Craig Hunter, PhD
Professor
Department of Molecular and Cellular Biology, Faculty of Arts and Sciences
Biogenesis, Transport, and Function of intercellular RNAs
Understand how the silencing information of RNAi spreads among cells and transmits to the progeny; Investigate the function of intercellular RNA transporters in nematodes and mice and discover intercellular signaling RNAs.
Commercial Opportunities
A remarkable property of RNAi in the nematode C. elegans and in some other multicellular organisms is its systemic nature: silencing signals can cross cellular boundaries and spread between cells and tissues. Furthermore, C. elegans and some other organisms can also perform environmental RNAi: sequence-specific gene silencing in response to environmentally encountered dsRNA. This phenomenon has facilitated significant technological advances in diverse fields including functional genomics and agricultural pest control.
In biological research, intercellular spread of RNAi has served as a cheaper and simpler way to deliver dsRNA into cells and lower organisms than microinjections. This has led to major advances in RNAi screening in nematodes and cell lines.
In agriculture, work has already begun in utilizing environmental RNAi technology as a form of pest control. For example, dsRNAs that are lethal to specific insects can be expressed in plants; this strategy has been used for the Western corn rootworm and has the potential to be a widespread approach to be a safer method of pest control for crops.
In humans, the conserved members of the environmental RNAi family could be exploited to help fight disease. It is possible that therapeutics in the form of dsRNA could be delivered orally to humans via transgenic crops or genetically modified bacteria. This would be a novel approach to treating diseases for which traditional small molecules do not suffice. It has also been suggested that the RNAi machinery present in animals is there to serve as a defense against viruses, so understanding how it operates could allow us to improve our viral defenses.
Environmental RNAi silencing:
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Panels A and A’ show each cell in C. elegans expressing nuclear GFP, with A being wildtype and A’ being a sid-1 mutant. In B, an RNAi construct to silence GFP is expressed in the body wall muscle cells only (marked in red), however, all GFP is silenced. However, in panel B’, the only GFP that is silenced in the sid-1 mutant is in the red-positive body wall muscle cells themselves; the signal has not spread to the rest of the nematode. This shows that the RNAi signal in panel B was spread due to the presence of the SID-1 transporter. For more information, see Jose, et al., 2009. PNAS. 106(7):2283-8.
Current Research Interests
- Discovery and characterization of C. elegans genes essential for the spreading of the RNAi signal among cells.
- Characterize function of vertebrate homologues of RNA transport proteins identified in C. elegans.
- Defining the molecular features of nucleic acids that allow dsRNA-specific transport through SID-1 channels.
Tools and Assays
- Transcriptome comparisons
- Systems biology
- Regulatory network characterization
- RNAi screening
Research Expertise
Using the model organism Caenorhabditis elegans to examine several aspects of gene regulation, the Hunter laboratory seeks to understand how gene activity is controlled. One of the Hunter laboratory’s main interests is RNA interference (RNAi) and the way in which RNAi silencing signals are spread between cells and to progeny. The group uses the powerful genetics of C. elegans to identify genes required for the process and to implicitly characterize the activities of related mammalian homologues such as SID-1. They have provided a mechanistic basis for understanding how gene-specific information is communicated between cells. Furthermore, their findings will provide new means of introducing therapeutic dsRNA into cells by manipulating intercellular gene regulation.