Research

My research interests:

1. Molecular coevolution between signals and their decoders: Sense codons are decoded by tRNAs, stop codons by release factors, Shine-Delgarno (SD) sequences in bacterial mRNAs by the anti-SD sequences at the 3' end of the small subunit ribosomal RNA, splicing sites by spliceosomes, replication origin signals by dnaA proteins in bacteria and ORC proteins in Archaea and Eukaryota, and so on. How would the signals and decoders evolve to adapt to each other to increase the efficiency of cellular processes and enhance organismal fitness?
2. Molecular phylogenetics and phylogeography: How has biodiversity originated, evolved, migrated, and colonized new environments through gaining, losing, or modification of genes and their functions? How does gene duplication and horizontal gene transfer contribute to organismal adaptation? How is biodiversity distributed over space and time? How have mutation and selection, mediated by environmental differences, shaped the temporal and spatial distribution of biodiversity? How to characterize biodiversity in nature using phylogenetic and phylogeographic methods? How to improve phylogenetic and phylogeographic methods? How do pathogens and hosts coevolve?
3. Bioinformatic software development: We create computational tools to facilitate the analysis of genomes, transcriptomes, and proteomes to understand cellular processes such as gene expression, RNA splicing, translation, cell replication, and their regulation and optimization.

My favourite creatures:

1. Viruses
2. Prokaryotic species, especially eubacterial species
3. Unicellular eukaryotes, especially yeasts
4. Mitochondria
5. Eukaryotic model organisms

My lab equipment for data collection and analysis:

1. Computers
2. Software such as DAMBE
3. Public databases (e.g., those hosted in NCBI), BOLD, etc.
4. 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 constitutes splice signals? How does the 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 the 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? Does 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 do the relative concentration and decoding capacity of different release factors affect stop codon usage? How frequently 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 an 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 do interact and co-evolve? How do bacteriophages 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?