The laboratory is interested in the greater understanding of RNA processing mechanisms and how they can be used as tools for biotechnology. Bigger questions involve how transcripts are modified by numerous processing steps, coordination between organelle and nuclear genomes, and RNA/protein interactions. Currently we are investigating engineered specificity and biochemical mechanisms of C-to-U and U-to-C RNA editing tools.
RNA transcripts are critical subjects of regulation since they are the informational intermediaries between DNA and protein. Mutations in DNA could theoretically be repaired at the RNA level, transcripts can be stabilized by RNA binding proteins, and transcripts can be destroyed altering the expression of proteins. Discovering or engineering new tools of RNA regulation can help treat disease or improve agriculture.
The world's human population is projected to grow from 7.5 billion to over 11.2 billion by 2100. This will put pressure on a food production system reliant on fossil fuels for a majority of its nitrogen. At current levels of production over-fertilization problems have led to eutrophic waters incapable of life downstream of major agricultural fields. Improvement of crops primary productivity through photosynthesis might allow increased crop production and reduced environmental damage in line with the Borlaug hypothesis.
We are investigating RNA processing mechanisms to provide new tools to treat diseases and improve agriculture. In particularly we are interested in RNA editing. RNA editing mechanisms are critical for photosynthesis, aerobic respiration, neural transmission, lipid metabolism, and viral defense in humans and plants. RNA editing mechanisms might be rationally engineered to make specific nucleotide changes in organisms to fix problematic mutations causing disease or lead to improved functions.
C-to-U RNA editing in plants is required for photosynthetic function and is performed by a large complex with several members from various protein families. One large class of nuclear encoded proteins involved in controlling organelle expression present in most eukaryotes is the pentatricopeptide repeat (PPR) family of proteins. PPR proteins bind single-stranded RNA through a sequence specific mechanism. PPR proteins have been linked to C-to-U and U-to-C RNA editing, RNA maturation, splicing, RNA turnover, and translation. Since PPR proteins have such diverse functions, we are investigating how they alter transcripts. This could lead to new tools useful for the manipulation of RNAs.