Lanny Ling photo
Contact Info
Office: 2202C Microbiology Bldg
Lab: 2202 Microbiology Bldg
Phone: 301-405-1035
Jiqiang (Lanny) Ling
Asssociate Professor

Teaching

  • Microbial Physiology (BSCI443)
  • Gene Expression (CBMG688F)

Graduate Program Affiliations

  • BISI-Molecular & Cellular Biology (MOCB)

Jason Yu, Parker Murphy, Hong Zhang, Cierra Wilson, Zhihui Lyu, Lanny Ling
(Left-right) Jason Yu, Parker Murphy, Hong Zhang, Cierra Wilson, Zhihui Lyu, Lanny Ling

Research Interests

Protein synthesis is a central process in all cells, and the protein synthesis machinery has been a major target for antibiotics. The rise of multidrug-resistant bacteria and a shortage of new antibiotics demand further studies of the protein synthesis machinery and the mechanisms of antibiotic resistance. Defects during protein synthesis in humans also lead to developmental and neurological diseases, yet the disease-causing mechanisms remain largely unclear. The overall goal of our laboratory is to understand the molecular basis of protein synthesis and its disease connection.  We are combining biochemical, single-cell, genetic, genomic, and proteomic approaches to study the following research areas:

defects in protein synthesis
Defects in protein synthesis. (A) Normal aaRSs active in aminoacylation and editing provide the ribosome with correct aa-tRNAs to allow robust and accurate translation. In addition to the correct amino acids (e.g., Ala for AlaRS), many aaRSs misacylate similar amino acids and require editing to remove the mistakes. The ribosome maintains fidelity through substrate selection and kinetic proofreading. (B) Defects in aminoacylation, aaRS editing, ribosome biogenesis, or ribosomal fidelity may decrease the efficiency and accuracy of translation, affecting various cell functions, bacteria-host interactions, stress responses, etc. Created with BioRender. 

1. The impact of translational defects in bacteria-host Interactions

Protein mistranslation (reduced translational fidelity) has been shown to cause growth defects in bacteria, mitochondrial dysfunction in yeast, and neurodegeneration in mammals. However, the role of translational fidelity during pathogen-host interaction is poorly understood. We have recently shown that optimal translational fidelity is critical for Salmonella to invade host cells. We are currently exploring the mechanisms by which translational fidelity and ribosome assembly affect host interactions, motility, stress responses, and antibiotic tolerance using systems biology and single-cell approaches. 

model for role of translational fidelity in bacteria-host interaction
Model for role of translational fidelity in bacteria-host interaction. Translational fidelity is heterogeneous among single cells. Bacterial cells with optimal translational fidelity are selected to enter host cells. Translational fidelity is further altered by the host environment to promote adaptation.

2. Translation and phenotypic heterogeneity among single cells

Phenotypic heterogeneity among genetically identical bacterial cells is critical for adaptation to the changing environment and leads to tolerance to antibiotics and stresses. We have shown that translational fidelity and ribosomal RNA expression are heterogeneous and sensitive to the fluctuation of the cellular cyclic AMP level. We are interested in understanding how fluctuations in translation arise and affect phenotypic heterogeneity.  

regulation of translation by cAMP
Regulation of translation by cAMP. cAMP promotes amino acid (AA) catabolism and ATP synthesis, increasing transcription of rRNAs and tRNAs. A high aa-tRNA level increases stop-codon readthrough by outcompeting release factors. 

3. Protein Synthesis Defects in Eukaryotes and Human Diseases

Recent advances in genome sequencing and genetics have led to rapid growth of identified mutations in aaRSs and ribosomal proteins that cause human diseases. We are currently using yeast and worm models to understand how translational defects affect stress responses, fitness, and aging. 


Education

  • Ph.D., The Ohio State University, 2008

All Publications

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