My research interests:
- Molecular phylogenetics
- How natural selection and mutation shape the translation machinery to optimize translation initiation, elongation and termination and how diverse lineages from viruses to mammals achieve efficient translation initiation with different types of adaptations
- Evolution of alternative splicing: mechanism and regulation
- Molecular adaptation in extreme environments
- Molecular coevolution, e.g., between host and parasite, between interacting protein partners, between mRNA and translation machinery, etc.
- Bioinformatic software development
My favourite creatures:
- Prokaryotic species, especially eubacterial species
- Unicellular eukaryotes, especially yeasts
- Eukaryotic model organisms
My lab equipment for data collection and analysis:
- Software such as DAMBE
- Public databases (e.g., those hosted in NCBI)
- Human brains (mine included, which is in urgent need of an upgrade)
A sample of research questions:
- What determines exon skipping? Do skipped exons have weak splice signals? What constitute splice signals? How spliceosome decode such signals? What is the most efficient splice signal in Baker's yeast? What is the best way (experimental and bioinformatic) to measure splicing signal strength? What determines alternative splicing in different cell types?
- What is the most efficient translation initiation signal? Does the small subunit ribosome do the scanning for the start codon or can a fully formed ribosome scan for start codon, too? When to scan from the 5' end and when to scan from the middle of 5'UTR (internal ribosomal entry)? If secondary structure embedding start codon (or Shine-Dalgarno sequence or Kozak consensus) can obscure the translation initiation signal, how would highly expressed genes avoid this? What is the best way of measuring gene expression experimentally or bioinformatically? Do translation initiation efficiency affect elongation efficiency/accuracy? How to measure translation elongation efficiency/accuracy? Will a few closely spaced minor codons severely affect translation elongation? What is the optimal translation stop signal? How do release factors decode the stop signal? How the relative concentration and decoding capacity of different release factors affect stop codon usage? How frequent do tRNAs misread stop codons or release factors misread sense codons? How will these factors affect stop codon usage?
- How do genes, gene interactions and molecular mechanisms change over time? How to trace the evolutionary history back to billions of years? How to map evolutionary events such as speciation, gene duplication, neofunctionalization and subfunctionalization of duplicated genes, etc., to the reconstructed phylogeny? How can we improve our resolution of deep phylogenies?
- How do organisms adapt to extreme environment such as Helicobacter pylori to the acidic mammalian stomach? Does it involve only a few genes organized in a module (e.g., an operon) or does it involve the change of many genes and regulatory networks?
- How species interact and co-evolve? How do bacteriophage adapt to their bacterial hosts? What happens after host-switching?
- What bioinformatic software do biomedical researchers need? How to develop new bioinformatic tools to facilitate their research?