Alexander S Mankin
University of Illinois Chicago, IL·Microbiology & Immunology
Every cell builds its proteins on the ribosome, a molecular machine that reads a genetic message and links amino acids into a chain. In bacteria, this process is a favored target for antibiotics, so understanding exactly how it works — and where it can be jammed — matters for treating infections that no longer respond to existing drugs.
- Fields
Microbiology & Immunology
Biochemistry
Pharmacology
- Topics
ribosome
translation
protein synthesis
- Grants
- 4 known grants, through Dec 2028
What they work on
- Optimize small-molecule inhibitors of peptidyl-tRNA hydrolase, the bacterial enzyme that recycles unfinished protein chains, by synthesizing derivatives of sub-micromolar hits for stronger activity against the Klebsiella pneumoniae enzyme and better uptake into cells.
- Map how candidate inhibitors bind peptidyl-tRNA hydrolase using surface plasmon resonance and X-ray crystallography, and determine their cellular targets, effects on protein synthesis and the resistance mechanisms bacteria can use against them.
- Identify apidaecin variants with improved action on ribosomes from Gram-negative and Gram-positive pathogens by expressing tunable libraries of peptide genes inside bacterial cells.
- Expand the range of bacteria apidaecin-like peptides can kill by engineering variants that no longer require the SbmA transporter to enter cells.
- Determine how drosocin, a proline-rich peptide from fruit flies, binds the ribosome and blocks translation termination, using X-ray structures of ribosome–peptide complexes and comparison with apidaecin.
- Map where auxiliary translation factors are recruited to ribosomes across the bacterial genome using crosslinking-based ribosome profiling (XLRibo-seq) to reveal which sequences need their help.
- Dissect the mechanisms of the translation factors LepA, EttA, BirA and HflX on selected problematic gene models in vitro, then test the inferred mechanisms in cells with designed reporters and mutant strains.
- Build iRibo-T, a ribosome with messenger RNA covalently fused to its ribosomal RNA so it translates only one message, and use it to improve production of lysine-rich proteins that normal bacterial ribosomes translate poorly.
More about the research
Work in this lab spans four connected questions: how the ribosome copes with sequences that are hard to translate, how natural antibacterial peptides stop protein synthesis at an unusual step, how an essential bacterial recycling enzyme might be blocked by small molecules, and how a ribosome can be re-engineered to make one chosen protein.
Why it matters
Bacterial infections that resist current drugs need antibiotics with new mechanisms. Blocking peptidyl-tRNA hydrolase, an enzyme essential for bacterial growth with no known inhibitors, or improving bee- and fly-derived peptides that halt protein synthesis at its termination step, could yield leads for treating infections caused by pathogens such as Klebsiella pneumoniae. Clarifying how cells help ribosomes make difficult proteins may also inform diseases tied to faulty protein production, and the engineered single-message ribosome could make hard-to-produce therapeutic and industrial proteins more cheaply.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Unraveling context specificity of translation by elucidating the mechanism of action of auxiliary translation factors
NIH · Apr 2018 – Dec 2028
Engineering a fully-integrated translation system for production of proteins and peptides
NSF · Jun 2024 – May 2028
Identifying inhibitors of the bacterial peptidyl-tRNA hydrolase
NIH · Feb 2026 – Jan 2028
Closest labs
Matthieu Gagnon
University of Texas Medical Branch at Galveston, TX·Biochemistry
Determine how release factor 3 (RF3) releases protein chains from ribosomes that have made errors and helps protein folding during synthesis, using cryo-EM structures of bacterial 70S ribosome complexes.
Hong Jin
University of Illinois Urbana-Champaign, IL·Biochemistry
Determine how the conserved GTPase Drg affects paused ribosomes, using test-tube translation systems rebuilt from E. coli and yeast to probe the peptidyl transferase center and measure peptide bond formation rates.
Srinivasa Subramaniam
Florida Atlantic University, FL·Neuroscience
Identify the protein and RNA components on ribosomes that interact with mutant huntingtin (mHTT), the toxic protein that causes Huntington disease, using biochemical approaches.
The school
University of Illinois Chicago: 42 labs on PI Pages, $532M a year on research, 359 research doctorates a year.
Reach out
A start for your email. Fill in the brackets.