New Faculty II
$1 725 830
Statement of Benefit to California:
This is a proposal to identify factors that induce neuronal differentiation of stem cells, using planarians as a model organism of regeneration, tissue homeostasis and stem cell biology. Planarian flatworms maintain a population of pluripotent stem cells throughout life that are capable of replacing the central nervous system (CNS). The investigator plans to generate antibodies that recognize planarian neural proteins that are conserved in humans, and proposes to use these antibodies to monitor the differentiation of stem cells into mature neurons during regeneration. S/he will then use microarray platforms to differentially analyze genes expressed at various stages of differentiation, followed by high throughput whole mount in situ hybridization analysis screens for tissue-specific expression of target genes. Finally, the applicant will use inhibitory RNA to knock down the expression of conserved genes, in order to assess the effect of these genes on neurogenesis. Reviewers were very supportive of this new principal investigator with a novel and unusual proposal. Employing stem cells to replace lost tissue in human CNS disease and injury will require a careful understanding of the signaling factors required for neuronal differentiation of stem cells, and a great deal of exciting information might be gleaned from this creative proposal utilizing an intriguing and surprisingly under-explored model organism. The major potential limitation to the work is the extent to which specific molecular targets from the flatworms will be applicable to humans. This is always a risk when working with lower species, but reviewers commented that the phenomenon of limb and CNS regeneration is biologically remarkable and worthwhile of in-depth study. The research proposal was judged as logical, carefully thought-out, and impeccably written. The applicant provides extensive preliminary data of excellent quality, and considerable attention is given to controls, potential pitfalls, and alternative approaches. Reviewers noted that planarian worms are a good model system for these screening experiments: they are easy to manipulate genetically and they can be maintained in high numbers at relatively low cost. As an example of the power of the approach, reviewers noted that the applicant estimates that his group could screen 1000 genes within 3-6 months of each microarray screen. The applicant is a promising new investigator with good training and a high-quality publication record, and seems well-placed to be able to achieve the goals outlined in the proposal. S/he has extensive expertise in all facets of this work, particularly in the planarian flatworm model and in developing tools for gene analysis and regeneration. The proposal includes a general career development plan and identifies two prominent mentors. Reviewers also supported the applicant’s plans to reach out to other academic institutions for collaborations and mentorship. The institution has a strong biology program and was enthusiastic in support of the applicant. The institution has provided an adequate start-up package consisting of research funding, laboratory space, and one year of protected time from teaching responsibilities. Overall, reviewers felt that this was an intriguing and creative proposal from a promising new investigator. They commented that project is high-risk, but one that is worth an investment.