Ribosomes are at the center of gene expression regulation. Not only do they synthesize proteins, but they regulate transcription and respond to stress signals. The translational control underlies the pathogenesis of infectious and genetic diseases. Translation is a key antibiotic target, but the emergence of antibiotic resistance poses a serious challenge in the fight against infectious diseases. To improve our understanding of the translational control of gene expression in molecular detail, we propose to elucidate the structural mechanisms of (1) translation initiation of viral mRNAs and virus-like cellular mRNAs; (2) bacterial stress responses which couple translation with transcription, conferring bacterial pathogenicity and antibiotic resistance and (3) translation elongation and termination. Understanding these mechanisms may enable discovery of novel drugs for the treatment of viral or bacterial infections or genetic diseases caused by nonsense mutations.

Public Health Relevance

Ribosomes are at the center of gene expression regulation in all organisms. We will elucidate structural mechanisms of translation regulation during viral or bacterial infection, as well as genetic diseases. Understanding these mechanisms may enable discovery of novel drugs for the treatment of infectious diseases or genetic diseases caused by stop-codon mutations.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Unknown (R35)
Project #
5R35GM127094-03
Application #
9923681
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Reddy, Michael K
Project Start
2018-05-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Genetics
Type
Schools of Medicine
DUNS #
603847393
City
Worcester
State
MA
Country
United States
Zip Code
01655