of prions. With an emphasis on the development of genetic tools, our work also encompasses biochemical, structural and microscopy-based approaches.

Several projects in the lab are focused on prions and protein-based heredity. Prions are infectious, self-propagating protein aggregates that are notorious for causing devastating neurodegenerative diseases in mammals. They have also been described in fungi, where they act as protein-based genetic elements. Despite the apparent conservation of prions in evolutionarily divergent members of the fungal Kingdom, prions were not known to exist in bacteria. Having first demonstrated that E. coli cells have the requisite molecular machinery to propagate a model yeast prion, we recently uncovered two bacterial prion-forming proteins, the transcription termination factor Rho of Clostridium botulinum and the single-stranded DNA-binding protein SSB from Campylobacter hominis. At the same time, we have developed a set of genetic tools for detecting the conformational transitions that are diagnostic of prion formation. The identification of bacterial proteins with the abilities to form heritable prions points to a previously unrecognized source of epigenetic diversity in bacteria, and current work is directed at investigating the scope and significance of prion-like phenomena in bacteria.

We also have a long-standing interest in the transcription machinery and in transcription regulatory mechanisms. The RNA polymerase (RNAP) core enzyme is evolutionarily conserved from bacteria to man, as has been strikingly confirmed by crystallographic studies. Accordingly, insights into the function of the bacterial enzyme are likely to be relevant to the function of all multi-subunit RNAPs. Current work is focused particularly on regulatory mechanisms that target post-initiation stages of the transcription cycle, and specifically on factor-dependent transcription pausing, using genome-wide approaches. During the course of our transcription studies, we have developed a number of broadly applicable genetic assays for studying protein-protein interactions, including a widely used transcription-based bacterial two-hybrid assay that has facilitated a variety of projects in the lab.



Last Update: 8/10/2020



Publications

For a complete listing of publications click here.

 


 

Garrity S, Sivanathan V, Dong J, Lindquist S, Hochschild A. Conversion of a yeast prion into an infectious form in bacteria. Proc Natl Acad Sci USA 2010; 107:10596-601.

Yuan AH, Garrity SJ, Nako E, Hochschild A. Prion propagation can occur in a prokaryote and requires the ClpB chaperone. Elife 2014; 3:e02949.

Yuan AH, Hochschild A. A bacterial global regulator forms a prion. Science 2017; 355:198-201.

McPartland L, Heller DM, Eisenberg DS, Hochschild A*, Sawaya MR*. Atomic Insights into the genesis of cellular filaments by globular proteins. Nature Structural and Molecular Biology 2018; 25:705-714.
*Co-corresponding authors

Fleming E. Yuan AH, Heller DM, Hochschild A. A bacteria-based genetic assay detects prion formation. Proc Natl Acad Sci USA 2019; 116:4605-4610



© 2016 President and Fellows
of Harvard College